US 2011 0003295A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0003295 A1 Liew (43) Pub. Date: Jan. 6, 2011
(54) METHOD OF PROFILING GENE 7.598,031, which is a continuation of application No. EXPRESSION IN A SUBJECT UNDERGOING 09/477,148, filed on Jan. 4, 2000, now abandoned. A TREATMENT (60) Provisional application No. 60/115,125, filed on Jan. (75) Inventor: Choong-Chin Liew, Toronto (CA) 6, 1999. Correspondence Address: Publication Classification EDWARDS ANGELL PALMER & DODGE LLP (51) Int. Cl. P.O. BOX SS874 CI2O I/68 (2006.01) BOSTON, MA 02205 (US) GOIN 33/53 (2006.01) (52) U.S. Cl...... 435/6: 436/94 (73) Assignee: GENENEWS CORPORATION, Richmond Hill (CA) (57) ABSTRACT The present invention is directed to detection and measure (21) Appl. No.: 12/757,921 ment of gene transcripts in blood. Specifically provided is a RT-PCR analysis performed on a drop of blood for detecting, (22) Filed: Apr. 9, 2010 diagnosing and monitoring diseases using tissue-specific primers. The present invention also describes methods by Related U.S. Application Data which delineation of the sequence and/or quantitation of the (63) Continuation of application No. 12/587,384, filed on expression levels of disease-associated genes allows for an Oct. 6, 2009, which is a continuation of application immediate and accurate diagnostic/prognostic test for disease No. 10/268,730, filed on Oct. 9, 2002, now Pat. No. or to assess the effect of a particular treatment regimen.
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METHOD OF PROFILNG GENE blood in the diagnosis, prognosis and monitoring of genetic EXPRESSION IN A SUBJECT UNDERGOING and infectious disease in the human body. The process A TREATMENT described herein requires a simple blood sample and is, there fore, non-invasive compared to conventional practices used to CROSS-REFERENCE TO RELATED detect tissue specific disease, Such as biopsies. APPLICATION 0010. One object of the present invention is to provide a 0001. This application is a continuation of U.S. patent non-invasive method for the diagnosis, prognosis and moni application Ser. No. 12/587,384, filed Oct. 5, 2009, which is toring of genetic and infectious disease in humans and ani a continuation of U.S. patent application Ser. No. 10/268,730 mals. filed Oct. 9, 2002, now U.S. Pat. No. 7,598,031, which is a 0011. In one embodiment of the present invention, there is continuation of U.S. application Ser. No. 09/477,148 filed provided a method for detecting expression of a gene in blood Jan. 4, 2000, now abandoned, which claims the benefit of U.S. from a Subject, comprising the steps of: a) quantifying RNA Provisional Application No. 60/115,125 filed on Jan. 6, 1999. from a Subject blood sample; and b) detecting expression of Each of these applications is incorporated herein by reference the gene in the quantified RNA, wherein the expression of the in their entirety, including the figures and drawings. gene in quantified RNA indicates the expression of the gene in the subject blood. BACKGROUND OF THE INVENTION 0012. In another embodiment of the present invention, 0002 1. Field of the Invention there is provided a method for detecting expression of one or 0003. The present invention relates generally to the more genes in blood from a Subject, comprising the steps of molecular biology of human diseases. More specifically, the a) obtaining a subject blood sample; b) extracting RNA from present invention relates to a process using the genetic infor the blood sample; c) amplifying the RNA; d) generating mation contained in human peripheral whole blood for the expressed sequence tags (ESTs) from the amplified RNA diagnosis, prognosis and monitoring of genetic and infectious product; and e) detecting expression of the genes in the ESTs, disease in the human body. wherein the expression of the genes in the ESTs indicates the 0004 2. Description of the Related Art expression of the genes in the subject blood. Preferably, the 0005. The blood is a vital part of the human circulatory genes are tissue-specific genes. system for the human body. Numerous cell types make up the 0013 Instill another embodiment of the present invention, blood tissue including monocytes, leukocytes, lymphocytes there is provided a method for detecting expression of one or and erythrocytes. Although many blood cell types have been more genes in blood from a subject, comprising the steps of described, there are likely many as yet undiscovered cell a) obtaining a Subject blood sample; b) extracting DNA frag types in the human blood. Some of these undiscovered cells ments from the blood sample; c) amplifying the DNA frag may exist transiently, such as those derived from tissues and ments; and d) detecting expression of the genes in the ampli organs that are constantly interacting with the circulating fied DNA product, wherein the expression of the genes in the blood in health and disease. Thus, the blood can provide an amplified DNA product indicates the expression of the genes immediate picture of what is happening in the human body at in the subject blood. any given time. 0014. In yet another embodiment of the present invention, 0006. The turnover of cells in the hematopoietic system is there is provided a method for monitoring a course of a enormous. It was reported that over one trillion cells, includ therapeutic treatment in an individual, comprising the steps ing 200 billion erythrocytes and 70 billion neutrophilic leu of: a) obtaining a blood sample from the individual; b) kocytes, turn over each day in the human body (Ogawa 1993). extracting RNA from the blood sample; c) amplifying the As a consequence of continuous interactions between the RNA; d) generating expressed sequence tags (ESTs) from the blood and the body, genetic changes that occur within the amplified RNA product; e) detecting expression of genes in cells or tissues of the body will trigger specific changes in the ESTs, wherein the expression of the genes is associated gene expression within blood. It is the goal of the present with the effect of the therapeutic treatment; and f) repeating invention that these genetic alterations be harnessed for diag steps a)-e), wherein the course of the therapeutic treatment is nostic and prognostic purposes, which may lead to the devel monitored by detecting the change of expression of the genes opment of therapeutics for ameliorating disease. in the ESTs. Such a method may also be used for monitoring 0007. The complete profile of gene expression in the cir the onset of overt symptoms of a disease, wherein the expres culating blood remains totally unexplored. It is hypothesized sion of the genes is associated with the onset of the symptoms. that gene expression in the blood is reflective of body state 0015. In still yet another embodiment of the present inven and, as such, the resultant disruption of homeostasis under tion, there is provided a method for diagnosing a disease in a conditions of disease can be detected through analysis of test Subject, comprising the steps of: a) generating a cDNA transcripts differentially expressed in the blood alone. Thus, library for the disease from a whole blood sample from a the identification of several key transcripts or genetic markers normal Subject; b) generating expressed sequence tag (EST) in blood will provide information about the genetic state of profile from the normal subject clNA library; c) generating a the cells, tissues, organ systems of the human body in health cDNA library for the disease from a whole blood sample from and disease. a test subject; d) generating EST profile from the test subject 0008. The prior art is deficient in non-invasive methods of cDNA library; and e) comparing the test subject EST profile screening for tissue-specific diseases. The present invention to the normal subject EST profile, wherein if the test subject fulfills this long-standing need and desire in the art. EST profile differs from the normal subject EST profile, the test Subject might be diagnosed with the disease. SUMMARY OF THE INVENTION 0016. In still yet another embodiment of the present inven 0009. This present invention discloses a process of using tion, there is provided a kit for diagnosing, prognosing or the genetic information contained in human peripheral whole predicting a disease, comprising: a) gene-specific primers; US 2011/0003295 A1 Jan. 6, 2011 wherein the primers are designed in Such a way that their jects showed normal glucose tolerance, and the last Subject sequences contain the opposing ends of two adjacent exons had late onset diabetes type II. FIG. 5C shows standardized for the specific gene with the intron sequence excluded; and levels of insulin gene expressed in each fractionated cell from b) a carrier, wherein the carrier immobilizes the primer(s). whole blood. Such a kit may be applied to a test subject whole blood sample 0026 FIG. 6 shows the differential screening of human to diagnose, prognose or predict a disease. blood cell cDNA library with different cDNA probes of heart 0017. In yet another embodiment of the present invention, and brain tissue. FIG. 6A shows blood cell clNA probes vs. there is provided a kit for diagnosing, prognosing or predict adult heart cDNA probes. FIG. 6B shows blood cell cDNA ing a disease, comprising: a) probes derived from a whole probes vs. human brain cDNA probes. blood sample for a specific disease; and b) a carrier, wherein 0027 FIG. 7 graphically shows the 1,800 unique genes in the carrier immobilizes the probes. Such a kit may be applied human blood and in the human fetal heart grouped into seven to a test Subject whole blood sample to diagnose, prognose or cellular functions. predict a disease. 0018. Furthermore, the present invention provides a DETAILED DESCRIPTION OF THE INVENTION cDNA library specific for a disease, wherein the cDNA 0028. In accordance with the present invention, there may library is generated from whole blood samples. be employed conventional molecular biology, microbiology, 0019. Other and further aspects, features, and advantages and recombinant DNA techniques within the skill of the art. of the present invention will be apparent from the following Such techniques are explained fully in the literature. See, e.g., description of the presently preferred embodiments of the Sambrook, Fritsch & Maniatis, “Molecular Cloning: A Labo invention. These embodiments are given for the purpose of ratory Manual (1982): “DNA Cloning: A Practical disclosure. Approach.” Volumes I and II (D. N. Glovered. 1985): “Oli gonucleotide Synthesis” (M.J. Gaited. 1984); "Nucleic Acid BRIEF DESCRIPTION OF THE DRAWINGS Hybridization B. D. Hames & S. J. Higgins eds. (1985); 0020 So that the matter in which the above-recited fea “Transcription and Translation'B. D. Hames & S.J. Higgins tures, advantages and objects of the invention, as well as eds. (1984): “Animal Cell Culture R. I. Freshney, ed. others which will become clear, are attained and can be under (1986): “Immobilized Cells And Enzymes' IRL Press, stood in detail, more particular descriptions of the invention (1986); B. Perbal, “A Practical Guide To Molecular Clon briefly summarized above may be had by reference to certain ing' (1984). Therefore, if appearing herein, the following embodiments thereof which are illustrated in the appended terms shall have the definitions set out below. drawings. These drawings form a part of the specification. It (0029. A “cDNA” is defined as copy-DNA or complemen is to be noted, however, that the appended drawings illustrate tary-DNA, and is a product of a reverse transcription reaction preferred embodiments of the invention and therefore are not from an mRNA transcript. “RT-PCR refers to reverse tran to be considered limiting in their scope.not be considered to Scription polymerase chain reaction and results in production limit the scope of the invention. of cDNAs that are complementary to the mRNA template(s). 0021 FIG. 1 shows the following RNA samples prepared 0030 The term "oligonucleotide' is defined as a molecule from human blood; FIG. 1A: Lane 1, Molecular weight comprised of two or more deoxyribonucleotides, preferably marker; Lane 2, RT-PCR on APP gene; Lane 3, PCR on APP more than three. Its exact size will depend upon many factors gene; Lane 4, RT-PCR on APC gene; Lane 5, PCR on APC which, in turn, depend upon the ultimate function and use of gene: FIG. 1B: Lanes 1 and 2, RT-PCR and PCR of (MyHC, the oligonucleotide. The term “primer' as used herein refers respectively; Lanes 3 and 4, RT-PCR of (MyHC from RNA to an oligonucleotide, whether occurring naturally as in a prepared from human fetal and human adult heart, respec purified restriction digest or produced synthetically, which is tively; Lane 5, Molecular weight marker. capable of acting as a point of initiation of synthesis when 0022 FIG. 2 shows quantitative RT-PCR analysis per placed under conditions in which synthesis of a primer exten formed on RNA samples extracted from a drop of blood. sion product, which is complementary to a nucleic acid Forward primer (5'-GCCCTCTGGGGACCTGAC-3', SEQ Strand, is induced, i.e., in the presence of nucleotides and an ID No. 1) of exon 1 and reverse primer (5'-CCCACCTG inducing agent Such as a DNA polymerase and at a Suitable CAGGTCCTCT-3", SEQ ID No. 2) of exons 1 and 2 of temperature and pH. The primer may be either single insulin gene. Blood samples of 4 normal Subjects were stranded or double-stranded and must be sufficiently long to assayed. Lanes 1, 3, 5 and 7 represent overnight “fasting prime the synthesis of the desired extension product in the blood sample and lanes 2, 4, 6 and 8 represent “non-fasting presence of the inducing agent. The exact length of the primer samples. will depend upon many factors, including temperature, 0023 FIG. 3 shows quantitative RT-PCR analysis per source of primer and the method used. For example, for formed on RNA samples extracted from a drop of blood. diagnostic applications, depending on the complexity of the Lanes 1 and 2 represent normal healthy person and lane 3 target sequence, the oligonucleotide primer typically con represents late-onset diabetes (Type II) and lane 4 represents tains 15-25 or more nucleotides, although it may contain asymptomatic diabetes. fewer nucleotides. The factors involved in determining the 0024 FIG. 4 shows multiple RT-PCR assay in a drop of appropriate length of primer are readily known to one of blood. Primers were derived from insulin gene (INS), zinc ordinary skill in the art. finger protein gene (ZFP) and house-keeping gene (GADH). 0031. As used herein, random sequence primers refer to a Lane 1 represents normal person. Lane 2 represents late-onset composition of primers of random sequence, i.e. not directed diabetes and lane 3 represents asymptomatic diabetes. towards a specific sequence. These sequences possess Suffi 0025 FIG. 5 shows standardized levels of insulin gene cient complementary to hybridize with a polynucleotide and (FIG. 5A) and ZFP gene (FIG. 5B) expressed in a drop of the primer sequence need not reflect the exact sequence of the blood. The first three subjects were normal, second two sub template. US 2011/0003295 A1 Jan. 6, 2011
0032) “Restriction fragment length polymorphism” refers animal. The genes are non-cancer-associated and tissue-spe to variations in DNA sequence detected by variations in the cific genes. Still preferably, the amplification is performed by length of DNA fragments generated by restriction endonu RT-PCR using random sequence primers or gene-specific clease digestion. primers. 0033. A standard Northern blotassay can be used to ascer 0037. In still another embodiment of the present invention, tain the relative amounts of mRNA in a cellor tissue obtained there is provided a method for detecting expression of one or from plant or other tissue, in accordance with conventional more genes in blood from a Subject, comprising the steps of Northern hybridization techniques known to those persons of a) obtaining a Subject blood sample; b) extracting DNA frag ordinary skill in the art. The Northern blot uses a hybridiza ments from the blood sample; c) amplifying the DNA frag tion probe, e.g. radiolabelled cDNA, either containing the ments; and d) detecting expression of the genes in the ampli full-length, single stranded DNA or a fragment of that DNA fied DNA product, wherein the expression of the genes in the sequence at least 20 (preferably at least 30, more preferably at amplified DNA product indicates the expression of the genes least 50, and most preferably at least 100 consecutive nucle in the subject blood. otides in length). The DNA hybridization probe can be 0038. In yet another embodiment of the present invention, labelled by any of the many different methods known to those there is provided a method for monitoring a course of a skilled in this art. The labels most commonly employed for therapeutic treatment in an individual, comprising the steps these studies are radioactive elements, enzymes, chemicals of: a) obtaining a blood sample from the individual; b) which fluoresce when exposed to untraviolet light, and others. extracting RNA from the blood sample; c) amplifying the A number of fluorescent materials are known and can be RNA; d) generating expressed sequence tags (ESTs) from the utilized as labels. These include, for example, fluorescein, amplified RNA product; e) detecting expression of genes in rhodamine, auramine, Texas Red, AMCA blue and Lucifer the ESTs, wherein the expression of the genes is associated Yellow. A particular detecting material is anti-rabbitantibody with the effect of the therapeutic treatment; and f) repeating prepared in goats and conjugated with fluorescein through an steps a)-e), wherein the course of the therapeutic treatment is isothiocyanate. Proteins can also be labeled with a radioactive monitored by detecting the change of expression of the genes element or with an enzyme. The radioactive label can be in the ESTs. Such a method may also be used for monitoring detected by any of the currently available counting proce the onset of overt symptoms of a disease, wherein the expres dures. The preferred isotope may be selected from H, C, sion of the genes is associated with the onset of the symptoms. 32P 35S, 36C1, 5 Cr, 57Co, 58Co, 5°Fe, 90Y. 125I, 13 II, and Preferably, the amplification is performed by RT-PCR, and Re. Enzyme labels are likewise useful, and can be detected the change of the expression of the genes in the ESTs is by any of the presently utilized colorimetric, spectrophoto monitored by sequencing the ESTs and comparing the result metric, fluorospectrophotometric, amperometric or gasomet ing sequences at various time points; or by performing single ric techniques. The enzyme is conjugated to the selected nucleotide polymorphism analysis and detecting the variation particle by reaction with bridging molecules such as carbo of a single nucleotide in the ESTs at various time points. diimides, diisocyanates, glutaraldehyde and the like. Many 0039. In still yet another embodiment of the present inven enzymes which can be used in these procedures are known tion, there is provided a method for diagnosing a disease in a and can be utilized. The preferred are peroxidase, (-glucu test Subject, comprising the steps of: a) generating a cDNA ronidase, (-D-glucosidase, (-D-galactosidase, urease, glu library for the disease from a whole blood sample from a cose oxidase plus peroxidase and alkaline phosphatase. U.S. normal Subject; b) generating expressed sequence tag (EST) Pat. Nos. 3,654,090, 3,850,752, and 4,016,043 are referred to profile from the normal subject clNA library; c) generating a by way of example for their disclosure of alternate labeling cDNA library for the disease from a whole blood sample from material and methods. a test subject; d) generating EST profile from the test subject 0034. As used herein, “individual' refers to human sub cDNA library; and e) comparing the test subject EST profile jects as well as non-human Subjects. The examples herein are to the normal subject EST profile, wherein if the test subject not meant to limit the methodology of the present invention to EST profile differs from the normal subject EST profile, the human Subjects only, as the instant methodology is useful in test Subject might be diagnosed with the disease. the fields of Veterinary medicine, animal Sciences and such. 0040. In still yet another embodiment of the present inven 0035. In one embodiment of the present invention, there is tion, there is provided a kit for diagnosing, prognosing or provided a method for detecting expression of a gene in blood predicting a disease, comprising: a) gene-specific primers; from a subject, comprising the steps of: a) quantifying RNA wherein the primers are designed in Such a way that their from a subject blood sample; and b) detecting expression of sequences contain the opposing ends of two adjacent exons the gene in the quantified RNA, wherein the expression of the for the specific gene with the intron sequence excluded; and gene in quantified RNA indicates the expression of the gene in b) a carrier, wherein the carrier immobilizes the primer(s). the Subject blood. An example of the quantifying method is by Preferably, the gene-specific primers are selected from the mass spectrometry. group consisting of insulin-specific primers, atrial natriuretic 0036. In another embodiment of the present invention, factor-specific primers, Zinc finger protein gene-specific there is provided a method for detecting expression of one or primers, beta-myosin heavy chain gene-specific primers, more genes in blood from a Subject, comprising the steps of amyloid precurser protein gene-specific primers, and a) obtaining a subject blood sample; b) extracting RNA from adenomatous polyposis-coli protein gene-specific primers. the blood sample; c) amplifying the RNA; d) generating Further preferably, the gene-specific primers are selected expressed sequence tags (ESTs) from the amplified RNA from the group consisting of SEQID Nos. 1 and 2; and SEQ product; and e) detecting expression of the genes in the ESTs, ID Nos. 5 and 6. Such a kit may be applied to a test subject wherein the expression of the genes in the ESTs indicates the whole blood sample to diagnose, prognose or predict a dis expression of the genes in the subject blood. Preferably, the ease by detecting the quantitative expression levels of specific Subject is a fetus, an embryo, a child, an adult or a non-human genes associated with the disease in the test Subject and then US 2011/0003295 A1 Jan. 6, 2011 comparing to the levels of same genes expressed in a normal beta-myosin heavy chain gene ((MyHC), amyloid precurser Subject. Such a kit may also be used for monitoring a course protein (APP) gene and adenomatous polyposis-coli protein of therapeutic treatment or monitoring the onset of overt (APC) gene. The PCR products were also subjected to auto symptoms of a disease. mated DNA sequencing to Verify the sequences as derived 0041. In yet another embodiment of the present invention, from the specific transcripts of blood. there is provided a kit for diagnosing, prognosing or predict ing a disease, comprising: a) probes derived from a whole Example 5 blood sample for a specific disease; and b) a carrier, wherein the carrier immobilizes the probes. Such a kit may be applied Detection of Tissue Specific Gene Expression in to a test Subject whole blood sample to diagnose, prognose or Human Blood Using RT-PCR predict a disease by detecting the quantitative expression levels of specific genes associated with the disease in the test 0048. The beta-myosin heavy chain gene ((MyHC) tran Subject and then comparing to the levels of same genes script (mRNA) is known to be highly expressed in ventricles expressed in a normal Subject. Such a kit may also be used for of the human heart. This sarcomeric protein is important for monitoring a course of therapeutic treatment or monitoring heart muscle contraction and its presence would not be the onset of overt symptoms of a disease. expected in other non-muscle tissues and blood. In 1990, the 0042. Furthermore, the present invention provides a gene for human cardiac (MyHC was completely sequenced cDNA library specific for a disease, wherein the cDNA (Liew et al. 1990) and was comprised of 41 exons and 42 library is generated from whole blood samples. introns. 0043. The following examples are given for the purpose of 0049. The method of reverse transcription polymerase illustrating various embodiments of the invention and are not chain reaction (RT-PCR) was used to determine whether this meant to limit the present invention in any fashion. cardiac specific mRNA is also present in human blood. A pair of primers was designed; the forward primer (SEQID No. 3) Example 1 was on the boundary of exons 21 and 22, and the reverse primer (SEQID No. 4) was on the boundary of exons 24 and Construction of a cDNA Library 25. This region of mRNA is only present in (My HC and is not 0044 RNA extracted from human tissues (including fetal found in the alpha-myosin heavy chain gene ((MyHC). heart, adult heart, liver, brain, prostate gland and whole 0050. A blood sample was first treated with lysing buffer blood) were used to construct unidirectional cDNA libraries. and then undergone centrifuge. The resulting pellets were The first mammalian heart clNA library was constructed as further processed with RT-PCR. RT-PCR was performed early as 1982. Since then, the methodology has been revised using the total blood cell RNA as a template. A nested PCR and optimal conditions have been developed for construction product was generated and used for sequencing. The sequenc of human heart and hematopoietic progenitor cDNA libraries ing results were subjected to BLAST and the identity of exons (Liew et al., 1984; Liew 1993, Claudio et al., 1998). Most of 21 to 25 was confirmed to be from (MyHC (FIG. 1A). the novel genes which were identified by sequence annotation 0051. Using the same method just described, two other can now be obtained as full length transcripts. tissue specific genes—amyloid precursor protein (APP for ward primer, SEQID No. 7: reverse primer, SEQID No. 8) Example 2 found in the brain and associated with Alzheimer's disease, Catalogue of Blood Cell ESTs and adenomatous polyposis coli protein (APC) found in the colon and rectum and associated with colorectal cancer 0.045 Random partial sequencing of expressed sequence (Groden et al. 1991; Santoro and Groden 1997)—were also tags (ESTs) of cDNA clones from the blood cell library was detected in the RNA extracted from human blood (FIG. 1B). carried out to establish an EST database of blood. The known genes as derived from the ESTs were categorized into seven Example 6 major cellular functions (Hwang, Dempsey et al., 1997). Multiple RT-PCR Analysis on a Drop of Blood from Example 3 a Normal/Diseased Individual Differential Screening of cDNA Library 0052. A drop of blood was extracted to obtain RNA to 0046 cDNA probes generated from transcripts of each carry out quantitative RT-PCR analysis. Specific primers for tissue were used to hybridize the blood cell cDNA clones the insulin gene were designed: forward primer (5'-GC (Liew et al., 1997). The “positive' signals which were hybrid CCTCTGGGGACCTGAC-3', SEQID No. 1) of exon 1 and ized with P-labelled cDNA probes were defined as genes reverse primer (5'-CCCACCTGCAGGTCCTCT-3", SEQID which shared identity with blood and respective tissues. The No. 2) of exons 1 and 2 of insulin gene. Such reverse primer “negative spots which were not exposed to P-labelled cDNA was obtained by deleting the intron between the exons 1 and probes were considered to be blood-cell-enriched or low fre 2. Blood samples of 4 normal Subjects were assayed. It was quency transcripts. found that the insulin gene is expressed in the blood and the quantitative expression of the insulin gene in a drop of blood Example 4 is influenced by fasting and non-fasting states of normal healthy subjects (FIG. 2). This very low level of expression of Reverse Transcriptase-Polymerase Chain Reaction the insulin gene reflects the phenotypic status of a person and (RT-PCR) Assay strongly suggests that there is a physiological and pathologi 0047 RNA extracted from samples of human tissue was cal role for its expression, contrary to the basal or illegitimate used for RT-PCR analysis (Jin et al. 1990). Three pairs of theory of transcription suggested by Chelly et al. (1989) and forward and reverse primers were designed for human cardiac Kimoto (1998). US 2011/0003295 A1 Jan. 6, 2011
0053 Same quantitative RT-PCR analysis was performed together with the seven cellular functions related to percent using insulin specific primers on RNA samples extracted distribution of known genes in blood and in the fetal heart. from a drop of blood from a normal healthy person, a person 0060. From 20,000 ESTs, 1,800 have been identified as having late-onset diabetes (Type II) and a person having known genes which may not all appear in the hemapoietic asymptomatic diabetes. It was found that the insulin gene is system. For example, the insulin gene and the atrial natri expressed differentially amongst Subjects that are healthy, uretic factor gene have not been detected in these 20,000 diagnosed as type II diabetic, and also in an asymptomatic ESTs but their transcripts were detected in a drop of blood, preclinical patient (FIG. 3). strongly suggesting that all transcripts of the human genome 0054 Similarly, specific primers for the atrial natriuretic can be detected by performing RT-PCR analysis on a drop of factor (ANF) gene were designed (forward primer, SEQ ID blood. No. 5; reverse primer, SEQID No. 6) and RT-PCR analysis 0061. In addition, approximately 400 novel genes have was performed on a drop of blood. ANF is known to be highly been identified from the 20,000 ESTs characterized to date, expressed in heart tissue biopsies and in the plasma of heart and these will be subjected to full length sequencing and open failure patients. However, atrial natriuretic factor was reading frame alignment to reduce the actual number of novel observed to be expressed in the blood and the expression of ESTs prior to screening for disease markers. the atrial natriuretic factor gene is significantly higher in the 0062 Analysis of the approximately 6,283 ESTs which blood of patients with heart failure as compared to the blood have known matches in the GenBank databases revealed that of a normal control patient. this dataset represents over 1,800 unique genes. These genes 0055 Specific primers for the zinc finger protein gene have been catalogued into seven cellular functions. Compari (ZFP forward primer, SEQID No. 9; reverse primer, SEQID sons of this set of unique genes with ESTs derived from No. 10) were also designed and RT-PCR analysis was per human brain, heart, lung and kidney demonstrated a greater formed on a drop of blood. ZFP is known to be high in heart than 50% overlap in expression (Table 1). tissue biopsies of cardiac hypertrophy and heart failure patients. In the present study, the expression of ZFP was TABLE 1 observed in the blood as well as differential expression levels of ZFP amongst the normal, diabetic and asymptomatic pre Overlap of Genes Expressed in Blood clinical subjects (FIG. 4); although neither of the non-normal Tissues ESTs 8:8 Overlap in Blood Subjects has been specifically diagnosed as Suffering from brain 134,000 60% cardiac hypertrophy and/or heart failure, the higher expres heart 65,000 5.99% sion levels of the ZFP gene in their blood may indicate that lung 60,200 S8% these subjects are headed in that general direction. kidney 32,300 54% 0056. It was hypothesized that a housekeeping gene such * Estimated from limited known genes of about 1,800 as derived from the database of 6,297 as glyceraldehyde dehydrogenase (GADH) which is required ESTs from human blood cell library, and highly expressed in all cells would not be differentially **Obtained from the National Centre of Biotechnology Information (NCBI), U.S.A. expressed in the blood of normal vs. disease subjects. This hypothesis was confirmed by RT-PCR using GADH specific Example 8 primers (FIG. 4). Thus, GADH is useful as an internal control. 0057 Standardized levels of insulin gene or ZFP gene Blood Cell ESTS expressed in a drop of blood were estimated using a house 0063. The results from the differential screening clearly keeping gene as an internal control relative to insulin or ZFP indicate that the transcripts expressed in the whole blood are expressed (FIGS. 5A & 5B). The levels of insulin gene reflective of genes expressed in all cells and tissues of the expressed in each fractionated cell from whole blood were body. More than 95% of detectable spots were identical from also standardized and shown in FIG. 5C. two different tissues. The remaining 5% of spots may repre sent cell- or tissue-specific transcripts; however, results Example 7 obtained from partial sequencing to generate ESTs of these clones revealed most of them not to be cell- or tissue-specific Human Blood Cell cDNA Library transcripts. Therefore, the negative spots are postulated to be reflective of low abundance transcripts in the tissue from 0058. In order to further substantiate the present invention, which the cDNA probes were derived. differential screening of the human blood cell cDNA library 0064. An alternative approach that was employed to iden was conducted. cDNA probes derived from human blood, tify transcripts expressed at low levels is the large-scale gen adult heart or brain were respectively hybridized to the human eration of expressed sequence tags (ESTs). There is substan blood cDNA library clones. As shown in FIG. 7, more than tial evidence regarding the efficiency of this technology to 95% of the “positively' identified clones are identical detect previously characterized (known) and uncharacterized between the blood and other tissue samples. (unknown or novel) genes expressed in the cardiovascular 0059 DNA sequencing of randomly selected clones from system (Hwang & Dempsey et al. 1997). In the present inven the human whole blood cell cloNA library was also per tion, 20,000 ESTs have been produced from a human blood formed. This allowed information regarding the cellular func cell cDNA library and resulted in the identification of tion of blood to be obtained concurrently with gene identifi approximately 1,800 unique known genes (Table 2) cation. More than 20,000 expressed sequence tags (ESTs) 0065. In the most recent GenBank release, analysis of have been generated and characterized to date, 17.6% of more than 300,000 ESTs in the database (dbESTs) generated which did not result in a statistically significant match to more than 48,000 gene clusters which are thought to represent entries in the GenBank databases and thus were designated as approximately 50% of the genes in the human genome. Only “Novel ESTs. These results are Summarized in FIG. 7 4,800 of the dbPSTs are blood-derived. In the present inven US 2011/0003295 A1 Jan. 6, 2011
tion, 20,000 ESTs have been obtained to date from a human the limited set of 1,000 ESTs, there are at least 200 known blood cDNA library, which provides the world's most infor genes that are shared with other tissue related genes (Claudio mative database with respect to blood cell transcripts. From et al. 1998). the limited amount of information generated so far (i.e. 1,800 unique genes), it has already been determined that more than 0067 Table 2 demonstrates the expression of known genes 50% of the transcripts are found in other cells or tissues of the of specific tissues in blood cells. Previously, only the presence human body (Table 2). Thus, it is expected that by increasing of “housekeeping genes would have been expected. Addi the number of ESTs generated, more genes will be identified tionally, the presence of at least 25 of the currently known 500 that have an overlap in expression between the blood and genes corresponding to molecular drug targets was detected. other tissues. Furthermore, the transcripts for several genes These molecular drug targets are used in the treatment of a which are known to have tissue-restricted patterns of expres variety of diseases which involve inflammation, renal and sion (i.e. (MyHC, APP. APC, ANF, ZFP) have also been cardiovascular function, neoplastic disease, immunomodula demonstrated to be present in blood. tion and viral infection (Drews & Ryser, 1997). It is expected 0066 Most recently, a cDNA library of human hemato that additional novel ESTs will represent future molecular poietic progenitor stem cells has also been constructed. From drug targets.
TABLE 2 Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
100 kDa coactivator 2 U22055 -- -- 10 kD protein (BC10) 2 AFOS3470 ------14-3-3 epsilon 2 U54778 ------14-3-3 protein 11 U28964 ------15 kDa selenoprotein (SEP15) 1 AFOS1894 ------1-phosphatidylinositol-4- 1 S78798 phosphate 5-kinase isoform C 23 kD highly basic protein 21 XS 6932 ------2-5A-dependent RNase 1 L10381 2'-5'oligoadenylate synthetase 4 M87284 B 2 (OAS2) 26S proteasome subunit 11 1 AFO86708 36 kDa phosphothyrosine 2 A.22328O T -- protein 3-7 gene product (non-exact 1 D64159 86% aa) 3-phosphoglycerate 1 AFOO6O43 T ------dehydrogenase (PGAD) 3-prime-phosphoadenosine 5- 2 US3447 ------prime-phosphosulfate synthase 1 (PAPSS1) 46 kd mannose 6-phosphate 1 X56257 receptor (MPR46) (low match) 5-aminoimidazole-4- 1 D89976 carboxamide ribonucleotide transformylase 5'-nucleotidase 3 D38524 T -- -- 6-phosphofructo-2- 1 D498.18 -- kinase? fructose-2,6- biphosphatase 4 (PFKFB4) 6-phosphofructo-2- 1 AFO41829 kinase? fructose-2,6- bisphosphatase (PF2K) 71 kd heat shock cognate 23 YOO371 protein hsc70 76 kDa membrane protein 2 ------(P76) 8-oxoguanine DNA 1 U96710 B -- -- glycosylase (OGG1) a disintegrin and 1 AFOO961S T -- metalloprotease domain 10 (ADAM10) a disintegrin and 1 D265.79 B -- metalloprotease domain 8 (ADAM8) A kinase anchor protein 95 2 Y11997 B, Tactivated -- -- (AKAP95) Akinase anchor protein, 2 X97335 ------149 kD (AKAP149) US 2011/0003295 A1 Jan. 6, 2011
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu A4 differentiation-dependent 1 US3305 protein (A4), triple LIM domain protein (LMO6), and synaptophysin (SYP); calcium channel alpha-1 subunit (CACNA1F) ABL and putative M8604 Met 1 UO7561 protein Absent in melanoma 1 1 U83115 ------(AIM1) accessory proteins 2 Z31696 -- -- BAP31/BAP29 (DXS1357E) acetyl-Coenzyme A 2 X12966 ------acyltransferase (peroxisomal 3-oxoacyl-Coenzyme A thiolase) (ACAA) acetyl-Coenzyme A 1 D881.52 T lymphoma -- -- transporter (ACATN) acidic 82 kDa protein 4 U15552 acidic protein rich in leucines 1 YO7969 B ------(SSP29) Aconitase 2, mitochondrial 1 U8004O ------(ACO2) actin binding protein 1 AFOS9569 MAYVEN actin, beta (ACTB) 158 XO4098 T, B ------actin, beta (ACTB) (non- 1 M10277 exact, low match 73%) actin, gamma (low score) 1 KOO791 actin, gamma 1 (ACTG 1) 4 XO4O98 ------+ high in many libraries actin-binding LIM protein 4 D31883 ------(ABLIM) Actinin, alpha 1 (ACTN1) 8 M95178 ------actinin, alpha 4 (ACTN4) 1 D8998O ------activated p21cdc42Hs kinase 1 L13738 B -- -- (ACK) activated RNA polymerase II 1 X798.05 ------transcription cofactor 4 (PC4) activating transcription factor 1 XSSS44 -- 1 (ATF1) activating transcription factor 1 X15875 ------2 (ATF2) activating transcription factor 2 M86842 -- -- 4 (tax-responsive enhancer element B67) (ATF4) active BCR-related gene 1 UO1147 ------(ABR) acyl-CoA oxidase (AOX) 1 UO3254 acyl-Coenzyme A 2 M16827 dehydrogenase, C-4 to C-12 straight chain (ACADM) acyl-Coenzyme A 3 D43682 ------dehydrogenase, very long chain (ACADVL) acyloxyacylhydrolase 3 M62840 T ------(neutrophil) (AOAH) adaptin, delta (ADTD) 2 U91930 ------adaptin, delta (ADTD) (non- 1 ACOOS328 exact 59%) adaptin, gamma (ADTG) 1 Y12226 ------adaptor complex sigma3B 2 X99459 ------(AP3S3) adaptor protein p150 1 YO8991 adducin 1 (alpha) (ADD1) 2 LO7261 ------adducin 1 (alpha) (add1) 3 L29296 ------adducin 3 (gamma) (ADD3) 3 U37122 B, W ------US 2011/0003295 A1 Jan. 6, 2011
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu adenine nucleotide 2 MS7424 ------translocator 2 (fibroblast) (ANT2) adenine nucleotide 1 JO2683 translocator 2 (fibroblast) (ANT2) (non-exact 81%) adenine nucleotide 1 JO2683 translocator 2 (fibroblast) (ANT2) (non-exact, 79%) adenine nucleotide 1 JO2683 translocator 2 (fibroblast) (ANT2) (non-exact, 86%) adenine nucleotide 3 JO3592 ------translocator 3 (liver) (ANT3) adenosine deaminase, RNA- 6 U18121 ------specific (ADAR) adenylate cyclase 3 (ADCY3) 2 AFO33861 ------adenylate cyclase 7 (ADCY7) 1 D25.538 adenylate kinase 2 (AK2) 2 U399.45 ------adenylate kinase 3 (AK3) 1 X60673 (non-exact, 67%) adenylyl cyclase-associated 28 M98474 T -- -- protein (CAP) adipose differentiation-related 1 X97324 ------protein; adipophilin (ADFP) ADP-ribosylation factor 1 13 M84326 ------(ARF1) ADP-ribosylation factor 3 2 M33384 ------(ARF3) ADP-ribosylation factor 4 1 M36341 T lymphoma ------(ARF4) ADP-ribosylation factor 5 1 M57567 ------(ARF5) ADP-ribosylation factor 1 LO4S10 -- domain protein 1, 64 kD (ARFD1) ADP-ribosyltransferase 4 M32721 ------(NAD+: poly (ADP-ribose) polymerase) (ADPRT) adrenergic, beta, receptor 2 X61157 B -- -- kinase 1 (ADRBK1) adrenoleukodystrophy-like 1 1 AJOOO327 (ALDL1) AE-binding protein 1 1 D864.79 (AEBP1) (non-exact, 62%) AF-17 1 UO7932 A-gamma-globin 1 WOOS14 A-gamma-globin 1 JOO176 (chromosome 11 allele) agammaglobulinaemia 1 UT8027 tyrosine kinase (ATK) AHNAKnucleoprotein 4 M8O899 ------(desmoyokin) (AHNAK) alanyl (membrane) 1 X13276 -- -- aminopeptidase (aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p.150) (ANPEP) alcohol dehydrogenase 5 1 M298.72 (class III), chi polypeptide (ADH5) aldehyde dehydrogenase 1, 1 AFOO3341 ------soluble (ALDH1) aldehyde dehydrogenase 10 2 UT5286 (fatty aldehyde dehydrogenase) (ALDH10) aldehyde reductase 1 (low Km 3 JO4795 B ------aldose reductase) (ALDR1) US 2011/0003295 A1 Jan. 6, 2011
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu aldo-keto reductase family 1, 2 JO4794 B ------member A1 (aldehyde reductase) (AKR1A1) aldo-keto reductase family 1, 1 D17793 ------member C3 (3-alpha hydroxysteroid dehydrogenase, type II) (AKR1C3) aldo-keto reductase family 7, 1 Y16675 ------member A2 (aflatoxin aldehyde reductase) (AKR7A2) aldolase A, fructose- 7 X12447 ------bisphosphate (ALDOA) aldolase C, fructose- 2 XOS196 ------bisphosphate (ALDOC) alkaline phosphatase, 45O2O62 liver bone/kidney (ALPL) ALL-1 (=L04731; L04284 4 Z6978O HRX) alpha mannosidase II isozyme DSS649 -- -- alpha thalassemiamental 3 UT5653 ------retardation syndrome X linked (ATRX) alpha-2 macroglobulin Z11711 alpha-2-globin 2 VOOS16 alpha-2-macroglobulin UO6985 receptor lipoprotein receptor protein (A2MR/LRP) alpha-polypeptide of N-acetyl- M13520 alpha-glucosaminidase (HEXA) alpha-spectrin X86901 alpha-subunit of Gi2a (GTP- XO7854 binding signal transduction protein) aminin receptor 1 (67kD); 2 JO3799 T ------Ribosomal protein SA (LAMR1) aminolevulinate, delta-, 1 X64467 -- dehydratase (ALAD) amino-terminal enhancer of 2 X73358 ------split (AES) amino-terminal enhancer of 3 UO4241 B ------split (AES) AMP deaminase isoform L 8 M91029 -- -- (AMPD2) amphiphysin (Stiff-Mann 1 UO7616 B -- -- syndrome with breast cancer 128 kD autoantigen) (AMPH) amphiphysin (Stiff-Mann 1 UO7616 syndrome with breast cancer 128 kD autoantigen) (AMPH) (non-exact, 68%) amphiphysin (Stiff-Mann 1 UO7616 syndrome with breast cancer 128 kD autoantigen) (AMPH) (non-exact, 68%) amphiphysin II 4 U87558 ------amphiphysin II (67% aa 1 AFO6891S amphiphysin?) amphiphysin II (non-exact 1 AFOO1383 69% aa) amphiphysin-like (AMPHL) 1 U684-85 -- -- amphiphysin-like (AMPHL) 1 AFO68918 (low match) US 2011/0003295 A1 Jan. 6, 2011 10
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
AMY1 1 DSO692 B, T -- amyloid beta (A4) precursor 1 L77864 ------protein-binding, family B, member 1 (Fe(55) (APBB1) amyloid beta (A4) precursor- 6 L27631 T lymphoma ------like protein 2 (APLP2) ankyrin 3, node of Ranvier U4396S (ankyrin G) (ANK) (non exact, 50%) annexin I (lipocortin I) XO5908 ------(ANX1) annexin II D28.364 annexin II (lipocortin II; 7 DOOO17 ------+ high in many libraries calpactin I, heavy polypeptide) (ANX2) annexin IV (placental M19383 ------anticoagulant protein II) (ANX4) annexin V (endonexin II) 2 M21731 ------(ANX5) annexin V (endonexin II) M19384 ------(ANXV) annexin VI (p68) (ANX6) 6 YOOO97 ------annexin VII (synexin) JO4S43 ------(ANX7) antigen identified by 2 M16279 ------monoclonal antibodies 12E7, F21 and O13 (MIC2) antigen identified by 3 JO2939 ------monoclonal antibodies 4F2, TRA1.10, TROP4, and T43 (MDU1) antigen TQ1 1 anti-oxidant protein 2 (non- 1 D14662 ------Selenium glutathione peroxidase, acidic calcium independent phospholipase A2) (KIAAO106) APEX nuclease S X66133 ------(multifunctional DNA repair enzyme) (APEX) Apollipoprotein L (APOL) 1 Z82215 (59% aa) apoptosis inhibitor 1 (API1) 1 L49431 ------apoptosis inhibitor 4 1 UT5285 B, W ------(survivin) (API4) apoptosis inhibitor 5 (API5) 1 U83857 T lymphoma -- -- apoptosis specific protein 1 Y11588 B ------(ASP) apoptotic protease activating 1 AFO13263 B ------factor (APAF1) aquaporin 3 (AQP3) 1 ABOO1325 T -- aquaporin 9 (AQP9) 7 AB008775 Tactivated -- arachidonate 12-lipoxygenase 1 MS8704 T -- -- (ALOX12) arachidonate 5-lipoxygenase- 3 X52195 ------activating protein (ALOX5AP) ariadne homolog (ARI) 1 AJOO9771 ------ariadne-2 (D. melanogaster) 1 AFO99149 ------homolog (all-trans retinoic acid inducible RING finger) (ARI2) ARP1 (actin-related protein 1, 1 X822O6 -- -- yeast) homolog A (centractin alpha) (ACTR1A) ARP2 (actin-related protein 2, 9 AFOO6082 ------yeast) homolog (ACTR2) US 2011/0003295 A1 Jan. 6, 2011 11
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu ARP2/3 protein compex S AFOO6085 Tactivated, W ------subunit 34 (ARC34) Arp2/3 protein compex 6 AF006084 monocyte ------subunit p41 (ARC41) stimulated Arp2/3 protein compex 1 AFOO6084 subunit p41 (ARC41)) (low match) Arp2/3 protein complex 20 AFO17807 ------subunit p16 (ARC16) Arp2/3 protein complex 2 AFOO6087 ------subunit p20 (ARC20) Arp2/3 protein complex 3 AFOO6086 W -- -- subunit p21(ARC21) ARP3 (actin-related protein 3, 11 AFOO6083 W ------yeast) homolog (ACTR3) arrestin, beta 2 (ARRB2) 1 AF106941 B, T, W ------arSA (bacterial) arsenite 1 AFO47469 B, T -- -- transporter, ATP-binding, homolog 1 (ASNA1) aryl hydrocarbon receptor 2 AFO44288 B ------nuclear translocator-like (ARNTL) aryl hydrocarbon receptor- U31913 ------interacting protein (AIP) arylsulfatase A (ARSA) X521.51 Tactivated -- -- asialoglycoprotein receptor 2 M11025 -- -- (ASGR2) asparaginyl-tRNA synthetase 3 D84273 ------(NARS) aspartyl-tRNA synthetase JOSO32 B ------(DARS) ataxiatelangiectasia mutated U82828 B, T -- -- (includes complementation groups A, C and D) (ATM) ataxin-2-like protein A2LP AFO34373 B, Tactivated ------(A2LG) ATF6 AFOOS887 -- -- ATP binding cassette U88667 transporter (ABCR) (non exact 80%) ATP synthase (F1-ATPase) XS9066 alpha subunit, mitochondrial ATP synthase beta subunit M19482 gene ATP synthase, H+ X60221 ------transporting, mitochondrial FO complex, Subunit b, isoform 1 (ATP5F1) ATP synthase, H+ X69907 Tactivated ------transporting, mitochondrial FO complex, Subunit c (Subunit 9), isoform 1 (ATP5G 1) ATP synthase, H+ 3 D14710 transporting, mitochondrial F1 complex, alpha Subunit, isoform 1, cardiac muscle (ATP5A1) ATP synthase, H+ 1 D14710 transporting, mitochondrial F1 complex, alpha Subunit, isoform 1, cardiac muscle (ATP5A1) (low match) ATP synthase, H+ 2 M27132 transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) US 2011/0003295 A1 Jan. 6, 2011 12
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
ATP synthase, H+ 1 D16563 W ------transporting, mitochondrial F1 complex, gamma polypeptide 1 (ATP5C1) ATP synthase, H+ 1 AFO92124 ------transporting, mitochondrial F1F0, subunit g (ATP5JG) ATP/GTP-binding protein 2 UT 3524 ------(HEAB) ATPase, Ca++ transporting, S Z69881 -- ubiquitous (ATP2A3) ATPase, H+ transporting, 2 D89052 ------ysosomal (vacuolar proton pump) 21 kD (ATP6F) ATPase, H+ transporting, 1 X76228 ------ysosomal (vacuolar proton pump) 31 kD (ATP6E) ATPase, H+ transporting, S X691.51 ------ysosomal (vacuolar proton pump) 42 kD; Vacuolar proton-ATPase, subunit C; V-ATPase, subunit C (ATP6D) ATPase, H+ transporting, 3 LO9235 -- -- ysosomal (vacuolar proton pump), alpha polypeptide, 70 kD, isoform 1 (ATP6A1) ATPase, H+ transporting, 6 X62949 ------ysosomal (vacuolar proton pump), beta polypeptide, 56/58 kD, isoform 2 ATPase, H+ transporting, 2 AFO38954 ------+ high in testis ysosomal (vacuolar proton pump), member J (ATP6J) ATPase, H+ transporting, D16469 ------ysosomal (vacuolar proton pump), subunit 1 (ATP6S1) ATP-binding cassette 50 AFO273O2 ------(TNF-alpha stimulated) (ABC50) ATP-binding cassette protein AFO47690 M-ABC1 (mitochondrial) ATP-dependent RNA helicase AJO10840 T lymphoma -- -- autoantigen (Hs.75528) 2 LOS425 Tactivated -- autoantigen (Hs.75528) (non- LOS425 exact 84%) autoantigen (Hs.75682) U17474 B -- -- autoantigen La SS-B Z35127 axin (AXIN1) AFOO9674 T -- axonemal dynein heavy chain AJOOOS22 -- (DNAH17) BAI1-associated protein 3 ABO17111 (BAIAP3) (non-exact 54%) basement membrane-induced AFO44896 gene (ICB1) basic leucine Zipper nuclear 2 UT9751 factor 1 (JEM-1) (BLZF1) basic transcription factor 3 5 X74O70 ------(BTF3) basigin (BSG) 1 L10240 -- -- BC-2 1 AFO42384 B ------B-cell CLLlymphoma 6 (zinc 1 UOO115 -- -- finger protein 51) (BCL6) B-cell translocation gene 1, 1 X61123 -- -- anti-proliferative (BTG) BCL2 adenovirus E1B 19 kD- 1 U15173 B ------interacting protein 2 (BNIP2) US 2011/0003295 A1 Jan. 6, 2011 13
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
BCL2 adenovirus E1B 19 kD 2 AFO67396 ------interacting protein 3-like (BNIP3L) beclin 1 (coiled-coil, myosin -- ike BCL2-interacting protein) (BECN1) beta-1,2-N- U15128 acetylglucosaminyltransferase I (MGAT2) beta-2-microglobulin (B2M) 63 S82297 ------high in invasive prostate tumor beta-hexosaminidase alpha M16411 chain (HEXA) beta-tubulin VOO599 ------high in many libraries beta-tubulin (non-exact, 76%) AFO70S61 beta-tubulin, pseudogene JOO315 BING4 Z971.84 biotinidase (BTD) (non-eact UO3274 62%) biotinidase (BTD) (non-exact UO3274 70%) biotinidase (BTD) (non-exact, UO3274 56%) BIOTINIDASE P43251 PRECURSOR biphenyl hydrolase-like X81372 -- (serine hydrolase) (BPHL) bone marrow stromal cell D21878 -- antigen 1 (BST1) box-dependent myc AFO43900 interacting protein isoform BIN1-10 (BIN1) box-dependent myc AFO43900 interacting protein isoform BIN1-10 (BIN1) (non-exact, 64%) brain myO47 protein AFO636OS T -- branched chain keto acid Z14093 T : : -- dehydrogenase E1, alpha polypeptide (maple syrup urine disease) (BCKDHA) BRCA1 associated protein-1 D87462 -- -- (ubiquitin carboxy-terminal hydrolase) (BAP1) BRCA1, Rho7 and vatl genes, L78833 and ipf35 breakpoint cluster region AFO44773 protein, uterine leiomyoma, 1: barrier to autointegration actor (BCRP1) breakpoint cluster region AFO44774 -- protein, uterine leiomyoma, 2 (BCRP2) breast cancer anti-estrogen U92715 resistance 3 (BCAR3) (non exact 73%) bromodomain-containing M91585 protein, 140 kD (peregrin) (BR140) Bruton's agammaglobulinemia U13424 tyrosine kinase (Btk) Bruton's tyrosine kinase (BTK) Bruton's tyrosine kinase (BTK), alpha-D-galactosidase A (GLA), L44-like ribosomal protein (L44L) and FTP3 (FTP3) US 2011/0003295 A1 Jan. 6, 2011 14
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
BS4 1 AF108083 BTG2 (BTG2) 6 YO9943 ------BTK region clone ftp 1 UT8027 ------BTK region clone flip-3 1 UO1923 ------BUB3 (budding uninhibited 4 AFOS3304 ------by benzimidazoles 3, yeast) homolog (BUB3) butyrate response factor 1 4 X79067 ------(EGF-response factor 1) (BRF1) butyrophilin (BTF1) 7 U90543 ------butyrophilin like receptor 1 ABO2O625.1 CAG repeat containing 2 U80744 -- -- (CTG4A) CAGH32 2 U80743 ------calcium channel, voltage- 1 M83566 dependent, L type, alpha 1D subunit (CACNA1D) (low match) calcium calmodulin- 1 AF069765 ------dependent protein kinase (CaM kinase) II gamma (CAMK2G) calcium calmodulin- 1 AF101.264 B ------dependent protein kinase kinase (KIAAO787) calmodulin (=M19311) 7 D45887 calmodulin 1 (phosphorylase 6 M27319 B ------kinase, delta) (CALM1) calnexin (CANX) 3 M948S9 T ------calpain, large polypeptide L1 S XO4366 ------(CAPN1) calpain, large polypeptide L2 S M23254 -- -- (CANP2) calpain, Small polypeptide 1 XO4106 ------(CAPN4) calpastatin (CAST) 3 D16217 -- Calponin 2 2 D83735 ------calponin 2 (CNN2) 1 D83735 B, T -- -- calponin 2 (CNN2) (low 1 D83735 score) calumenin (CALU) 3 AFO137.59 B ------cAMP response element- 4 LOS912 binding protein CRE-Bpa (H GS165L15.1) cAMP-dependent protein 1 M90360 kinase type II (Ht:31) canicular multispecific 1 AFOO967O ------organic anion transporter (CMOAT2) capping protein (actin 6 US 6637 B, T -- -- filament) muscle Z-line, alpha 1 (CAPZA1) capping protein (actin 2 UO3269 B -- -- filament) muscle Z-line, alpha 2 (CAPZA2) capping protein (actin 1 UO3271 ------filament) muscle Z-line, beta (CAPZB) capping protein (actin 8 M94345 ------filament), gelsolin-like (CAPG) carbamoyl-phosphate 1 D78586 ------synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) carbonic anhydrase V. 1 L19297 -- -- mitochondrial (CA5) US 2011/0003295 A1 Jan. 6, 2011 15
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu carboxypeptidase D (CPD) 3 U6SO90 B -- -- carnitine acylcarnitine 1 Y103.19 ------translocase (CACT) Cas-Br-M (murine) ecotropic 2 X571 10 -- retroviral transforming sequence (cbl) casein kinase 1, alpha 1 1 L37042 ------(CSNK1A1) casein kinase 2, alpha 1 2 M55265 B ------polypeptide (CSNK2A1) casein kinase I gamma 3L 1 AFO49090.1 (CSNK1G3L) casein kinase II alpha 1 X69951 subunit(=S72393) CASP8 and FADD-like 4 AFO15450 ------apoptosis regulator (CFLAR) caspase 1, apoptosis-relate 7 U13697 -- -- cysteine protease (interleukin 1, beta, convertase) (CASP1) caspase 10, apoptosis-related 1 U60519 B, T -- cysteine proteas (CASP10) activated, T lymphoma caspase 3, apoptosis-relate 3 U13737 B, T ------cysteine protease (CASP3) caspase 4, apoptosis-relate 6 U2S804 ------cysteine protease (CASP4) caspase 5, apoptosis-relate 1 U28O15 -- cysteine protease (CASP5) caspase 8, apoptosis-relate 2 X981.73 ------cysteine protease (CASP8) caspase 9, apoptosis-relate 1 US 6390 B -- -- cysteine protease (CASP9) catalase (CAT) S XO4O76 B ------catechol-O-methyltransferase 1 M65213 ------(COMT) catenin (cadherin-associated 6 D14705 -- -- protein), alpha 1 (102 kD) (CTNNA1) cathelicidin antimicrobial 1 X89658 B peptide (CAMP) cathepsin B (CTSB) 4 L1651O ------cathepsin C (CTSC) 3 UT9415 ------cathepsin D (lysosomal 4 M11233 ------aspartyl protease) (CTSD) cathepsin E (CTSE) 1 JOSO36 -- cathepsin G (CTSG) 1 M16117 T, W -- cathepsin S (CTSS) 34 M86553 B, Monocyte -- -- stimulated, T lymphoma cathepsin W (lymphopain) 4 AFO13611 -- (CTSW) CBF1 interacting corepressor 1 AFO98.297 CIR (=UO3644 recepin) CCAAT enhancer binding 3 X87248 ------protein (C/EBP), alpha (CEBPA) CCAAT enhancer binding 1 S631.68 ------protein (C/EBP), delta (CEBPB) CCAAT-box-binding 2 M371.97 T lymphoma -- -- transcription factor (CBF2) CCR5 receptor (CCR5) (non- 1 AFO11504 exact?) CD14 antigen (CD14) 11 M86S11 ------CD18 (=M95293) 4 X64071 CD1C antigen, c polypeptide 2 M28827 -- US 2011/0003295 A1 Jan. 6, 2011 16
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu CD2 antigen (cytoplasmic 1 AF104222 tail)-binding protein 2 (CD2BP2) CD2 antigen (p50), sheep red 4 M14362 ------blood cell receptor (CD2) CD2 cytoplasmic tail-binding 2 AFO386O2 -- protein 1 (CD2BP1) CD20 antigen (CD20) X12S30 CD20 receptor (S7) XO72O3 CD22 antigen (CD22) U62631 B CD24 signal transducer MS8664 CD33 antigen (gp67) (CD33) M231.97 -- CD33 antigen-like 2: OB U71383 binding protein-2 (CD33L2) (non-exact, 68%) CD33L2 (61% aa) D86359 CD36 antigen (collagen type I 7 M98398 T lymphoma ------receptor, thrombospondin receptor) (CD36) CD37 antigen (CD37) 5 X14046 ------CD38 at D84277 CD39 antigen (CD39) U87967 B ------CD3D antigen, delta XO3934 ------polypeptide (TIT3 complex) (CD3D) CD3E antigen, epsilon XO3884 -- -- polypeptide (TIT3 complex) (CD3E) CD3G antigen, gamma 2 XO6026 W -- polypeptide (TIT3 complex) (CD3G) CD37, antigen, Zeta 2 JO4132 -- -- polypeptide (TIT3 complex) (CD37) CD3-zeta (clone pBS NK1) 1 X55510 CD4 (low match) 1 S68043 CD4 antigen (p55) (CD4) 4 M12807 ------CD44 antigen (homing 6 XS6794 W -- -- function and Indian blood group system (CD44) CD48 antigen (B-cell 3 XO 6341 ------membrane protein) (CD48) CD53 antigen (CD53) 10 L11670 ------CD53 antigen (CD53) (low 1 M60871 match) CD63 antigen (melanoma 1 3 M59907 antigen) (CD63) CD68 antigen (CD68) 2 S57235 ------CD74 antigen (invariant 72 KO1144 ------+ high in many libraries polypeptide of major histocompatibility complex, class II antigen-associated) (CD74) CD79A antigen 2 M80462 -- (immunoglobulin-associated alpha) (CD79A) CD79B antigen 2 M89957 -- (immunoglobulin-associated beta) (CD79B) CD8 antigen, alpha 2 M27161 ------polypeptide (p32) (CD8A) CD8 antigen, beta polypeptide 1 X13445 W 1 (p37) (CD8B1) CD81 antigen (target of 1 M3368O ------antiproliferative antibody 1 (CD81) CD83 antigen (activated B 1 Q01151 B ------lymphocytes, mmunoglobulin Superfamily) (CD83) US 2011/0003295 A1 Jan. 6, 2011 17
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
CD84 antigen (leukocyte U82988 ------antigen) (CD84) CD86 antigen L25259 -- CD9 antigen (p24) (CD9) 2 M38690 ------CD97 antigen (CD97) 12 X847OO ------CD97 antigen (CD97) (noin- P48960 exact 59%) CD97 antigen (CD97) (non- X946.30 ------exact 62%) CDC23 (cell division cycle AFO53977 ------23, yeast, homolog) (CDC23) CDC37 homolog U63131 B ------Cdc42 effector protein 3 2 AF104857 B ------(CEP3) CDC-like kinase (CLK) L292.19 ------CDC-like kinase 2 (CLK2) AFO23268 B -- -- CDW52 antigen (CAMPATH- 13 X151.83 Tactivated ------1 antigen) (CDW52) cell cycle progression AFO11794 restoration 8 protein(CPR8) cell division cycle 10 4 S72008 ------(homologous to CDC10 of S. cerevisiae) (CDC10) cell division cycle 20, UOS340 ------S. cerevisiae homolog (CDC20) cell division cycle 25B 6 Z68092 ------(CDC25B) cell division cycle 2-like 1 1 AFO67514 (PITSLRE proteins) (CDC2L1) (non-exact 42%) cell division cycle 42 (GTP- 5 M35543 ------binding protein, 25 kD) (CDC42) cell division protein (non- 1 AFO 6301S exact 68%) CELL-CYCLE NUCLEAR 1 Q13033 AUTOANTIGENSG2NA (S/G2 NUCLEARANTIGEN) centromere protein B (80 kD) 1 X55039 -- -- (CENPB) cep250 centroSome associated 3 AFO226SS B -- -- protein ceroid-lipofuscinosis, 7 AFO17456 ------+ high in bone neuronal 2, late infantile (Jansky-Bielschowsky disease) (CLN2) c-fgr (=M63877 nonreceptor 6 XS22O6 protein-tyrosine kinase (fgr)) CGI-19 protein 3 AF132953.1 chaperonin containing TCP1, 1 X748O1 ------subunit 3 (gamma) (CCT3) chaperonin containing TCP1, 1 AFO26291 ------subunit 4 (delta) (CCT4) chaperonin containing TCP1, 4 L277O6 B -- -- subunit 6A (Zeta 1) (CCT6A) chaperonin containing TCP1, 4 AFO26292 B -- -- subunit 7 (eta) (CCTT) Chediak-Higashi syndrome 1 1 U67615 B, T ------(CHS1) lymphoma Chediak-Higashi syndrome 1 1 U67615 (CHS1) (low score) chemokine (C-C motif) 4 UO390S receptor 2 (CCR2) chemokine (C-C motif) 1 X85740 receptor 4 (CCR4) (low match) (may contain repeat) US 2011/0003295 A1 Jan. 6, 2011 18
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu chemokine (C-C motif) 6 L31581 receptor 7 (CCR7) chemokine (C-X3-C) receptor 5 U2O350 -- 1 (CX3CR1) chemokine (C X-C motif), S M99293 ------receptor 4 (fusin) (CXCR4) chitinase 3-like 1 (cartilage 2 M80927 ------glycoprotein-39) (CHI3L1) chitinase 3-like 2 (CHI3L2) 2 U498.35 ------chloride channel 1, skeletal 1 G1828O muscle (CLCN1) chloride channel 6 (CLCN6) 1 D28475 -- -- Chloride intracellular channel 1 U932OS ------1 (CLIC1) chondroitin sulfate 5 X15998 -- proteoglycan 2 (versican) (CSPG2) chondroitin sulfate 2 JO2814 -- -- proteoglycan core protein chromatin assembly factor 1 1 Q09028 p48 subunit (CAF-1 P4.8 Subunit) (retinoblastoma binding protein p48) (retinoblastoma-binding protein 4) (MSI1 protein homolog) chromodomain helicase DNA 2 AFOO6513 binding protein 1 (CHD1) chromodomain helicase DNA AFOS4177 binding protein 1-like (CHD1L) chromodomain helicase DNA AFOO6514 B ------binding protein 2 (CHD2) chromodomain helicase DNA AFOO6515 binding protein 3 (CHD3) chromodomain helicase DNA S X86691 ------binding protein 4 (CHD4) chromosome 1 open reading AFOS4176 rame 7 (C1 ORF7) chromosome 1 specific ABOO7962 transcript KIAAO493 chromosome 17 open reading AJOO8112 T -- rame 1B (C17ORF1B) chromosome 4 open reading AFOO6621 ------rame 1 (C4ORF1) chromosome condensation 1- 2 AFO6O2.19 ------ike (CHC1L) chromosome X open reading Y15164. B ------rame 5 (CXORF5) chromosome-associated 2 AFO92S64 B ------polypeptide C(CAP-C) ciga-2 AFO26944 cig5 3 AFO26941 citrate synthase (CS) 2 AFO47042 B ------class I major 2 U31372 histocompatibility antigen (HLA-Cw3) class I major 1 U31372 histocompatibility antigen (HLA-Cw3) (low match) clathrin assembly protein 3 U45976 B ------ymphoid myeloid leukemia (CALM) clathrin heavy chain 1 X55878 clathrin, heavy polypeptide- 1 D21260 ike 2 (CLTCL2) clathrin, light polypeptide 1 M2O472 (Lca) (CLTA) (low match) US 2011/0003295 A1 Jan. 6, 2011 19
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu clathrin- 3 D63475 ------associated assembly adaptor rotein, medium 1 (CLAPM1) cleavage stimulation factor, 3 1 M85085 pre-RNA, subunit 2 64 kD (CSTF2) (non-exact 82%) cleavage stimulation factor, 3 1 U15782 B ------pre-RNA, subunit 3, 77kD (CSTF3) ck3 1 L2922O B -- -- clone 23815 (Hs.82845) 1 U90916 ------clone 24592 mRNA sequence 1 D88378 ------Cld/MBL/SPA receptor 1 U94333 ClaR(p) () clusterin (complement lysis 1 M64722 ------inhibitor, SP-40.40, sulfated glycoprotein 2, testosterone repressed prostate message 2, apolipoprotein J) (CLU) CMP-sialic acid transporter 1 D87969 B -- -- (CMPST) CMRF35 3 X66171 c-myc Oncogene containing 1 XS4629 coxIII coagulation factor II 1 M62424 ------(thrombin) receptor (F2R) coagulation factor V 1 M1433S ------(proaccelerin, labile factor) (F5) coagulation factor XIIIa 3 M21998 Subunit coagulation factor XIII, A1 6 M143S4 ------polypeptide (F13A1) coated vesicle membrane 1 X92098 ------protein (RNP24) coatomer protein complex, S U241 OS T -- -- subunit alpha (COPA) Cofilin 1 (non-muscle) 13 X954.04 ------+ high in fetal brain (CFL1) cold inducible RNA-binding 7 D78134 ------protein (CIRBP) cold shock domain protein A 3 X953.25 -- -- (CSDA) collagen, type IX, alpha 2 3 AFO194O6 B (COL9A2) colony stimulating factor 1 3 XO3663 ------receptor, formerly McDonough feline sarcoma viral (v-films) oncogene homolog (CSF1R) colony stimulating factor 2 S MS9941 receptor, beta, low-affinity (granulocyte-macrophage) (CSF2RB) colony stimulating factor 2 1 MS9941 receptor, beta, low-affinity (granulocyte-macrophage) (CSF2RB) (low match) colony stimulating factor 3 16 X55720 -- receptor (granulocyte) complement component 5 1 M62SOS L receptor 1 (C5a ligand) (C5R1) conserved gene amplified in 2 AFOOO152 ------osteosarcoma (OS4) US 2011/0003295 A1 Jan. 6, 2011 20
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
COP9 (constitutive 2 AFO31647 ------photomorphogenic, Arabidopsis, homolog) subunit 3 (COPS3) COP9 homolog (HCOP9) 2 US 1205 B ------COPII protein, homolog of S. cerevisiae 4 X97O64 -- -- SEC23p (SEC23A) copine I (CPNE1) 2 U83246 B ------copine I (CPNE1) (low score) U83246 coproporphyrinogen oxidase D16611 ------(coproporphyria, harderoporphyria) (CPO) core-binding factor, beta L2O298 -- subunit (CBFB) coronin 22 X89109 T, W ------coronin (low match) U34690 coronin (non-exact, 71%) X89109 cot (cancer Osaka thyroid) D14497 ------oncogene (COT) cryptochrome 1 (photolyase- D84657 ------like) (CRY1) CTD (carboxy-terminal AFO81287 ------domain, RNA polymerase II, polypeptideA) phosphatase, subunit 1 (CTDP1) C-terminal binding protein 1 U37408 B ------(CTBP1) C-terminal binding protein 2 2 AFO16SO7 ------(CTBP2) CUG triplet repeat, RNA- 3 U63.289 ------binding protein 1 (CUGBP1) cullin 1 (CUL1) 3 US 8087 ------cullin 3 (CUL3) 2 US8O89 ------cut (Drosophila)-like 1 1 M74099 B -- (CCAAT displacement protein) (CUTL1) cyclin D2 (CCND2) 2 D13639 ------cyclin D3 (CCND3) 5 M92287 B, T -- -- lymphoma cyclin G1 (CNNG1) 1 D78341 B ------cyclin I 3 DSO310 B -- -- cyclin T2 (CNNT2) 1 AFO48732 B, T B lymphoma cyclin-dependent kinase 2 1 X62O71 (CDK2) cyclin-dependent kinase 1 S76986 inhibitor (p27Kip1) cyclin-dependent kinase 2 S67388 ------inhibitor 1A (p21, Cip1) (CDKN1A) CYP2D7-CYP2D6 intergenic 1 X90926 region (partial) cystatin B (stefin B) (CSTB) 1 LO3SS8 ------cysteine and glycine-rich 5 L54.057 -- protein 3 (cardiac LIM protein) (CSRP3) cytidine deaminase (CDA) 2 L27943 -- cytochrome b 1 AFO42SOO cytochrome b (CYTB) (isolate 1 AFO425.18 Aus5) cytochrome b(-245) beta chain 2 XO5895 N-terminal region (X-linked granulomatous disease gene) cytochrome b-245, beta 2 XO4011 ------polypeptide (chronic granulomatous disease) (CYBB) US 2011/0003295 A1 Jan. 6, 2011 21
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu cytochrome C 1 POOOO1 cytochrome c oxidase subunit 1 U90915 T ------IV (COX4) cytochrome c oxidase subunit 2 M592SO -- Vb (COX5B) cytochrome c oxidase subunit 6 ABOO7618 ------VII-related protein (COX7RP) cytokine Suppressive anti- L35263 lymphocyte ------inflammatory drug binding protein 1 (p38 MAP kinase) (CSBP1) Cytoplasmic S69272 -- antiproteinase = 38 kda intracellular serine proteinase inhibitor cytotoxic granule-associated S7.0114 RNA-binding protein p40 TIA-1 D123 (D123) D14878 ------D2-2 AFO 19226 damage-specific DNA binding 2 AJOO295S ------protein 1 (127 kD) (DDB1) DCHT (low match) AFO1763S DEAD H (Asp-Glu-Ala- U78524 ------Aspi His) box binding protein (DDXBP1) (Asp-Glu-Ala- 2 U59321 T ------box polypeptide s ( 7 2) i.AD/H (Asp-Glu-Ala- 1 X7O649 ------p/His) box polypeptide 1 DEAD H (Asp-Glu-Ala- 2 ABOO1636 Asp/His) box polypeptide 15
DEAD H (Asp-Glu-Ala- 2 ABO11149 ------Asp/His) box polypeptide 16
DEAD H (Asp-Glu-Ala- 3 USO553 ------Asp/His) box polypeptide 3
DEAD H (Asp-Glu-Ala- 37 X15729 ------Asp/His) box polypeptide 5 (RNA helicase, 68 kD) DEAD H (Asp-Glu-Ala- 1 AFO15812 Asp/His) box polypeptide 5 (RNA helicase, 68 kD) (DDX5) (low match) DEAD H (Asp-Glu-Ala- 2 D17532 -- -- Asp/His) box polypeptide 6 (RNA helicase, 54 kD)
DEAD H (Asp-Glu-Ala- 1 DSO487 ------Asp/His) box polypeptide 8 RNA helicase, 54 kD)
DEAD H (Asp-Glu-Ala- 3 L13848 ------Asp/His) box polypeptide 9 (RNA helicase A, nuclear DNA helicase II; leukophysin) (DDX9) DEAD H (Asp-Glu-Ala- 1 AFOOO985 ------Asp/His) box polypeptide, Y chromosome (DBY) US 2011/0003295 A1 Jan. 6, 2011 22
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Death associated protein 3 2 X83544 ------(DAP3) death effector domain- 1 AFO83236 ------containing protein (DEDD) death-associated protein 6 2 AFO39136 ------(DAXX) dedicator of cyto-kinesis 2 4 D86964 ------(DOCK2) defender against cell death 1 1 D15057 ------(DAD1) Defensin, alpha 1, myeloid- 4 L12690 ------related sequence (DEFA1) DEK gene (D6S231E) 1 X64229 B -- -- elta sleep inducing peptide, 4 ZSO781 ------immunoreactor (DSIPI) endritic cell protein (GA17) 3 AFO 64603 ------eoxycytidine kinase (DCK) 1 M60527 eoxyribonuclease II, 3 ABOO4574 lysosomal (DNASE2) DGS-I 2 L77566 -- iacylglycerol kinase 3 D16440 iacylglycerol kinase alpha 3 AFO64771 -- (DAGK1) (clone 24) iacylglycerol kinase alpha AFO64771 (DAGK1) (clone 24) (low match) iaphanous (Drosophila, AFOS1782 B, monocyte ------homolog) 1 (DIAPH1) stimulated iaphorase (NADH) YO95O1 ------(cytochrome b-5 reductase) (DIA1) ifferentiated Embryo ABOO4O66 ------Chondrocyte expressed gene 1 (DEC1) ifferentiated Embryo ABOO4O66 Chondrocyte expressed gene 1 (DEC1) (low match) ifferentiation antigen CD20 L2341S DiGeorge syndrome critical X84O76 ------region gene 2 (DGCR2) ihydrolipoamide 2 JO362O ------ehydrogenase (E3 component of pyruvate ehydrogenase complex, 2 OXO-glutarate complex, branched chain keto acid ehydrogenase complex) (DLD) ihydrolipoamide S- 1 YOO978 B -- -- acetyltransferase (E2 component of pyruvate ehydrogenase complex) (DLAT) ihydropyrimidinase-like 2 1 D78O13 ------(DPYSL2) inG gene 1 Y10571 iptheria toxin resistance 3 AFOS3003 B ------protein required for iphthamide biosynthesis (Saccharomyces)-like 2 (DPH2L2) isintegrin-protease (non- 1 Y13323 exact 72%) DJ-1 protein 2 AF021819 ------Dmx-like 1 (DMXL1) 1 AJOOS821 ------DNA (cytosine-5-)- 3 X63692 Tactivated, ------methyltransferase 1 (DNMT1) lymphoma DNA fragmentation factor, 40 kD, 1 AFO 64019 beta subunit (DFFB) US 2011/0003295 A1 Jan. 6, 2011 23
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
DNA fragmentation factor, 45 kD, 2 U91985 -- -- alpha subunit (DFFA) DNA mismatch repair protein 1 U17840 (hMLH1) DNA segment on M64241 ------high in many libraries chromosome X (unique) 648 expressed sequence DNA segment, single copy M73547 -- probe LNS-CAILNS-CAII (deleted in polyposis (DSS346) DNA-damage-inducible L24498 transcript 1 (DDIT1) (low match) DnaJ protein AJOO1309 DnaJ protein AJOO1309 ocking protein 2, 56 kD AFO34970 (DOK2) olichyl D89060 ------activated T cell iphosphooligosaccharide protein glycosyltransferase (DDOST) olichyl-phosphate D861.98 Tactivated -- mannosyltransferase polypeptide 1, catalytic subunit (DPM1) own-regulated by activation AJ2231.83 -- immunoglobulin Superfamily) DORA) own-regulated in adenoma DRA (low match) D-type cyclin-interacting -- protein 1 (DIP1) ual specificity phosphatase 1 X68277 -- -- (DUSP1) ual specificity phosphatase AFO23917 -- 11 (RNA/RNP complex 1 interacting) (dusp11) ual specificity phosphatase 3 LOS147 -- (vaccinia virus phosphatase VH1-related) (DUSP3) ual specificity phosphatase 6 X939.20 -- -- (DUSP6) ynactin 1 (p150, Glued Drosophila) homolog) DYTN1) ynactin 1 (p150, Glued Drosophila) homolog) DYTN1) (low match) ynamin 2 (DNM2) L36983 ynamitin (dynactin complex USO733 50 kD subunit) (DCTN-50) non-exact 88%) ynein, axonemal, heavy X99947 polypeptide 17-like (non exact, 57% aa) ynein, cytoplasmic, light AFO35812 intermediate polypeptide 2 DNCLI2) ynein, cytoplasmic, light AFO35812 intermediate polypeptide 2 DNCLI2) (non-exact, 69%) yskeratosis congenita 1, U591.51 -- yskerin (DKC1) ystonia 1, torsion (autosomal AFOOf871 -- ominant) (DYT1) ystrobrevin, beta (DTNB) AFO22728 US 2011/0003295 A1 Jan. 6, 2011 24
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu dystrophia myotonica- L19267 ------containing WD repeat motif (DMWD) dystrophia myotonica-protein LO883S ------kinase (DMPK) dystrophin (muscular X14298 dystrophy, Duchenne and Becker types) (DMD) (low match, 59% aa) E1B-55 kDa-associated protein AJOO7SO9 W ------E2F transcription factor 3 2 D385.50 ------(E2F3) E2F transcription factor 4, X86096 B -- -- p107p130-binding (E2F4) E2F transcription factor 5, 2 U15642 ------p130-binding (E2F5) E74-like factor 1 (ets domain M82882 B ------transcription factor) (ELF1) E74-like factor 4 (ets domain 3 U32645 ------transcription factor) (ELF4) E74-like factor 4 (ets domain U32645 transcription factor) (ELF4) (non-exact, 71%) early development regulator 2 4 U89278 ------(homolog of polyhomeotic 2) (EDR2) EBV induced G-protein 1 LO8.177 W coupled receptor (EBI2) ecotropic viral integration site 3 M60830 -- -- 2B (EVI2B) ectin, galactoside-binding, 1 O4456 -- Soluble, 1 (galectin 1) (LGALS1) EGF-like-domain, multiple 4 1 ABO11541 (EGFL4) elF-2-associated pé7 homolog 3 U13261 B -- -- elastin (Supravalvular aortic 1 M24782 -- -- stenosis, Williams-Beuren syndrome) (ELN) (low match) elav-type RNA-binding 3 U69S46 protein (ETR-3) electron-transfer-flavoprotein, 2 JO4058 -- alpha polypeptide (glutaric aciduria II) (ETFA) ELK3, ETS-domain protein 2 Z36715 -- -- (SRF accessory protein 2) (ELK3) elongation factor 1-beta L264.04 elongation factor Ts AF110399 (mitochondrial protein) elongation factor Tu-nuclear X84694 encoded mitochondrial eMDC II protein AJ242O15.1 ems1 sequence (mammary M983.43 ------tumor and squamous cell carcinoma-associated (p80/85 Src substrate) (EMS1) endogenous retroviral element Z70664 endosulfine alpha (ENSA) X999.06 T -- endothelial differentiation, 2 M31210 ------sphingolipid G-protein coupled receptor, 1 (EDG1) endothelial differentiation, M31210 sphingolipid G-protein coupled receptor, 1 (EDG1) (low match 66%) US 2011/0003295 A1 Jan. 6, 2011 25
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu endothelial monocyte- 1 U101.17 ------activating polypeptide (EMAPII) enolase 1, (alpha) (ENO1) 12 M14328 ------enolase 2, (gamma, neuronal) 1 XS1956 : (ENO2) enolase-alpha 1 D28437 enoyl Coenzyme A hydratase 2 U16660 , peroxisomal (ECH1) enoyl Coenzyme A hydratase, 1 D13900 ------short chain, 1, mitochondrial (ECHS1) ENOYL-COA HYDRATASE, 1 P3OO84 MITOCHONDRIAL PRECURSOR (SHORT CHAIN ENOYL-COA HYDRATASE) (SCEH) (ENOYL-COA HYDRATASE 1) (low match, non-exact 56%) epidermal growth factor 2 UO7707 ------receptor pathway substrate 15 (EPS15) EPIDIDYMAL SECRETORY 2 Q15668 PROTEINE1 PRECURSOR (EPI-1) (HE1) (EPIDIDYMAL SECRETORY PROTEIN 4.6) (ESP14.6) epithelial membrane protein 3 U87947 ------(EMP3) Epoxide hydrolase 1, L29766 -- microsomal (xenobiotic) only (EPHX1) ERCC2 (=LA7234) XS2221 ERF-2 3 UO78O2 ------+ high in gallbladder ERp28 protein X94910 ------erythrocyte membrane protein 2 M81 635 erythroleukemic cells K562 2 L25343 EST (Hs. 1895.09) 2 U24166 estrogen receptor-related L38487 protein (hERRal) ESTs, Highly similar to X66SO3 B, T -- -- ADENYLOSUCCINATE SYNTHETASE ESTs, Moderately similar to U28811 ------cysteine-rich fibroblast growth actor receptor ET binding factor 1 (SBF1) U931.81 -- ets domain protein ERF U15655 : -- -- : e ukaryotic translation 326 XO3SS8 f ------ongation factor 1 alpha 1 EEF1A1) karyotic translation XO3558 ongation factor 1 alpha 1 EEF1A1) (low match) karyotic translation XO3558 ongation factor 1 alpha 1 EEF1A1) (low match) ll karyotic translation S X60489 ------ongation factor 1 beta 2 EEF1B2) ukaryotic translation 1 Z21507 ------r 1 delta s E. ht EE. le ide exchange S ion 31 Z11S31 E.9. 8. i E.O r gamma US 2011/0003295 A1 Jan. 6, 2011 26
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu eukaryotic translation 2 XS1466 -- -- elongation factor 2 (EEF2) eukaryotic translation 1 JO2645 initiation factor 2, Subunit 1 (alpha, 35 kD) (EIF2S1) eukaryotic translation 1 M29536 initiation factor 2, Subunit 2 (beta, 38 kD) (EIF2S2) eukaryotic translation 3 L1916.1 -- -- initiation factor 2, subunit 3 (gamma, 52 kD) (EIF2S3) eukaryotic translation 2 U78311 initiation factor 3, subunit 10 (theta, 150/170 kD) (EIF3S10) eukaryotic translation 3 U36764 ------+ high in white blood initiation factor 3, subunit 2 cells (beta, 36 kD) (EIF3S2) eukaryotic translation 6 US4559 ------+ high in spleen initiation factor 3, subunit 3 (gamma, 40 kD) (EIF3S3) eukaryotic ion 9 AFO2O833 ------initiation fa subunit 4 (delta, 44 k ; F3S4) eukaryotic translation 4 U941.75 ------+ high in bladder initiation faC O r 3 subunit 6 (48 kD) (E eukaryotic Rs . ion 1 U62962 ------+ Highly represented initiation faC O r 3 subunit 6 (1.4833 pct) in library (EIF3S6) 36 human gall bladder eukaryotic translation 3 U54558 ------initiation factor 3, subunit 7 (Zeta, 66/67 kD) (EIF3S7) eukaryotic translation S U46O2S ------+ high in testis initiation factor 3, subunit 8, 110 KD (EIF3S8) eukaryotic translation 1 AFO12088 8. or 4 gamma, 1
slation 1 AFO12088 iation factor 4 gamma, 1 w match) karyotic translation 2 D12686 & f 8. ctor 4 gamma, 1 ic translation 6 U73824 ------N iation factor 4 gamma, 2 F4G2) karyotic translation 2 U76111 ------iation factor 4 gamma, 2 ( E FG2) ic translation 29 D13748 iation factor 4A, isoform 1 E A. ) ic translation 11 D306SS ------iation factor 4A, isoform 2 ( E F4A2) eukaryotic translation 18 X55733 ------initiation factor 4B (EIF4B) eukaryotic translation 1 PO6730 initiation factor 4E (EIF4E) Eukaryotic translation 3 L360S6 T, B ------initiation factor 4E binding protein 2 (EIF4EBP2) eukaryotic translation 2 Q15056 initiation factor 4H (EIF4H) eukaryotic translation 2 U494.36 ------initiation factor 5 (EIF5) US 2011/0003295 A1 Jan. 6, 2011 27
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu eukaryotic translation 2 U901.76 ------termination factor 1 (ETF1) EV12 protein 1 MSS.266 -- Ewing sarcoma breakpoint 1 X66899 ------region 1 (EWSR1) EWS/FLI1 activated transcript 2 AFO2O264 2 homolog (EAT-2) EWS-E1A-F chimeric protein 1 U3S622 excision repair cross- 1 M286SO ------complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence) (ERCC1) excision repair cross- 1 X699.78 ------complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome)) (ERCC5) exostoses (multiple)-like 3 1 AFOO1690 ------(EXTL3) F11 1 X77744 -- F1-ATPase beta subunit (F-1 2 XO3559 beta) Fanconianaemia group A 2 Z8309S Fanconi anemia, 1 X99226 ------complementation group A (FANCA) far upstream element (FUSE) 2 UOSO40 ------binding protein 1 (FUBP1) farnesyl diphosphate synthase 1 JOS262 ------(farnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase) (FDPS) airnesyl-diphosphate 2 X69141 ------arnesyltransferase 1 (FDFT1) arnesyltransferase, CAAX 2 LOO63S -- -- box, beta (FNTB) Fasligand (gene and promoter 1 AFO44583 region) Fas-ligand associated factor 1 1 UTO667 atty-acid-Coenzyme Aligase, 4 D10040 ------ong-chain 1 (FACL1) Fc fragment of IgA, receptor 1 XS41SO or (FCAR) Fc fragment of IgE, high 1 M331.9S ------affinity I, receptor for; gamma polypeptide (FCER1G) Fc fragment of IgE, low 2 XO4772 -- -- affinity II, receptor for (CD23A) (FCER2) Fc fragment of IgG, low 6 M31932 ------affinity IIa, receptor for (CD32) Fc fragment of IgG, low 1 X62572 ------affinity IIa, receptor for (CD32) (FCGR2A) Fc fragment of IgG, low 34 XO7934 ------affinity IIIa, receptor for (CD16) (FCGR3A) Fc fragment of IgG, receptor, 3 U12255 ------+ high in many libraries transporter, alpha (FCGRT) c-Igr 1 Z13983 Fc-gamma-receptorIIIB 2 M90746 US 2011/0003295 A1 Jan. 6, 2011 28
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu eline sarcoma (Snyder 3 XO6292 Theilen) viral (v-fes)/Fujinamiavian sarcoma (PRCII) viral (v-fps) oncogene homolog(FES) c-fes?fps) emale sterile homeotic 2 X96670 related gene 1 (mouse homolog) (FSRG1) erritin L-chain 9 YO9188 erritin, heavy polypeptide 1 4 M11146 (FTH1) ertilin alpha pseudogene 1 YO9232 etal Alzheimer antigen 2 UO5237 (FALZ) etal Ig heavy chain variable 1 M34024 region fibrillarin (FBL) 1 X56597 fibrinogen-like protein 2 3 Z36531 : (T49) fibroblast growth factor 1 M35718 receptor 2 (bacteria-expressed kinase, keratinocyte growth actor receptor, craniofacial dysostosis 1, Crouzon syndrome) syndrome, Pfeiffer syndrome, Jackson-Weiss) (FGFR2) icolin (collagen fibrinogen 19 D8392O domain-containing) 1 (FCN1) filaminA, alpha (actin 2 XS3416 binding protein-280) (FLNA) filamin B, beta (actin-binding 1 AFO43O45 protein-278) (FLNB) Finkel-Biskis-Reilly murine 2 X65923 -- Highly represented in sarcoma virus (FBR-MuSV) intraepithelial ubiquitously expressed (fox neoplasia and invasive derived); ribosomal protein prostate tumor S30 (FAU) K-506 binding protein 1 M8O199 -- K506-binding protein 1A 2 M34539 ( 12 kD) (FKBP1A) FK506-binding protein 1B 1 M92423 (12.6 kD) (FKBP1B) FK506-binding protein 5 4 U71321 FKBP5) Flightless I (Drosophila) 3 U80184 homolog (FLII) Flightless I (Drosophila) 1 U80184 homolog (FLII) (low match) FLN29 (FLN29) 2 ABOOf447 lotillin 2 (FLOT2) S M60922 -- olate receptor 2 (fetal) 1 AFOOO380 : (FOLR2) orkhead (Drosophila) 1 AFO32886 -- homolog (rhabdomyosarcoma) ike 1 (FKHRL1) Formyl peptide receptor 1 9 M60627 (FPR1) ormyl peptide receptor-like 1 1 M84562 Found only in libraries (FPRL1) from placenta ormyl peptide receptor-like 1 1 M84562 (FPRL1) (low score) ragile X mental retardation 1 1 L29074 (FMR1) ragile X mental retardation, 1 U251.65 autosomal homolog 1 (FXR1) Friend leukemia virus 3 M93255 integration 1 (FLI1) US 2011/0003295 A1 Jan. 6, 2011 29
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu fructose-bisphosphatase 1 D26054 -- -- (FBP1) FSHD-associated repeat U85056 DNA, proximal region fucose-1-phosphate AFO17445 ------guanylyltransferase (FPGT) full length insert cDNA clone AFO86122 ZA78A09 full length insert cDNA AFO7SO61 YPO7G10 fumarate hydratase (FH) U59309 ------FUS (low match) X99006 FYN-binding protein (FYB- 16 U93O49 -- -- 120/130) (FYB) Galpha interacting protein X91809 (GAIP) (low score) G protein beta subunit-like 2 D28398 protein 12.3 G protein-coupled receptor 64 X81892 -- (HE6) (non-exact 59%) G protein-coupled receptor 2 L16862 ------kinase 6 (GPRK6) G1 to S phase transition 1 2 X17644 ------(GSPT1) GA-binding protein 1 D13316 ------transcription factor, beta subunit 2 (47 kD) (GABPB2) galactose-1-phosphate 2 M60091 uridylyltransferase (GALT) galactosidase, beta 1 (GLB1) 3 M27508 ------galactosyltransferase 1 M13701 (=X13223 N acetylglucosamide-(beta 1-4)- galactosyltransferase) galectin-9 isoform 1 ABOO6782 ------gamma2-adaptin (G2AD) 1 AFO 687O6 ------gamma-actin 2 M371.30 gamma-aminobutyric acid 2 AJO121.87 ------(GABA) B receptor 1 (GABBR1) GATA-binding protein 2 1 M68891 -- -- (GATA2) GATA-binding protein 3 1 M69106 ------(GATA3) GCN5 (general control of 3 D64007 ------amino-acid synthesis, yeast, homolog)-like 1 (GCN5L1) GDP dissociation inhibitor 1 1 D4SO21 ------+ high in adult brain (GDI1) GDP dissociation inhibitor 2 4 Y13286 (GCI2) GDS-related protein 4 U68142 ------(HKE1.5) gelsolin (amyloidosis, Finnish 3 XO4412 ------type) (GSN) general transcription factor II, 4 Y14946 ------I (GTF2I) general transcription factor II, 1 AFO38968 ------+ high in fetal brain i, pseudogene 1 (GTF2IP1) general transcription factor 4 X64037 ------IIF, polypeptide 1 (74 kD subunit) (GTF2F1) general transcription factor 2 Z30093 B, T IIH, polypeptide 3 (34 kD subunit) (GTF2H3) general transcription factor 3 YO7595 ------IIH, polypeptide 4 (52 kD subunit) (GTF2H4) US 2011/0003295 A1 Jan. 6, 2011 30
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu general transcription factor 1 U14134 ------IIA (GTF3A) general transcription factor 1 UO2619 -- -- IIC, polypeptide 1 (alpha subunit, 220 kD) (GTF3C1) general transcription factor 3 D13636 ------IIC, polypeptide 2 (beta subunit, 110 kD) (GTF3C2) germline immunoglobulin LO6612 heavy chain (IGHV (a)) germline immunoglobulin X92236 heavy chain, variabl region germline immunoglobulin X92343 heavy chain, variable region, (21-2) GLE1 (yeast homolog)-like, AFOS8922 -- -- RNA export mediator (GLE1L) glia maturation factor, beta ABOO1106 ------(GMFB) glioma-associated oncogene XO7384 homolog (Zinc finger protein) (GLI) 9. ioma-associated oncogene XO7384 homolog (zinc fingerprotein) (GLI) (low score) globin, alpha 2 WOOS16 glucocorticoid receptor M32284 (=M69104) glucocorticoid receptor (GRL) 2 U80947 ------glucos phosphate isomerase LO91OS (CONTAINS LARGE REPEAT) glucosamine (N-acetyl)-6- Z12173 -- Sulfatase (Sanfilippo disease IIID) (GNS) glucosamine (N-acetyl)-6- Z12173 Sulfatase (Sanfilippo disease IIID) (GNS) (non-exact 56%) glucose transporter-like M2O681 ------protein-III (GLUT3) glucose transporter-like M2O681 protein-III (GLUT3) (low match) glucosidase, alpha; acid YOO839 ------(Pompe disease, glycogen storage disease type II) (GAA) glucosidase, beta; acid KO2920 ------(includes glucosylceramidase) (GBA) glutamate dehydrogenase 1 M2O867 ------(GLUD1) glutamate-ammonia ligase 12 XS9834 ------(glutamine synthase) (GLUL) glutamate-ammonia ligase YOO387 (glutamine synthase) (GLUL) (low score) glutamate-cysteine ligase M90656 -- (gamma-glutamylcysteine synthetase), catalytic (72.8 kD) (GLCLC) glutamine cyclotransferase X71125 -- -- glutamine-fructose-6- M90516 -- -- phosphate transaminase 1 (GFPT1) glutaminyl-tRNA synthetase X72396 glutaminyl-tRNA synthetase 6 X76O13 ------(QARS) US 2011/0003295 A1 Jan. 6, 2011 31
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu glutamyl-prolyl-tRNA XS4326 synthetase (EPRS) glutathione peroxidase 1 2 M21304 ------(GPX1) glutathione peroxidase 4 X71973 ------(phospholipid hydroperoxidase) (GPX4) glutathione S-transferase pi U3O897 ------(GSTP1) glutathione S-transferase AF070657 Subunit 13 homolog glyceraldehyde-3-phosphate 12 JO2642 -- dehydrogenase (GAPD) glycogenin (GYG) U31525 ------glycophorin C (Gerbich blood X12496 ------group) (GYPC) glycoprotein M6B (GPM6B) U45955 -- -- glycyl-tRNA synthetase UO9587 ------(GARS) glyoxalase I (lactoyl LO7837 ------glutathione lyase) (GLYI) golgi autoantigen, golgin US 1587 -- -- Subfamily a, 1 (GOLGA1) golgi autoantigen, golgin LO6147 Subfamily a, 2 (GOLGA2) (non-exact, 70%) golgi autoantigen, golgin U31906 Subfamily a, 4 (GOLGA4) golgi autoantigen, golgin X75304 ------Subfamily b, macrogolgin (with transmembrane signal), 1 (GOLGB1) gp25L2 protein 4 X90872 grancalcin 8 M81637 ------granulin (GRN) 16 X62320 ------granulin (GRN) (low match) 1 X62320 Granulysin (NKG5) 5 M85276 -- -- granzyme A (granzyme 1, 1 M18737 ------cytotoxic T-lymphocyte associated serine esterase 3) (GZMA) GRB2-related adaptor protein 1 US 2518 T only (GRAP) Grb2-related adaptor protein 2 1 AF090456 T -- (GRAP2) GRO1 oncogene (melanoma 1 XS4489 -- -- growth stimulating activity, alpha) (GRO1) growth arrest and DNA- 1 S4O7O6 damage-inducible gene (GADD153) growth arrest-specific 7 4 ABOO7854 -- -- (GAS7) growth factor receptor-bound 1 X62852 B ------protein 2 (GRB2) GS1 (protein of unknown 1 M86934 ------function) GS3955 4 D87119 ------GTP binding protein 1 1 U87964 ------(GTPBP1) GTP binding protein similar 1 U87791 ------to S. cerevisiae HBS1 (HBS1) GTPase activating protein-like 1 ABO11110 ------+ high fetal brain (GAPL) GTP-binding protein (low 1 Z49068 match) US 2011/0003295 A1 Jan. 6, 2011 32
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu GTP-binding protein G(K), 1 PO8754 alpha subunit (=G(I)ALPHA 3)(=GTP-binding regulatory protein Gi alpha-3 chain) Gu protein (GURDB) 2 U41387 ------guanine nucleotide binding 1 protein guanine nucleotide binding 4 JO3OO4 ------protein (G protein), alpha inhibiting activity polypeptide 2 (GNAI2) guanine nucleotide binding 7 M20597 ------protein (G protein), alpha inhibiting activity polypeptide 3 (GNAI3) guanine nucleotide binding 2 XO4409 B, T ------protein (G protein), alpha stimulating activity polypeptide 1 (GNAS1) guanine nucleotide binding 1 Z18859 protein (G protein), alpha transducing activity polypeptide 2 (GNAT2) guanine nucleotide binding 2 AFO17656 ------protein (G protein), beta 5 (GNB5) guanine nucleotide binding S M36430 ------protein (G protein), beta polypeptide 1 (GNB1) guanine nucleotide binding 2 AFO11496 ------protein (G protein), q polypeptide (GNAQ) guanine nucleotide binding 1 L2566S ------protein-like 1 (GNL1) guanine nucleotide exchange 1 L13857 ------actor guanine nucleotide regulatory 1 X15610 ------actor (LFP40) guanine nucleotide regulatory 1 U72206 ------actor (LFP40) GUANINE NUCLEOTIDE- 1 P25388 BINDING PROTEINBETA SUBUNIT LIKE PROTEIN 2.3 (P205) (RECEPTOR OF ACTIVATED PROTEIN KINASEC 1) (RACK1) GUANINE- 1 U10860 -- MONOPHOSPHATE SYNTHETASE (GMPS) guanosine monophosphate 1 M24470 reductase (GMPR) (non-exact, 72%) guanosine-diphosphatase like 1 AFO16032 protein guanylate binding protein 1, 2 M55542 ------interferon-inducible, 67 kD (GBP1) guanylate binding protein 2, 6 MSSS43 ------interferon-inducible (GBP2) H2A histone family, member 1 Z83742
H2A histone family, member 2 AFO41483 ------Y (H2AY) H2B histone family, member 2 Z80783 ------+ high in adrenal gland L(H2BFL) tumor h2-calponin 1 D86059 H-2K binding factor-2 1 LO8904 ------H3 histone family, member K 1 Z83735 US 2011/0003295 A1 Jan. 6, 2011 33
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
3 histone, family 3A 7 M11353 ------high in ovary
3 histone, family 3B 15 Z4.8950 ------high in endothelial cells 1 U68494 ------S hock 27 kD protein 1 U12404 : ------P shock 40 kD protein 1 D85429 -- high in testis P S hock 60 kD protein 1 M22.382 -- ( C 8.p e O ill l ) ( H SPD1) shock 70 kD protein 1 MS9828 -- high in activated T cells shock 70 kD protein 5 13 X87949 cose-regulated protein, 8 kD) (HSPA5) eat shock 70 kD protein 6 X51757 -- eat shock 70 kD protein 9B L151.89 rtalin-2) (HSPA9B) EAT SHOCK COGNATE P11142 71 KD PROTEIN heat shock factor binding AFO 687 S4 protein 1 (HSBP1) heat shock protein 90 13 M27024 ------high in many libraries heat shock protein, DNAJ-like D13388 ------2 (HSJ2) Hect (homologous to the E6 USOO78 -- -- AP (UBE3A) carboxyl erminus) domain and RCC1 (CHC1)-like domain (RLD) 1 (HERC1) hect domain and RLD 2 ABOO2391 ------(HERC2) helicase-like protein (HLP) X98378 ------helix-loop-helix protein HE47 M65214 -- (E2A) hematopoietic cell-specific X16663 ------Lyn Substrate 1 (HCLS1) heme oxygenase (decycling) 1 XO6985 ------(HMOX1) HEMOGLOBINALPHA P19015 CHAIN hemoglobin beta (beta globin) AF117710 hemoglobin, alpha 1 (HBA1) 30 WOO491 ------hemoglobin, alpha 1 (HBA1) WOO491 (low match) hemoglobin, alpha 1 (low WOO493 match) hemoglobin, alpha 1 (non JOO153 exact, 76%) hemoglobin, alpha 1 (non WOO493 exact, 82%) hemoglobin, beta (HBB) 129 WOO497 -- high in many libraries hemoglobin, beta (HBB) (low WOO497 match) hemoglobin, beta (HBB) (low match) hemokine (C X—C motif), D10924 ------receptor 4 (fusin) (CXCR4) hemopoietic cell kinase M16591 -- -- (HCK) hepatitis C-associated D28908 microtubular aggregate protein p44 hepatoma-derived growth D16431 ------actor US 2011/0003295 A1 Jan. 6, 2011 34
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Hermansky-Pudlak syndrome 2 U65676 (HPS) HERV-E integrase (non-exact 1 AFO26246 76% aa) heterogeneous nuclear protein 2 S63912 -- similar to rathelix destabilizing protein (FBRNP) heterogeneous nuclear 4 M16342 ribonucleoprotein (C1/C2) (HNRPC) heterogeneous nuclear 1 M6SO28 -- -- ribonucleoprotein AB (HNRPAB) heterogeneous nuclear 2O X12671 -- -- High in alveolar ribonucleoprotein A1 rhabdomyosarcoma (HNRPA1) heterogeneous nuclear 3 M29064 -- -- High in activated T ribonucleoprotein A2B1 cell, fetal brain (HNRPA2B1) heterogeneous nuclear 2 D55673 -- -- ribonucleoprotein D (hnRNPD) heterogeneous nuclear S D89092 -- -- ribonucleoprotein D-like (HNRPDL) heterogeneous nuclear 1 L28O10 -- ribonucleoprotein F (HNRPF) heterogeneous nuclear 1 L28O10 ribonucleoprotein F (HNRPF) (83%) heterogeneous nuclear 2 Z23064 -- ribonucleoprotein G (HNRPG) heterogeneous nuclear 3 P55795 ribonucleoprotein H (HNRPH) (FTP-3) heterogeneous nuclear 1 P31943 ribonucleoprotein H (HNRPH) (low match) heterogeneous nuclear 2 L22009 -- ribonucleoprotein H1 (H) (HNRPH1) heterogeneous nuclear 21 S74678 -- -- ribonucleoprotein K (HNRPK) heterogeneous nuclear 1 AFOOO364 -- -- ribonucleoprotein R (HNRPR) heterogeneous nuclear 3 X65488 -- -- ribonucleoprotein U (scaffold attachment factor A) (HNRPU) hexokinase 1 (HK1) 2 X66957 -- hexokinase 2 (HK2) 3 Z46376 -- hexokinase 3 (HK3) 2 US 1333 hexosaminidase A (alpha 1 S62047 polypeptide) (HEXA HGMPO7I gene for olfactory 2 U76377 receptor High density lipoprotein 2 M64098 -- -- binding protein (HDLBP) high-mobility group 5 X12597 -- -- (nonhistone chromosomal) protein 1 (HMG1) high-mobility group 1 D63874 (nonhistone chromosomal) protein 1 (HMG1) (non-exact 60%) US 2011/0003295 A1 Jan. 6, 2011 35
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
High-mobility group 2 M12623 ------(nonhistone chromosomal) protein 17 (HMG17) high-mobility group 2 M8366S ------(nonhistone chromosomal) protein 2 (HMG2) high-mobility group 2 L17131 -- -- (nonhistone chromosomal) protein isoforms I and Y high-risk humanpapilloma 1 AFO90990.1 viruses E6 oncoproteins argeted protein E6TP1 beta (=AB007900 KIAAO440) histidine ammonia-lyase 1 D16626 (HAL) only istidyl-tRNA synthetase 2 Z11S18 ------HARS) istocompatibility antigen 1 U31372 LA-Cw3), class I istone deacetylase 1 (HDAC) U50079 -- istone deacetylase 1 s DSO4OS : : : -- : HDAC1) istone deacetylase 5 (NY AFO39691 O-9) K2 gene for hexokinase II Z46362 HL9 monocyte inhibitory 2 U91928 -- receptor precursor HLA class I heavy chain LA-Cw81701) HLA class I locus Cheavy X58536 chain HLA class II SB 4-beta chain HLA class III region -- containing NOTCH4 gene HLA-A Z72423 HLA-A 2 AJOO6O20 AJ223060 HLA-A11 UO2934 HLA-B 2 X75953 HLA-B X834O1 HLA-B X78426 HLA-Bassociated transcript-1 Z37166 ------D6S81E) LA-Bassociated transcript-2 2 M33509 -- -- D6S51E) LA-B81529 4 D445O1 HLA-BwT2 antigen 119 LO9736 ------high in many libraries HLA-C gene (HLA-Cw-0701 1 D83957 allele) HLA-Cw*O70 Z468.10 HLA-Cw*08O D641.51 HLA-Cw*1203 D64146 HLA-DC classII XOO370 histocompatibility antigens alpha-chain (=KO1160) HLA-DRalpha-chain M60333 ------high in spleen HLA-F (leukocyte antigen F) X17093 : -- -- HMG box containing protein 1 AFO 19214 hMLH1 (=U83845) ABO17806.1 Hmob33 Y14155 HMT1 (hnRNP U802.13 -- -- methyltransferase, S. cerevisiae)- ike 1 (HRMT1L1) nRNP C1, C2 2 D28382 homeobox (=X58250 Mouse homeo box protein, put. transcription factor involved in embryogenesis and hematopoiesis) US 2011/0003295 A1 Jan. 6, 2011 36
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br K Li Lu homeobox protein (HLX1) 1 U14326 (= M60721) homeodomain-interacting 1 AFOO4849 -- protein kinase 3 (HIPK3) homolog of Drosophia past 2 AFOO1434 -- (PAST) homolog of yeast (S. cerevisiae) 3 DSO916 ufd2 (UFD2) HPV 16 E1 protein binding U96131 protein HRIHFB2157 ABO15344 HRX-like protein YO8836 (=AFO10403 ALR) hsc70 gene for 71 kd heat 3 YOO371 shock cognate protein HSPCO)12 AFO77036.1 HSPCO21 AFO772O7.1 HsPex13p U71374 htra,2-beta-2 U87836 U60644 hunc18b2 U63533 HUNKI Y12059 : : : huntingtin-interacting protein AFO49528 HYPA/FBP11 (HYPA) hVps41p (HVPS41) U87309 hydroxyacyl-Coenzyme A UO4627 dehydrogenase 3-ketoacyl Coenzyme A thiolasetenoyl Coenzyme A hydratase (trifunctional protein), alpha subunit (HADHA) hydroxyacyl-Coenzyme A 1 D16481 dehydrogenase 3-ketoacyl Coenzyme A thiolasetenoyl Coenzyme A hydratase (trifunctional protein), beta subunit (HADHB) hydroxysteroid (17-beta) 1 U34879 dehydrogenase 1 (HSD17B1) hypothetical protein 1 hypothetical protein 1 (ALOO8729) (d.J257A7.2) hypothetical protein 1 U96629 (CIT987SK 2A8 1 chromosome 8) hypothetical protein (clone 1 AFOSSOO4 24640) hypothetical protein (clone 1 Z70222 CRFp507G2490). hypothetical protein 1 ALO22238 (d.J1042K10.4) (non-exact 76%) hypothetical protein 2 ALO31432 (d.J465N24.1 similar to predicted yeast and worm proteins) hypothetical protein 2 ALOO873O (d.J487J7.1.1) hypothetical protein 2 ALO23653 (d.J753P9.2) hypothetical protein 1 ALOSO1311 (DKFZp586I111) hypothetical protein 1 ALOO8729 (J257A7.2) hypothetical protein 1 ABOO7900 (KIAAO440) (=AF026504 R. norvegicus SPA-1 like protein) US 2011/0003295 A1 Jan. 6, 2011 37
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu hypothetical protein (L1H3' 1 region) hypothetical protein (S164) 1 P49756 hypothetical protein (similar 1 AF109907 o thrombospondin) (non exact 56%) hypothetical protein 3 1 hypothetical protein B 1 U47926 (HSU47926) (non-exact, 56%) hypothetical protein from 3 USO532 ------BCRA2 region (CG005) hypoxia-inducible factor 1, 1 AFOSO115 alpha subunit (basic helix oop-helix transcription actor) (HIF1A) a-associated invariant 1 M13555 gamma-chain (clones lambda y (1,2,3)) iduronate 2-sulfatase (Hunter 2 MS8342 ------syndrome) (IDS) g heavy chain V region L2O779 (=D11016) g heavy chain variable region 2 M34024 g heavy chain variable region Z75378 (VH4DJ) (clone T14.4) g heavy chain variable region Z75392 (VH4DJ) (clone T22.18) g J chain M12378 g Kappa S49007 G kappa light chain variable X63398 region A20 gkappa light chain, V- and J- D90158 region (=X59315) glambda light chain variable Z85052 region (26-34ITIIIF 120) g mu-chain VDJ4-region M16949 grearranged anti-myelin M29469 kappa-chain (V-J4-region, hybridoma AE6-5) grearranged H-chain mRNA 2 M9792O V-region grearranged light-chain V M74O2O region (=D90158) GF-II mRNA-binding protein U971.88 ------3 (KOC1) (non-exact, 75%) gGFc-binding protein D84239 ------(FC(GAMMA)BP) gG heavy chain variable M83136 region (vH26) gM heavy chain (C mu, X14939 membrane exons) kB kinase-beta (IKK-beta) AFO29684 L-1 receptor type II U14177 L2-inducible T-cell kinase 2 S6S186 (ITK) immediate early protein M62831 ------(ETR101) immunogloblin light chain D870 18 (lambda) Immunoglobulin (CD79A) YO8915 B, T ------binding protein 1 (IGBP1) immunoglobulin C (mu) and 2 X573.31 C (delta) heavy chain (=KO2878) immunoglobulin G Fc 1 Z46223 receptor IIIB US 2011/0003295 A1 Jan. 6, 2011 38
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu immunoglobulingamma 3 3 Y14.737 -- -- + high in many libraries (Gm marker) (IGHG3) immunoglobulingamma 1 Z66542 heavy chain variable region (=X61011) immunoglobulin heavy chain 1 X62109 (VI-3B) immunoglobulin heavy chain 1 X86356 J region immunoglobulin heavy chain 2 X86355 J region, B1 haplotype immunoglobulin heavy chain 1 AFO 62126 variable region (IGH) (clone 21u-48) immunoglobulin heavy chain 1 AFO 62212 variable region (IGH) (clone 23u-1) immunoglobulin heavy chain 2 M99641 variable region V1-18 GHV(a)) (=X60503) immunoglobulin heavy chain 2 M99672 variable region V3–43 (IGHV(a)) immunoglobulin heavy chain 3 M99649 variable region V3-7 (IGHV(a)) immunoglobulin IgEI heavy UO7986 chain Fc fragmen immunoglobulin kappa light XS8081 chain immunoglobulin kappa light X12686 chain V-segment A27 immunoglobulin light chain D86990 immunoglobulin light chain D86996 (low match) immunoglobulin light chain L29157 variable region (lambda IIIb Subgroup) from IgM rheumatoid factor immunoglobulin Mheavy S50735 chain V region = anti-lipid A antibody immunoglobulin mu (IGHM) 9 X57086 ------immunoglobulin mu binding L24544 T -- -- protein 2 (IGHMBP2) immunoglobulin Superfamily, Z33642 member 2 (IGSF2) Immunoglobulin VH mRNA X61013 (487 bp) (=M99652 immunoglobulin heavy chain variable region V3-11 (IGHV(a)) imogen 38 (IMOGEN38) 1 Z68747 ------IMP (inosine monophosphate) 1 JO5272 ------dehydrogenase 1 (IMPDH1) IMP (inosine monophosphate) 2 L39210 ------dehydrogenase 2 (IMPDH2) inc finger protein 151 (pHZ- 1 YO9723 ------67) (ZNF151) inc finger protein, C2H2, 1 AFO11573 -- -- rapidly turned over (ZNF20) inducible poly(A)-binding 1 U33818 ------protein (IPABP) inducible poly(A)-binding 1 U33818 protein (IPABP) (low match) inducible protein (HS.80313) 2 L47738 ------inhibitor of DNA binding 2, 4 M97796 ------dominant negative helix-loop helix protein (ID2) US 2011/0003295 A1 Jan. 6, 2011 39
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu inhibitor of kappa light 2 AFO44-195 polypeptide gene enhancer in B-cells, kinase complex associated protein (IKBKAP) inositol 1,3,4-trisphosphate US 1336 ------5.6-kinase inositol 14.5 trisphosphate U238SO ------receptor type 1 (ITPR1) inositol 1,4,5-trisphosphate 3- 2 X572O6 B ------kinase B (ITPKB) inositol monophosphatase S3898O inositol polyphosphate-5- 2 U84400 ------phosphatase, 145 kD (INPP5D) Ins(1,3,4,5)P4-binding protein X89399 -- -- insulin-like growth factor 2 5 YOO285 ------receptor (IGF2R) integral membrane protein 1 L38961 ------(ITM1) integral membrane protein 2C AFO3895.3 T ------(ITM2C) integral membrane protein 3 U61734 ------Tmp21-I (p23) integrin beta 4 binding protein 2 AFO47433 -- -- (ITGB4BP) integrin, alpha2b (platelet 3 M3448O -- -- glycoprotein IIb of IIb, IIIa complex, antigen CD41B) (ITGA2B) integrin, alpha 5 (fibronectin 4 XO6256 ------receptor, alpha polypeptide) (ITGA5) integrin, alpha L (antigen 6 YOO796 CD11A (p180), lymphocyte function-associated antigen 1: alpha polypeptide) (ITGAL) integrin, alpha M 1 M18044 (complement componentreceptor 3, alpha; also known as CD11b (p170), macrophage antigen alpha polypeptide) (ITGAM) integrin, alpha X (antigen 1 M81695 ------CD11C (p150), alpha polypeptide) (ITGAX) integrin, beta 1 (fibronectin 2 XO7979 receptor, beta polypeptide, antigen CD29 includes MDF2 MSK12) (ITGB1) integrin, beta 2 (antigen CD18 32 M15395 ------(p95), lymphocyte function associated antigen 1: macrophage antigen 1 (mac-1) beta subunit) (ITGB2) integrin, beta 7 (ITGB7) 1 M68892 -- Integrin-linked kinase (ILK) 1 U4O282 ------intercellular adhesion 1 JO3132 ------molecule 1 (CD54), human rhinovirus receptor (ICAM1) intercellular adhesion 1 X15606 ------molecule 2 (ICAM2) intercellular adhesion 6 X698.19 -- -- molecule 3 (ICAM3) intercellular adhesion 1 L27670 -- molecule 4, Landsteiner Wiener blood group (ICAM4) US 2011/0003295 A1 Jan. 6, 2011 40
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu Interferon consensus sequence 1 M91196 W, T binding protein 1 (ICSBP1) lymphoma Interferon consensus sequence 1 M91196 binding protein 1 (ICSBP1) (low match) interferon regulatory factor 2 4 X15949 ------(IRF2) interferon regulatory factor 1 4 LOSO72 ------(IRF1) interferon regulatory factor 5 1 US 1127 ------(IRF5) interferon, gamma-inducible 2 M63838 ------protein 16 (IFI16) interferon, gamma-inducible 9 JO3909 ------protein 30 (IFI30) INTERFERON-INDUCED 1 P32455 GUANYLATE-BINDING PROTEIN 1 (GUANINE NUCLEOTIDE-BINDING PROTEIN 1) (non-exact 62%) interferon-induced protein 17 3 X84958 ------(IFI17) interferon-induced protein 54 S. M14660 (IFI54) interferon-inducible (1-8D) 5 X57351 T ------interferon-inducible (1-8U) 1 X57352 ------interferon-related 5 Y10313 ------developmental regulator 1 (IFRD1) interferon-stimulated 2 M87503 ------transcription factor 3, gamma (48 kD) (ISGF3G) interleukin 1 receptor, type II 1 U64O94 -- (IL1R2) Interleukin 10 receptor, beta 1 UO8988 Tactivated -- -- (I.10RB) interleukin 12 receptor, beta 1 2 UO31.87 -- only found in T cell (IL12RB1) interleukin 13 receptor, alpha 2 YO9328 ------1 (IL13RA1) interleukin 16 (lymphocyte 6 U82972 -- chemoattractant factor) (IL16) interleukin 18 receptor 1 1 U43672 (IL18R1) interleukin 2 receptor, beta 9 M26062 (IL2RB) interleukin 2 receptor, gamma 6 D11086 ------(severe combined immunodeficiency) (IL2RG) interleukin 4 receptor (IL4R) 3 X5242S ------interleukin 6 receptor (IL6R) S X12830 -- -- interleukin 6 signal transducer 1 M57230 (gp130, oncostatin M receptor) (IL6ST) interleukin 7 receptor (IL7R) 14 M29696 -- -- interleukin 7 receptor (IL7R) 1 AFO43123 (low match) interleukin 8 (IL8) 8 YOO787 ------High in activated T cells, bone and pancreatic islets interleukin 8 receptor alpha 11 L19591 (IL8RA) interleukin 8 receptor, beta 14 M94582 (IL8RB) interleukin enhancer binding 3 U10323 ------+ high in uterus factor 2, 45 kD (ILF2) interleukin enhancer binding 2 U10324 factor 3,90 kD (ILF3) US 2011/0003295 A1 Jan. 6, 2011 41
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu interleukin-1 receptor- 2 L76.191 ------associated kinase 1 (IRAK1) interleukin-1 receptor- 1 US 2112 associated kinase 1 (low match) interleukin-10 receptor, alpha 5 UOO672 ------(IL1ORA) interleukin-11 receptor, alpha 7 Z38102 -- -- (IL11RA) INTERLEUKIN-14 1 P40222 PRECURSOR(IL-14) (HIGH MOLECULARWEIGHT B CELL GROWTH FACTOR) (HMW-BCGF) (non-exact 46%) intestinal carboxylesterase: 1 U60553 -- -- liver carboxylesterase-2 (ICE) inversin protein (non-exact 1 AFO84367 52%) IQ motif containing GTPase 6 L33075 activating protein 1 (IQGAP1) IQ motif containing GTPase 1 US 1903 -- -- activating protein 2 (IQGAP2) isocitrate dehydrogenase 1 1 AFO2OO38 ------(NADP+), soluble (IDH1) isocitrate dehydrogenase 2 2 X69433 ------(NADP+), mitochondrial (IDH2) isocitrate dehydrogenase 3 2 UO7681 -- (NAD+) alpha (IDH3A) isocitrate dehydrogenase 3 1 Z68907 ------(NAD+) gamma (IDH3G) isolate Aus3 cytochrome b 1 AFO42S16 (CYTB) isolate TZCCR5-179 CCR5 1 AFO11524 receptor (CCR5) isopentenyl-diphosphate delta 5 X17025 ------isomerase (IDI1) anus kinase 1 (a protein 4 M64174 ------tyrosine kinase) (JAK1) anus kinase 2 (a protein 1 AFOOS216 tyrosine kinase) (JAK2) k-recombination signal 2 LO7876 binding protein (RBPJK) M1 protein 1 AJOOS890 -- -- jumonji (mouse) homolog 1 US7592 ------(JMJ) jun D proto-oncogene (JUND) 1 XS1346 ------jun dimerization protein 1 AF111167 only found in germ junction plakoglobin (JUP) 1 M23410 ------kangai 1 (Suppression of 1 U20770 ------tumorigenicity 6, prostate; CD82 antigen (R2 leukocyte antigen, antigen detected by monoclonal and antibody A4)) (KAI1) karyopherin (importin) beta 1 2 L39793 ------(KPNB1) karyopherin (importin) beta 2 1 UT2395 ------(KPNB2) karyopherin alpha 1 (importin 1 S75295 ------alpha 5) (KPNA1) karyopherin alpha 2 (RAG 1 UO9559 cohort 1, importin alpha 1) (DPNA2) karyopherin alpha 3 (importin 1 D89618 -- -- alpha 4) (KPNA3)
US 2011/0003295 A1 Jan. 6, 2011 44
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
AAO379 BOO2377 -- AA0379 (non-exact, 65%) BOO2377 AA0380 (KIAA0380) BOO2378 -- -- AA0380 (KIAA0380) BOO2378 0% aa) AA0382 (KIAA0382) BOO238O AAO383 BOO2381 AA0386 (KIAA0386) BOO2384 AAO392 BOO2390 AA0397 (KIAA0397) BOO7857 AAO403 BOO7863 AAO404 BOO7864 AAO409 BOO7869 : AA0421 BOO7881 -- -- AA0424 (non-exact 82%) BOO7884 AA0428 (KIAA0428) 3829 AA0429 (KIAA0429) BOO7889 ------AA0430 (KIAA0430) BOO7890 only in ovary AA0432 (KIAA0432) 86753 -- AA0435 (KIAA0435) BOO7895 AA0438 (KIAA0438) BOO7898 ------AA0447 (KIAA0447) BOO7916 ------AAO449 BOO7918 -- AAO456 BOO7925 ------AA0458 (KIAA0458) BOO7927 AAO462 BOO7931 ------AAO465 BOO7934 ------AA0476 (KIAA0476) BOO7945 -- -- AAO489 BOO7958 AA0494 (KIAA0494) BOO7963 ------AAOS 15 BO O87 ------AAOS21 BO O93 -- AAOS25 BO 097 -- AAO530 BO O2 -- -- AAOS32 BO O4 ------AAO537 (KIAA0537) BO 09 AAOS40 BO 12 ------AAOS43 BO 15 ------AAOS44 BO 16 ------AAOS49 BO 21 ------AAOSS1 : BO 23 -- AAO554 BO 26 ------AAOS 61 BO 33 -- AAO562 (KIAAO562) BO 34 AAO563 (KIAAO563) BO 35 AAO569 (KIAAO569) BO 41 ------AA0571 (KIAA0571) BO 43 -- -- AAOS73 BO 45 -- -- AAOS76 BO 48 AAOS80 BO 52 AAOS84 BO 56 AAO592 BO 64 ------AAO596 BO 68 -- AA0598 (KIAAO598) BO 70 -- -- AAO608 BO 8O -- -- AA0614 BO 4514 ------AA0615 (KIAA0615) BO 4515 AAO621 BO 4521 -- -- AAO648 BO 4548 ------AAO652 (KIAA0652) BO 4.552 : ------AAO668 BO 4568 AAO669 BO 4569 AA0671 (KIAAO671) BO 4571 ------AAO675 (KIAAO675) BO 4575 -- -- AAO676 BO 4576 ------AAO677 (KIAAO677) BO 4577 ------AAO678 BO 4578 ------AAO679 BO 4579 ------US 2011/0003295 A1 Jan. 6, 2011 45
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu AA0680 (KIAAO680) BO1458O AAO692 BO14592 ------AAO697 BO14597 AAO699 BO14599 ------AAO700 BO14600 ------AAO737 (KIAA0737) FO14837 ------AA0748 (KIAA0748) BO18291 AA0763 (KIAAO763) BO18306 ------AA0769 (KIAAO769) BO18312 ------AAO782 BO1832S -- high in BPH stroma AAO796 BO18339 ------AAO798 (KIAAO798) BO18341 AAO823 BO2O630 AAO854 BO2O661 ------AAO856 BO2O663 ------AAO860 BO2O667 -- AAO862 FOS4828 -- -- AAO871 (non-exact 88%) BO2O678 AAO873 BO2O68O ------AAO892 B020699 ------AAO906 BO2O713 : ------AAO991 B023208.1 ler cell lectin-like receptor 1276 ------Subfamily B, member 1 (KLRB1) killer cell lectin-like receptor U96846 Subfamily C, member 4 (KLRC4) kinectin 1 (kinesin receptor) D13629 (KTN1) kinesin family member 5B X65873 -- -- (KIFSB) kinesin-like DNA binding ABO17430 ------protein Krueppel-related DNA M61869 binding protein (TF6) (low match) Kruppel related gene (clone pHKR1 RS) Kruppel-like Zinc finger US1869 protein Zf Kruppel-like Zinc finger U44975 protein Zf (non-exact 76%) kruppel-type Zinc finger ABO11414.1 protein, ZK1 Lapoferritin XO3742 actate dehydrogenase A XO2152 (LDHA) actate dehydrogenase A XO2152 (LDHA) (non-exact, 81%) actate dehydrogenase B X13794 high in fetal lung (LDHB) fibrablast actotransferrin (LTF) UO7643 high in bone marrow aminin binding protein (low D28372 score) aminin receptor 1 (67kD); X15005 high in many libraries Ribosomal protein SA (LAMR1) aminin receptor homolog 3 S35960 region} aminin, gamma 1 (formerly -- LAMB2) (LAMC1) atent transforming growth M34.057 actor beta binding protein 1 (LTBP1) LAZ3, BCL6 Z79581 (=Z79582: D28522/4) US 2011/0003295 A1 Jan. 6, 2011 46
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
LDLC 2 Z34975 ------ecithin-cholesterol 1 M17959 acyltransferase (LCAT) (non exact, 66%) ectin, galactoside-binding, 1 M87842 -- Soluble, 2 (galectin 2) (LGALS2) ectin, galactoside-binding, 1 L13210 ------Soluble, 3 binding protein (galectin 6 binding protein) (LGALS3BP) eucine rich repeat (in FLII) 5 AJ223075 -- interacting protein (LRRFIP1) eucocyte immunoglobulin 2 AFO72099 ike receptor-5 (LIR-5) eucocyte immunoglobulin 7 AFO25530 ike receptor-6a (LIR-6) eucocyte immunoglobulin 2 U82275 only found in CNS ike receptor-7 (LIR-7) eukemia virus receptor 1 1 L2O859 -- (GLVR1) eukocyte adhesion protein 1 M29484 p150.95 alpha subunit eukocyte antigen, HLA-A2 3 Y13267 eukocyte immunoglobulin 3 AFO2SS28 ike receptor (MIR-10) eukocyte tyrosine kinase 1 X6O702 -- found only in blood (LTK) eukocyte-associated Ig-like 3 AFO13249 receptor 1 (LIAR1) eukotriene A4 hydrolase 6 JO3459 -- (LTA4H) eupaxin (LDPL) AFO62O75 -- igase I, DNA, ATP 1 M36067 B, T dependent (LIG1) LIM and SH3 protein 1 2 X82456 -- (LASP1) LIM domain kinase 2 2 ACOO2O73 -- (LIMK2) ine-1 protein 1 Line-1 repeat mRNA with 2 1 U93566 -- open reading frames Line-1 repeat with 2 open 1 M22332 -- high in gastric tumor reading frames LINE-1 REVERSE 1 PO8547 TRANSCRIPTASE HOMOLOG ipase A, lysosomal acid, 4 X76488 ------cholesterol esterase (Wolman disease) (LIPA) ipase, hormone-sensitive 1 L117O6 -- -- (LIPE) LMP7 1 L11045 Lon protease-like protein X74215 ------(LONP) ow density lipoprotein 2 AFOS8414 -- only in liver related protein 1 (alpha-2- macroglobulin receptor) (LRP1) ow density lipoprotein 1 M63959 related protein-associated protein 1 (alpha-2- macroglobulin receptor associated protein 1) (LRPAP1) ow density lipoprotein 1 M63959 related protein-associated protein 1 (alpha-2- US 2011/0003295 A1 Jan. 6, 2011 47
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu macroglobulin receptor associated protein 1) (LRPAP1) (non-exact, 75%) ow-affinity Fc-gamma 1 LO8107 receptor IIA LPS-induced TNF-alpha 9 AFO10312 ------actor (PIG7) Lst-1 1 UOO921 ------L-type amino acid transporter 1 AF104032 subunit LAT1 ung resistance-related protein 1 X79882 ------(LRP) Lymphocyte antigen 75 1 AFO11333 B (LY75) ymphocyte antigen 9 (LY9) 2 L42621 ymphocyte antigen HLA- 2 L42345 B*44O2 and HLA-B*S101 ymphocyte cytosolic protein 42 JO2923 (L-plastin) (LCP1) ymphocyte cytosolic protein 4 U2O158 T lymphoma, 2 (SH2 domain-containing Tactivated eukocyte protein of 76 kD) (LCP2) ymphocyte glycoprotein 2 XO4391 -- -- T1. Leu-1 ymphocyte-specific protein 1 16 M33SS2 ------(LSP1) ymphocyte-specific protein 7 M36881 -- -- tyrosine kinase (LCK) ymphoid phosphatase LyP1 1 AFOO1847 ymphoid-restricted membrane 4 U10485 ------protein (LRMP) ymphoid-specific SP100 1 U36SOO -- homolog (LYSP100-A) ymphoma proprotein 2 U33849 ------convertase (LPC) LYSOSOMAL 1 P10619 PROTECTIVE PROTEIN PRECURSOR (CATHEPSIN A) (CARBOXYPEPTIDASE C) ysosomal-associated 1 JO4182 ------membrane protein 1 (LAMP1) Lysosomal-associated 1 JO41.83 ------membrane protein 2 (LAMP2) ysozyme (renal amyloidosis) 39 M19045 ------(LYZ) ysyl-tRNA synthetase 2 D32053 ------(KARS) Mphase phosphoprotein 10 1 X98494 (U3 Small nucleolar ribonucleoprotein) (MPP-10) M1-type and M2-type 2 XS6494 pyruvate kinase móA methyltransferase (MT- 7 AFO14837 ------A70) mab-21 (C. elegans)-like 1 1 U38810 ------(MAB21L1) MacMarcks 1 X70326 ------macrophage-associate 1 Z22968 ------antigen (MM130) MADS box transcription 1 U4902O ------enhancer factor 2, polypeptide A (myocyte enhancer factor 2A) (MEF2A) MADS box transcription 1 LO8895 ------enhancer factor 2, polypeptide C (myocyte enhancer factor 2C) (MEF2C) US 2011/0003295 A1 Jan. 6, 2011 48
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu major cytoplasmic tRNA- 1 X17516 Val(IAC) (=M33940) major histocompatibility 1 M95531 complex class I beta chain (HLA-B) major histocompatibility 41 Z93949 ------+ high in villous complex, class I, A (HLA-A) adenoma major histocompatibility 1 Z72422 complex, class I, A (HLA-A) (low match) major histocompatibility 82 M24097 ------complex, class I, C (HAL-C) major histocompatibility 77 M20022 ------complex, class I, E. (HLA-E) major histocompatibility 2 U15085 ------complex, class II, DM BETA (HLA-DMB) major histocompatibility 10 MS7466 ------complex, class II, DP beta 1 (HLA-DPB1) major histocompatibility 9 VOO522 ------complex, class II, DR beta 1 (HLA-DRB1) Major histocompatibility 2 M24O70 ------complex, class II, Ybox binding protein I; DNA binding protein B (YB1) malate dehydrogenase 1, NAD 1 DSS654 ------(soluble) (mdh1) malate dehydrogenase 1, NAD 3 D55654 ------(soluble) (MDH1) malonyl-CoA decarboxylase 2 AFO97832 precursor maltase-glucoamylase (mg) 1 AFO16833 -- manic fringe (Drosophila) 1 U94352 ------homolog (MFNG) mannose phosphate isomerase 1 X76057 ------(MPI) mannose phosphate isomerase 2 X76057 ------(mpi) mannose-6-phosphate receptor 3 X56253 ------(cation dependent) (M6PR) mannose-P-dolichol 1 AFO38961 ------utilitzation defect 1 (MPDU1) mannosidase, alpha B, 1 U60885 ------lysosomal (MANB) mannosyl (alpha-1,3-)- 1 MSS621 ------glycoprotein beta-1,2-N- acetylglucosaminyltransferase (MGAT1) map 4q35 repeat region 1 AFO 64849 MAP kinase-interacting 2 ABOOO409 ------serine/threonine kinase 1 (MKNK1) MAPERK kinase kinase 3 5 UT8876 -- (MEKK3) MAPERK kinase kinase 5 1 D84476 ------(MEKK5) MAP microtubule affinity- 4 M8O359 ------regulating kinase 3 (MARK3) Marenostrin protein 1 Y14441 MASL.1 1 ABO16816 MAX dimerization protein 3 LO6895 -- (MAD) MaxiKpotassium channel 1 AFO3SO46 beta subunit MBP-2 for MHC binding 1 X65644 ------protein 2 US 2011/0003295 A1 Jan. 6, 2011 49
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Meis (mouse) homolog 3 1 U6838S ------(MEIS3) melanoma-associated antigen 1 M12154 p97 (melanotransferrin) membrane cofactor protein 4 X594OS ------(CD46, trophoblast lymphocyte cross-reactive antigen) (MCP) membrane component, 4 D14696 ------chromosome 17, Surface marker 2 (ovarian carcinoma antigen CA125) (M17S2) membrane metallo- 2 JO3779 B ------endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10) (MME) membrane protein, 2 M64925 ------palmitoylated 1 (55 kD) (MPP1) meningioma expressed 1 U9478O -- antigen (MGEA) meningioma-expressed 1 U73682 ------antigen 11 (MEA11) Menkes Disease (ATP7A) 1 LO6133 -- putative Cu++-transporting P type ATPase metallothionein 2A (MT2A) 1 WOOS94 -- metaxin 1 (MTX1) 1 U46920 methionine 2 X68836 -- adenosyltransferase II, alpha (MAT2A) methyl-CpG binding domain 1 Y10746 protein 1 (MBD1) (non-exact 59% aa) methylene tetrahydrofolate 2 X16396 ------dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase (MTHFD2) methylenetetrahydrofolate 1 JO4.031 ------dehydrogenase (NADP+ dependent), methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase (MTHFD1) methyltransferase, putative 2 AJ224442 MHC antigen (HLA-B) U14943 (=L42024) HC class 1 region 2 AFOSSO66 HC class I antigen (HLA- U70863 MHC class I antigen (HLA- U19736
MHC class igen (HLA-C) U38975 MHC class an igen B*5801 US2813 (HLA-B) MHC class I antigen HLA-A 2 AFO15930 (HLA-A) MHC class I antigen HLA-A U36687 (HLA-A-2402 allele) MHC class I antigen HLA- 2 X13112 MHC class I antigen HLA-B U67331 (B*0801 variant) (=AF028596)
US 2011/0003295 A1 Jan. 6, 2011 51
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu MHC class IIHLA-DRB1 AFOOf883 MHC class IIHLA-DRW11- M21966 beta-I chain (DRw11.3) MHC class II lymphocyte M23907 antigen (DPW4-beta-1) MHC CLASS II P33076 TRANSACTIVATOR CIITA (non-exact 57%) MHC HLA-E2.1 (=X87679) M32507 MHC HLA-E2.1 (alpha-2 M32507 domain) (low match) Mi-2 autoantigen 240 kDa UO8379 protein (non-exact 84%) microsomal stress 70 protein UO4735 ATPase core (stch) microtubule-associated U19727 ------protein 4 (MAP4) microtubule-associated X73882 protein 7 (MAP7) mineralocorticoid receptor 2 M168O1 ------(aldosterone receptor) (MLR) minichromosome maintenance X62153 ------deficient (S. cerevisiae) 3 (MCM31) minichromosome maintenance ABO11144 ------deficient (S. cerevisiae) 3 associated protein (MCM3AP) minichromosome maintenance 2 X74795 ------deficient (S. cerevisiae) 5 (cell division cycle 46) (MCM5) mitochondiral cytochromeb 1 AFO42S17 (CYTB) mitochondrial 16S rRNA 11 Z70759 mitochondrial ATP synthase 2 XS9066 (F1-ATPase) alpha subunit mitochondrial ATP synthase c 1 X69907 subunit (P1 form) mitochondrial cytochromeb 6 AFO42508 (CYTB) mitochondrial cytochromeb 1 ABOO62O2 Small subunit of complex II mitochondria 1 POO395 CYTOCHROMEC OXIDASE POLYPEPTIDE I mitochondria 1 POO403
OXIDASE POLYPEPTIDE II mitochondrial cytochrome C 2 POO403 oxidase subunit II mitochondrial cytochrome S U12691 oxidase subunit II (COII) (=U12692 Hsa4 mitochondrion cytochrome oxidase subunit II) mitochondrial DNA loop 1 X89763 attachment sequences (clone mitochondrial DNA 1 U94703 -- polymerase accessory Subunit precursor (MtPolB) nuclear gene encoding mitochondrial protein, mitochondrial DNA, complete 1 X93334 genome mitochondrial genes for 8 VOO710 several tRNAs (Phe, Val, Leu) and 12S and 16S ribosomal RNAS. US 2011/0003295 A1 Jan. 6, 2011 52
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu mitochondrial genes for tRNA 3 WOO660 (Phe) and 12S rRNA (fragment) mitochondrial inner 1 AF106622 membrane preprotein translocase Tim17a mitochondrial isolate Afr7 1 AFO42SO3 cytochrome b(CYTB) mitochondrial loop attachment 1 X89843 sequence (clone LAS88) mitochondrial NADH 14 AFO14893 dehydrogenase subunit 2 (ND2) mitochondrial translational 1 L34600 ------initiation factor 2 (MTIF2) mitochondrion cytochromeb 1 UO9SOO mitogen inducible gene mig-2 1 Z24725 ------mitogen inducible gene mig-2 1 Z24725 (non-exact, 71%) mitogen-activated protein 2 U43784 ------kinase-activated protein kinase 3 (MAPKAPK3) MLNS1 2 X80199 ------MLN64 (=D38255 CAB1) 1 X801.98 ------moesin (MSN) 14 M69066 ------monocytic leukaemia zinc 2 U47742 ------finger protein (MOZ) MOP1 () 2 U2916S motor protein (Hs.78504) 2 D21094 ------mouse double minute 2, U39736 -- -- human homolog of p53 binding protein (MDM2) M-phase phosphoprotein 6 X98263 ------(MPP-6) M-phase phosphoprotein, X98260 mpp 11 MPS1 L2O314 Mr 110,000 antigen 2 D64154 ------MRCOX-2, V-like region XOS324 (=M17227) mu-adaptin-related protein-2: YO8387 musubunit of AP-4 (MU ARP2) multifunctional polypeptide X53793 ------similar to SAICAR synthetase and AIR carboxylase (ADE2H1) murine leukemia viral (bmi-1) L13689 ------oncogene homolog (BMI1) mutant (Daudi) beta2- 44 XO7621 microglobulin mutated in colorectal cancers M62397 ------(MCC) myeloid cell leukemia 9 LO8246 ------sequence 1 (BCL2-related) (MCL1) myeloid cell nuclear 11 M817SO -- -- differentiation antigeN (MNDA) myeloid differentiation 4 U70451 ------primary response gene (88) (MYD88) myeloid leukemia factor 2 3 U57342 ------(MLF2) myeloid/lymphoid or mixed- 8 U89867 ------lineage leukemia (trithorax (Drosophila) homolog): translocated to, 7 (MLLT7) US 2011/0003295 A1 Jan. 6, 2011 53
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu MYH9 (cellular myosin heavy 1 M811 OS chain) myomesin (M-protein)2 1 X69089 (165 kD) (MYOM2) myosin IE (MYO1E) 11 X984.11 -- -- myosin light chain kinase 1 U48959 ------(MLCK) myosin phosphatase, target 2 D8793O ------subunit 1 (MYPT1) myosin regulatory light chain 2 D50372 (=U26162) myosin VIIa (low match 71) 1 US5208 myosin, heavy polypeptide 9, 3 M811 OS ------non-muscle (MYH9) myosin, light polypeptide, 6 XS4304 ------regulatory, non-sarcomeric (20 kD) (MLCB) myosin-I beta 1 X98507 ------myristoylated alanine-rich 1 D10522 -- -- protein kinase C Substrate (MARCKS, 8OK-L) (MACS) myxovirus (influenza) 1 M3O817 ------resistance 1, homolog of murine (interferon-inducible protein p78) (MX1) myxovirus (influenza) 3 M3O818 -- resistance 2, homolog of murine (MX2) N-acetylgalactosaminidase, 2 M62783 ------alpha-(NAGA) N-acetylglucosamine receptor LO3S32 ------1 (thyroid) (NAGR1) NACP/alpha-synuclein 2 U46896 N-acylaminoacyl-peptide D38441 ------hydrolase (APEH) N-acylsphingosine 11 U47674 ------amidohydrolase (acid ceramidase) (ASAH) NAD+-specific isocitrate U49283 ------dehydrogenase beta Subunit precursor (encoding mitochondrial protein) NADH dehydrogenase US3468.1 ------(ubiquinone) 1 alpha Subcomplex, 5 (13 kD, B13) (NDUFAS) NADH dehydrogenase AFO47181 ------(ubiquinone) 1 beta Subcomplex, 5 (16 kD, SGDH) (NDUFB5) NADH dehydrogenase AFOSO640 ------(ubiquinone) Fe—S protein 2 (49 kD) (NADH-coenzyme Q eductase) (NDUFS2) NADH dehydrogenase M22S38 ------(ubiquinone) flavoprotein 2 (24 kD) (NDUFV2) NADH:ubiquinone 2 AFOS3070 ------dehydrogenase 51 kDa subunit (NDUFV1) NADH-CYTOCHROMEBS 1 POO387 REDUCTASE (BSR) (50%aa) NADH-UBIQUINONE 1 PO3886 OXIDOREDUCTASE CHAIN 1 Nardilysin (N-arginine dibasic 2 U64898 ------convertase) (NRD1) US 2011/0003295 A1 Jan. 6, 2011 54
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu nascent-polypeptide- S X80909 ------associated complex alpha polypeptide (NACA) natural killer cell group 7 8 S6911S -- -- sequence (NKG7) natural killer cell transcript 4 19 M32011 -- (NK4) natural killer-associated 1 U3O274 -- blood only transcript 3 (NKAT3) natural killer-associated 1 AFO22045 -- blood only transcript 5 (NKAT5) natural killer-tumor 1 LO4288 B ------recognition sequence (NKTR) N-deacetylase/N- 2 AFO42O84 ------Sulfotransferase (heparan glucosaminyl)2 (NDST2) Ndr protein kinase 3 Z3S102 -- Nedd-4-like ubiquitin-protein 1 U961.13 ligase WWP1 nel (chicken)-like 2 (NELL2) 3 D83018 -- -- N-ethylmaleimide-sensitive 1 U39412 -- -- factor attachment protein, alpha (NAPA) N-ethylmaleimide-sensitive 1 UT8107 ------factor attachment protein, gamma (NAPG) neural precursor cell 3 X92S44 ------+ high in testis expressed, developmentally down-regulated 5 (NEDD5) neural precursor cell D23662 ------expressed, developmentally down-regulated 8 (NEDD8) neuregulin 1 (NRG1) UO2330 ------neuroblastoma RAS viral (v- 4 ABO2O692 ------ras) oncogene homolog (NRAS) Neuroblastoma RAS viral (v- X68286 ras) oncogene homolog (NRAS) (low match) Neurofibromin 2 (bilateral S73853 -- -- acoustic neuroma) (NF2) neuronal apoptosis inhibitory 2 U19251 ------protein (NAIP) neuronal cell adhesion ABOO2341 ------molecule (NRCAM) neuropathy target esterase AJOO4832 ------(NTE) neuropeptide Y3 receptor, D284.33 5'UTR (low score) neurotrophic tyrosine kinase, 14 XO3S41 ------receptor, type 1 (NTRK1) neutrophil cytosolic factor 4 2 USO720 (40 kD) NG31 1 AF129756 NGAL (=X83006) 1 X991.33 nibrin (NBS) 1 AFOS1334 NIK 1 ABO14587 ------Ninjurin 1: nerve injury- 1 U72661 ------induced protein-1 nitrilase 1 (NIT1) 1 AFO6998.7 (=AFO69984) NKG2-D (low match) (non- 1 XS4870 exact, 58%) Nmi 1 U32849 N-myristoyltransferase 1 1 AFO43324 ------(NMT1) No arches-like (Zebrafish) 1 UT9569 ------Zinc finger protein (NAR) US 2011/0003295 A1 Jan. 6, 2011 55
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu non-histone chromosome 1 DSO42O ------protein 2 (S. cerevisiae)-like 1 (NHP2L1) non-muscle (fibroblast) 1 tropomyosin non-muscle alpha-actinin 1 U48734 non-muscle myosin alkali 3 M22918 ------+ High in fetal adrenal light chain (Hs.77385) gland and BPH stroma non-neuronal enolase (EC 1 X16289 4.2.1.11) non-receptor tyrosine 1 M33689 phosphatase 1 normal keratinocyte 3 X53778 ------+ high in many libraries Substraction library mRNA, clone H22a notch group protein (N) 3 M99437 novel protein 1 X999.61 novel T-cell activation protein 1 X94232 ------N-ras protein NRU 1 A6O196 N-sulfoglucosamine 1 U6O111 -- -- Sulfohydrolase (sulfamidase) (SGSH) insulin induced gene 1 1 U96876 ------(INSIG1) integrin, alpha 4 (antigen 3 L12002 -- -- CD49D, alpha 4subunit of VLA-4 receptor) (ITGA14) interferon, gamma-inducible 1 M63838 ------protein 16 (IFI16) interleukin 1, beta (IL1RB) 1 M15330 nuclear antigen H731-like 2 U83908 ------protein nuclear antigen Sp100 4 U36SO1 ------(SP100) Nuclear antigen Sp100 1 P23497 (SP100) (85% aa) Nuclear antigen Sp100 1 P23497 (SP100) (89% aa) nuclear autoantigenic sperm 1 M97856 -- -- protein (histone-binding) (NASP) nuclear corepressor KAP-1 1 U78773 (KAP-1) (=U95040; X97548 TIF1beta zinc finger protein) Nuclear domain 10 protein 4 U22897 ------(NDP52) Nuclear factor (erythroid- 1 S74O17 ------derived 2)-like 2 (NFE2L2) Nuclear factor of kappa light 2 MS8603 ------polypeptide gene enhancer in B-cells 1 (p105) (NFKB1) nuclear factor of kappa light 3 M69043 ------polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA) nuclear factor related to kappa 1 UO8.191 ------B binding protein (NFRKB) nuclear mitotic apparatus 3 Z11S83 ------protein 1 (NUMA1) nuclear receptor coactivator 2 1 X97674 (GRIP1) nuclear receptor coactivator 3 2 AFO10227 ------(AIB3) nuclear receptor coactivator 4 22 X77548 ------(ELE1) nuclear receptor interacting 1 X84373 ------protein 1 (NRIP1) nuclear respiratory factor 1 1 UO2683 B -- -- US 2011/0003295 A1 Jan. 6, 2011 56
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu nuclear RNA helicase, DECD 4 U90426 ------variant of DEAD box family (DDXL) nuclear transcription factor Y, X59711 B alpha (NFYA) nuclear transcription factor, 3 U15306 ------X-box binding 1 (NFX1) nuclear transport factor 2 XO7315 ------(placental protein 15) (PP15) nucleobindin (=M96824) U31336 nucleobindin 1 (NUCB1) 2 M96824 ------nucleolar phosphoprotein Z34289 -- -- p130 (P130) nucleolar protein (KKED Y12O65 ------repeat) (NOP56) nucleolar protein (MSP58) AFO15308 nucleolar protein 1 (120 kD) M32110 -- -- (NOL1) nucleolar protein p40 U866O2 ------nucleolin (NCL) 2 M60858 ------nucleophosmin (nucleolar 14 M28699 ------phosphoprotein B23, numatrin) (NPM1) nucleophosmin-retinoic acid U41742 receptor alpha fusion protein NPM-RAR long form nucleoporin (NUP358) 2 L41840 (=D42063 RanBP2 (Ran binding protein 2)) nucleoporin 153 kD (NUP153) Z25535 nucleoporin 98 kD (NUP98) U41815 nucleosome assembly protein D28430 nucleosome assembly protein M866.67 ------1-like 1 (NAP1L1) nucleosome assembly protein 2 UT 7456 ------1-like 4 (NAP1L4) nucleosome assembly protein, D28430 5UTR olfactory receptor (OR7-141) U86281 OLFACTORY RECEPTOR- P34982 LIKE PROTEIN HGMPO7E (OR17-4) (non-exact 65%) oligodendrocyte myelin 7 LO5367 -- glycoprotein (OMG) O-linked N-acetylglucosamine U77413 ------(GlcNAc) transferase (UDP N acetylglucosamine:polypeptide N-acetylglucosaminyl transferase) (OGT) oncofetal trophoblast 1 AS3531 glycoprotein 5T4 precursor (non-exact 55%) Oncogene TIM (TIM) (non- 1 UO2O82 exact 84%) ORF (Hs.77868) 1 M68864 ------ORF1; MER37; putative 1 U49973 transposase similar to pogo element Length = 454 origin recognition complex, 2 U27459 -- Subunit 2 (yeast homolog)-like (ORC2L) origin recognition complex, 1 AFO22108 Subunit 4 (yeast homolog)-like (ORC4L) (low match) ornithine aminotransferase 2 M23204 ------(gyrate atrophy) (OAT) US 2011/0003295 A1 Jan. 6, 2011 57
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu ornithine decarboxylase M2O372 (ODC) ornithine decarboxylase 11 D78.361 ------+ High in pancreas, and antizyme, ORF1 and ORF2 activated T cells orphan receptor (Hs.100221) 2 UO7132 ------OS-9 precurosor 6 ABOO2806 ------osteonectin (=X82259 BM- D28381 40) ovel centrosomal protein ABOO8515 ------RanBPM (RANBPM) over-expressed breast tumor L34839 protein Oviductal glycoprotein 1, UO9550 ------120 kD (OVGP1) oxidase (cytochrome c) X80695 ------assembly 1-like (OXAIL) oxoglutarate dehydrogenase 4 D10523 T ------(lipoamide) (OGDH) oxysterol binding protein M86917 ------(OSBP) OZF X70394 ------OZF (non-exact zinc finger) X70394 p21 iCdc42, Rac1-activated 2 US 1120 ------kinase 1 (yeast Ste20-related) (PAK1) P35-related protein (=S80990 D63392 icolin) 340 U93569 p40phox (=U50720) X77094 P47 LBC oncogene 4 UO3634 p53-induced protein (PIG11) AFO10315 ------p54.nrb (low match) Y11287 p62 nucleoporin X58521 b63 mRNA for X6991O ------transmembrane protein PAC clone DJO701O16 from Q07108 7q33-q36 (non-exact 54%) palmitoyl-protein thioesterase 10 U44772 ------(ceroid-lipofuscinosis, neuronal 1, infantile; Haltia Santavuori disease) (PPT) papillary renal cell carcinoma X9972O ------(translocation-associated) (PRCC) PAR protein AF115850 -- -- partial EST (clone c-1gh O4) Z43627 PAX3, forkhead transcription UO2368 actor gene fusion paxillin (PXN) 4 D86862 ------PBK1 protein 2 AJOO7398 ------PBS-EST (nz92e01.s1 AA732534 NCI CGAP GCB1 clone MAGE: 1302936) (low score) PDZ domain protein AJ224747 ------(Drosophila inaD-like) (INALD) PEBP2aCRunt domain Z38108 encoding gene (=Z35728) peptidase D (PEPD) JO4605 peptidylprolyl isomerase A 3 YOOO52 ------+ high in many libraries (cyclophilin A) (PPIA) peptidylprolyl isomerase D 2 L11667 T ------(cyclophilin D) (PPID) peptidylprolyl isomerase E 1 AFO42386 ------(cyclophilin E) (PPIE) PERB11.1 (=U56942 MHC 1 U69630 class I chain-related protein A) US 2011/0003295 A1 Jan. 6, 2011 58
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu perforin 1 (preforming 14 M28393 protein) (PRF1) peroxisomal acyl-CoA 2 X86032 hioesterase (PTE 1) Peroxisomal acyl-coenzyme A 1 X71440 -- -- oxidase peroxisomal fairnesylated 1 X75535 -- -- protein (PXF) phorbol-12-myristate-13 1 D9007O B, W acetate-induced protein (PMAIP1) phosphate carrier 1 X77337 (mitochondrial gene'?) Phosphate carrier, 3 X60O36 -- -- mitochondrial (PHC) phosphate cytidylyltransferase 1 L28957 T -- , choline, alpha isoform (PCYT1A) PHOSPHATIDATE 1 Q92903 CYTIDYLYLTRANSFERASE (CDP-DIGLYCERIDE) phosphatidylinositol 3-kinase 2 US 7843 delta catalytic Subunit phosphatidylinositol 4-kinase, 3 ABOO5910 - -- catalytic, beta polypeptide
hosphatidylinositol glycan, 1 L19783 -- --
phatidylinositol transfer 2 D30O37 rotein (PI-TPbeta) hosphatidylinositol transfer 2 X98.654 B, T rotein, membrane-associated lymphoma PITPNM) hosphatidylinositol transfer X98.654 O ein, membrane-associated PNM) (non-exact 64%) hosphatidylinositol-4- U14957 -- hosphate 5-kinase, type II, pha (PIP5K2A) hosphatidylinositol-4- U85.245 -- hosphate 5-kinase, type II, eta (PIP5K2B) phosphodiesterase 7A L12052 B, W -- (PDE7A) phosphodiesterase IB U56976 ONLY (PDES1B) phosphoglucomutase 1 2 M83O88 -- (PGM1) phosphogluconate U3O255 dehydrogenase (PGD) phosphoglycerate kinase 1 12 VOO572 (PGK1) phosphoglycerate mutase 1 3 JO4173 ------(brain) (PGAM1) phosphoglycerate mutase 2 1 M55673 (muscle) (PGAM2) phosphoinositide-3-kinase, 1 Z29090 -- catalytic, alpha polypeptide (PIK3CA) phosphoinositide-3-kinase, 4 U86453 -- catalytic, delta polypeptide (PIK3CD) phosphoinositide-3-kinase, 1 X83368 catalytic, gamma polypeptide (PIK3CG) phospholipase C 1 X14034 phospholipase C, delta 1 2 UO9117 -- (PLCD1) US 2011/0003295 A1 Jan. 6, 2011 59
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu phospholipase C, gamma 1 1 M34667 ------(formerly subtype 148) (PLCG1) phospholipid scramblase 1 AFOO8445 phosphoribosyl 1 D61391 pyrophosphate synthetase associated protein 1 (PRPSAP1) phosphoribosylglycinamide 3 XS41.99 ormyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase (GART) phosphorylase kinase, alpha 2 3 D38616 (liver), glycogen storage disease IX (PHKA2) hosphorylase, glycogen; 1 U47O2S ------rain (PYGB) hosphorylase, glycogen; 1 U47O2S rain (PYGB) (low match, on-exact, 75%) hosphorylase, glycogen; liver 1 Y15233 ------Hers disease, lycogen storage isease type VI) (PYGL) hosphorylation regulatory 2 -10 hosphotidylinositol transfer D3.0036 ------protein (PITPN) pigment epithelium-derived U29953 -- actor (PEDF) pim-1 oncogene (PIM1) M24779 ------pinin, desmosome associated U77718 B, monocyte, protein (PNN) T lymphoma placenta (Diff33) S U491.88 ------placenta (Diff33) (non-exact, U491.88 69%) placenta (Diff48) 18 U491.87 -- placenta (Diff48) (low match) U491.87 placenta (Diff48) (low match) U491.87 asminogen activator, X74039 -- -- l rokinase receptor (PLAUR) elet factor 4 (PF4) M25897 -- -- eletendothelial cell 8 M37780 ------8. dhesion molecule (CD31 ntigen) (PECAM1) platelet-activating factor 4 U89386 acetylhydrolase 2 (40 kD) (PAFAH2) platelet-activating factor 1 U72342 -- acetylhydrolase, isoform lb., alpha subunit (45 kD) ( 8. elet-activating factor 1 D102O2 -- eceptorC (PTAFR) e ckstrin (PLEK) 10 XO7743 ------e ckstrin (PLEK) (low 1 XO7743 8. ch) e ckstrin homology, Sect 4 M85169 ------coiled coil domains 1 (cytohesinC 1) (PSCD1) eckstrin homology, Sect 4 LO6633 -- -- 8 coiled coil domains, binding protein (PSCDBP) pM5 protein 1 X57398 ------PMP69 Y14322 poly (ADP-ribose) polymerase 1 X56140 (NAD(+) ADP ribosyltransferase) (=X16674) US 2011/0003295 A1 Jan. 6, 2011 60
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu poly(A) polymerase (PAP) X76770 ------poly(A)-binding protein-like 1 19 YOO345 : : ------(PABPL1) poly(rC)-binding protein 1 3 X78137 -- -- (PCBP1) polyadenylate binding protein U75686 polycystic kidney disease 1 S U24498 (autosomal dominant) (PKD1) polymerase (DNA directed), D29013 -- beta (POLB) polymerase (DNA directed), 6 D84103 gamma (POLG) polymerase (RNA) II (DNA X63564 -- -- directed) polypeptide A (220 kD) (POLR2A) polymyositis, scleroderma LO1457 -- -- autoantigen 2 (100 kD) (PMSCL2) polypyrimidine tract binding X65372 -- -- protein (heterogeneous nuclear ribonucleoprotein I) (PTB) positive regulator of 3 U13021 programmed cell death ICH 1L (Ich-1) postmeiotic segregation 1 M16514 -- -- increased 2-like 12 (PMS2L12) postmeiotic segregation 1 U38964 -- -- increased 2-like 8 (PMS2L8) potassium inwardly-rectifying 1 D87291 -- channel, Subfamily J, member 5 (KCNJ15) potassium voltage-gated 1 AFOS1426 -- channel, KQT-like subfamily, member 1 (KCNQ1) POU domain, class 2, 1 Z491.94 -- associating factor 1 (POU2AF1) POU domain, class 2, 2 X13403 -- transcription factor 1 (POU2F1) PPAR binding protein Y13467 -- (PPARBP) PPARgamma2 D83233 pre-B-cell colony-enhancing 8 UO2O20 actor (PBEF) prefoldin 1 (PFDN1) Y17392 -- -- prefoldin 5 (PRFLD5) 3 D89667 B : : -- prefoldin subunit 3 (=U96759 Y17394 von Hippel-Lindau binding protein (VBP-1)) pregnancy-associated plasma U28727 -- high in placenta protein A (PAPPA) pre-mRNA splicing factor UO881S -- SF3a (60 kD), similar to S. cerevisiae PRP9 (spliceosome-associate protein 61) (SF3A60) pre-mRNA splicing factor UO881S SF3a (60 kD), similar to S. cerevisiae PRP9 (spliceosome-associate protein 61) (SF3A60) (low score) pre-mRNA splicing factor 2 D28423 SRp20, 5' UTR preprotein translocase 3 X97544 -- (TIM17) US 2011/0003295 A1 Jan. 6, 2011 61
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu prion protein 1 X82S45 prion protein (p27-30) 1 M13899 ------(Creutzfeld-Jakob disease, Gerstmann-Strausler Scheinker syndrome, fatal amilial insomnia) (PRNP) pristanoyl-CoA oxidase (low 1 Y11411 match) pristanoyl-CoA oxidase (low 1 Y11411 score) procollagen-lysine, 2- 1 M982S2 ------oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers Danlos syndrome type VI) (PLOD) procollagen-proline, 2- 1 M24486 ------oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide 1 (P4HA1) procollagen-proline, 2- 4 XOS130 ------oxoglutarate 4-dioxygenase (proline 4-hydroxylase), beta polypeptide (protein disulfide isomerase; thyroid hormone binding protein p55) (P4HB) profilin 1 (PFN1) 1 JO3.191 ------progesterone receptor- 2 U28918 -- associated p48 protein (P48) prohibitin (PHB) 1 S85655 ------proliferating cell nuclear 3 JO4718 ------antigen (PCNA) proliferation-associated gene 4 L1918.4 ------A (natural iller-enhancing actor A) (PAGA) proline-rich protein BstNI 1 S62936 Subfamily 2 (PRB2) (non exact, 43% aa) proline-serine-threonine 1 U94778 phosphatase interacting protein 1 (PSTPIP1) prolyl endopeptidase (PREP) 2 X74496 prolylcarboxypeptidase 5 L13977 : -- : -- : (angiotensinase C) (PRCP) promyelocytic leukemia 1 M80185 ------(PML) properdin P factor, 4 XS7748 -- complement (PFC) pro-platelet basic protein 1 M54995 ------(includes platelet basic protein, beta hromboglobulin, connective issue-activating peptide III, neutrophil-activating peptide 2) (PPBP) pro-platelet basic protein 7 M54995 ------(includes platelet basic protein, beta hromboglobulin, connective issue-activating peptide III, neutrophil-activating peptide 2) (PPBP) proprotein convertase 4 U40623 Subtilisin?kexin type 7 (PCSK7) prosaposin (variant Gaucher 89 DOO422 ------disease and variant metachromatic eukodystrophy) (PSAP) US 2011/0003295 A1 Jan. 6, 2011 62
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu prostaglandin-endoperoxide 1 U63846 B ------synthase 1 (prostaglandin GH synthase and cyclooxygenase) (PTGS1) prostaglandin-endoperoxide 2 L15326 synthase 2 (prostaglandin GH synthase and cyclooxygenase) (PTGS2) prostaglandin-endoperoxide 1 D64O68 synthase-1 (=L08404; U84208) (all promoters) prostate carcinoma tumor 2 L78132 antigen (pcta-1) protease inhibitor 1 (anti- 17 KO2212 ------+ high in many libraries elastase), alpha-1-antitrypsin (PI) protease inhibitor 2 (anti- 1 M930S6 -- -- elastase), monocyte/neutrophil (ELANH2) (low match) proteasome prosome, 3 LO2426 B ------macropain) 26S subunit, ATPase, 1 (PSMC1) proteasome prosome, 1 M34O79 ------macropain) 26S subunit, ATPase, 3 (PSMC3) proteasome prosome, 2 AFO2O736 macropain) 26S subunit, ATPase, 4 (PSMC4) proteasome prosome, S L38810 ------macropain) 26S subunit, ATPase, 5 (PSMC5) proteasome prosome, 2 D78275 ------macropain) 26S subunit, ATPase, 6 (PMSC6) proteasome prosome, 1 AFOO1212 T -- -- macropain) 26S subunit, non ATPase, 11 (PSMD11) proteasome prosome, 2 D781.51 ------macropain) 26S subunit, non ATPase, 2 (PSMD2) proteasome prosome, 1 S79862 T ------macropain) 26S subunit, non ATPase, 5 (PSMD5) proteasome prosome, 1 DSOO63 ------+ high in many libraries macropain) 26S subunit, non ATPase, 7 (Mov34 homolog) (PMSD7) proteasome prosome, 1 ABOO3103 ------macropain) 26S subunit, on ATPase, 12 (PMSD12) proteasome prosome, 3 LO7633 ------macropain) activator Subunit 1 (PA28 alpha) (PSME1) proteasome prosome, 2 DOO762 ------macropain) subunit, alpha type, 3 (PSMA3) proteasome prosome, 3 X61970 ------macropain) subunit, alpha type, 5 (PSMA5) proteasome prosome, 3 AFOS418S ------macropain) subunit, alpha type, 7 (PSMA7) proteasome prosome, 1 AFO22815 macropain) subunit, alpha type, 7 (PSMA7) (low match) proteasome prosome, 1 DOO761 ------macropain) subunit, beta type, (PSMB1) US 2011/0003295 A1 Jan. 6, 2011 63
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu proteasome prosome, 1 X71874 ------macropain) subunit, beta type, 10 (PSMB10) proteasome prosome, 1 D29012 ------macropain) subunit, beta type, 6 (PMS proteasome prosome, 1 U17497 ------macropain) subunit, beta type, 8 (large multifunctional protease 7) (PSMB8) proteasome prosome, 3 Z14977 ------macropain) subunit, beta type, 9 (large multifunctional protease 2) (PSMB9) proteasome prosome, 1 D38048 -- -- macropain) subunit, beta ype, 7 (PSMB7) protective protein for beta 3 M22960 -- -- galactosidase (galactosialidosis) (PPGB) protein A alternatively spliced 1 U47925 -- orm 2 (A-2) protein activator of the 1 AFO72860 -- high in testis interferon-induced protein kinase (PACT) protein disulfide isomerase 2 D494.89 -- -- related protein (P5) Ocil 1 L25441 -- -- geranylgeranyltransferase type , beta subunit (PGGT1B) protein homologous to 20 M24.194 -- -- high in many libraries chicken B complex protein, guanine nucleotide binding (H12.3) protein kinase Aanchoring 1 AFO37439 -- protein protein kinase C substrate 2 USO317 ------protein kinase C, beta 1 6 XO6318 ------(PRKC B1) protein kinase C, delta 1 D10495 ------(PRKC D) protein kinase C, eta 1 MSS284 -- -- (PRKC H) protein kinase C, mu 1 X75756 (PRKCM) (non-exact 78%) C rotein kinase C-like 1 2 D26181 ------L1) protein kinase, AMP 1 U42412 B, T -- -- activated, gamma 1 non lymphoma catalytic subunit (PRKAG1) protein kinase, cAMP 4 M18468 -- dependent, regulatory, type I, alpha (tissue specific extinguisher 1) (PRKAR1A) protein kinase, DNA 1 U47077 ------activated, catalytic polypeptide (PRKDC) protein kinase, mitogen 1 Z11695 B -- -- activated 1 (MAP kinase 1: p40, p4 ) (PRKM1) protein kinase, mitogen 1 L77964 ------activated 6 (extracellular signal-regulated kinase, p97) (PRKM 6) protein kinase, mitogen 1 U66839 ------activated, kinase 3 (MAP kinase kinase 3) (PRKMK3) US 2011/0003295 A1 Jan. 6, 2011 64
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu protein phosphatase 1, S. M63960 ------catalytic Subunit, alpha isoform (PPP1CA) protein phosphatase 1, 3 Y13247 ------regulatory Subunit 10 (PPPR10) protein phosphatase 1, 2 ZSO749 ------regulatory Subunit 7 (PPP1R7) protein phosphatase 2 1 X12656 ------(formerly 2A), catalytic subunit, beta isoform (PPP2CB) protein phosphatase 2 1 LO7590 ------(formerly 2A), regulatory subunit B" (PR 72), alpha isoform and (PR130), beta isoform (PPP2R3) protein phosphatase 2, 2 L42373 ------regulatory subunit B (B56), alpha isoform (PPP2R5A) protein phosphatase 2, 3 D7836O ------regulatory subunit B (B56), delta isoform (PPP2R5D) protein phosphatase 2, 1 D26445 ------regulatory subunit B (B56), gamma isoform (PPP2R5C) protein phosphatase 2A S. JO2902 ------regulatory Subunit alpha isotype (alpha-PR65) protein phosphatase 4 2 AFO97996 ------(formerly X), catalytic subunit ( protein tyrosine kinase 2 beta 4 L492O7 ------(PTK2B) protein tyrosine phosphatase 1 XS4134 epsilon protein tyrosine phosphatase 2 L48723 ------type IVA, member 2
rotein tyrosine hosphatase, 1 M31724 ------on-receptor typ 1 (PTPN1) rotein tyrosine hosphatase, 1 M93425 ------+ high in testis on-receptor typ 12 PTPN12) rotein tyrosine phosphatase, 1 M93425 on-receptor type 12 PTPN12) (non-exact, 70%) O e l lyrO S. l e hosphatase, 2 M2S393 ------2 (PTPN2) hosphatase, 1 M68941 ------(megakaryocyte) (PTPN4) ine phosphatase, 7 M74903 ------non-receptor type 6 (PTPN6) ine phosphatase, 1 D11327 ------non-receptor type 7 (PTPN7) protein tyrosine phosphatase, 1 M34668 ------receptor type, alpha polypeptide (PTPRA) protein tyrosine phosphatase, 44 YOO638 ------receptor type, c polypeptide (PTPRC) protein tyrosine phosphatase, 1 X58288 ------receptor type, M (PTPRM) protein tyrosine phosphatase, 2 U81561 ------receptor type, N polypeptide 2 (PTPRN2) US 2011/0003295 A1 Jan. 6, 2011 65
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu protein with polyglutamine 1 U94836 ------repeat (ERPROT213-21) protein-kinase, interferon 1 U28424 ------inducible double stranded RNA dependent inhibitor (PRKRI) protein-L-isoaspartate (D- D13892 aspartate) O-methyltransferase (PCMT1) proteoglycan 1, secretory JO3223 granule (PRG1) prothymosin, alpha (gene 12 M14483 -- sequence 28) (PTMA) prp.28, U5 snRNP 100 kod AFO264O2 ------protein (U5-10OK) PRP4/STK/WD splicing AFOO1687 ------actor (HPRP4P) PTK7 protein tyrosine kinase U4O271 ------7 (PTK7) purinergic receptor P2X, AFOOO234 ------igand-gated ion channel, 4 (P2RX4) purinergic receptor P2X, Y12851 -- macrophage only igand-gated ion channel, 7 (P2RX7) puromycin-sensitive YO7701 -- -- aminopeptidase (PSA) putative ATP(GTP)-binding AJO10842 -- protein putative brain nuclearly ABO183O8 ------argeted protein (KIAAO765) putative chemokine receptor; D10923 -- GTP-binding protein (HM74) putative dienoyl-CoA AFO3O249 isomerase (ECH1) putative G-binding protein AFO65393 Putative human HLA class II U73477 B -- associated protein I (PHAP1) Putative L-type neutral amino ABOO7896 acid transporter (KIAA0436) putative mitochondrial space AFOSO198 protein 32.1 PUTATIVEMUCIN CORE Q04900 PROTEIN PRECURSOR 24 (MULTI-GLYCOSYLATED CORE PROTEIN 24) (MGC 24) (MUC-24) putative nucleic acid binding X763O2 ------protein putative outer mitochondrial U58970 ------membrane 34 kDa translocase Htom34 putative p150 (non-exact U93568 88%) putative translation initiation L26247 -- High in moderately actor (SUI1) differentiated colon adenocarcinoma putative tumor Suppressor AFO61836 protein (123F2) pyrroline 5-carboxylate M77836 -- reductase pyruvate dehydrogenase D90O84 (lipoamide) alpha 1 (PDHA1) pyruvate dehydrogenase JO3576 -- (lipoamide) beta (PDHB) Pyruvate dehydrogenase Y1314.5 complex, lipoyl-containing component X; E3-binding protein (PDX1) US 2011/0003295 A1 Jan. 6, 2011 66
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu pyruvate kinase, muscle 11 M23725 -- (PKM2) RAB, member of RAS 1 U1842O ------oncogene family-like (RABL) RAB1, member RAS 3 M28209 ------oncogene family (RAB1) RAB11A, member RAS 2 XS6740 ------+ high in spleen oncogene family (RAB11A) RAB11B, member RAS 1 D45418 -- -- oncogene family (Rab11B) RAB27A, member RAS 3 U38654 -- oncogene family (RAB27A) RAB5B, member RAS 1 XS4871 ------oncogene family (RAB5B) RAB6, member RAS 1 M28.212 -- -- oncogene family (RAB6) RAB7, member RAS 1 X934.99 ------oncogene family (RAB7) RAB7, member RAS 2 D84488 ------oncogene family-like 1 RAB9, member RAS 1 U44103 oncogene family (RAB9) RAD50 (S. cerevisiae) 2 U63139 ------homolog (RAD50) RAD51 (S. cerevisiae) 1 AFO29669 ------homolog C (RAD51C) Radin blood group (RD) 2 LO3411 ------RAE1 (RNA export 1, 3 U84720 ------S. pombe) homolog (RAE1) ralA-binding protein 2 L42542 ------(RLIP76) RAN binding protein 2-like 1 2 AFO12086 (RANBP2L1) Ran GTPase activating protein 3 X82260 ------(RANGAP1) RAN, member RAS oncogene 1 M31469 amily (RAN) (low match) RanBP2 (Ran-binding protein 1 D42063 2) (=U19248; L41840 sapiens nucleoporin (NUP358)) ransforming growth factor, 4 DSO683 ------beta receptor II (70-80 kD)
RAP1A, member of RAS 10 M22995 ------oncogene family (RAP1A) RAR-related orphan receptor 1 U16997 -- C (RORC) RAS guanyl releasing protein 1 Y12336 -- -- 2 (calcium and DAG regulated) ras homolog gene family, 12 XOSO26 ------+ high in ovary member A (ARHA) ras homolog gene family, 1 X61587 ------member G (rho G) (ARHG) ras homolog gene family, 2 Z35227 ------member H (ARHH) ras inhibitor (RIN1) 2 M37191 -- Ras-GTPase activating protein 2 AFO53535 ------SH3 domain-binding protein 2 (KIAAO660) Ras-GTPase-activating 3 U32519 ------protein SH3-domain-binding protein (G3BP) ras-related C3botulinum 11 M29871 -- -- toxin substrate 2 (rho family, Small GTP binding protein Rac2) (RAC2) US 2011/0003295 A1 Jan. 6, 2011 67
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
RAS-RELATED PROTEIN 1 PO9526 RAP-1B (GTP-BINDING PROTEIN SMG P21B) RBQ- 1 X851.33 ------rearranged T cell receptor beta 1 LO6891 variable region (TCRB) (=X58810) regulator of Fas-induced 1 AFO57557 B -- apoptosis (TOSO) regulator of G protein 1 AFO7392O -- signalling 6 (RGS6) regulator of G-protein 2 AFO37195 ------signalling 14 (RGS14) regulator of G-protein 6 L13391 ------signalling 2, 24 kD (RGS2) regulator of G-protein 1 O15539 signalling 5 (RGS5) (49% aa) regulatory factor X, 4 1 M69297 -- -- (influences HLA class II expression) (RFX4) regulatory factor X, 5 2 X85786 T ------(influences HLA class II expression (RFX5) replication protein A1 1 M63488 ------(RPA1) replication protein A3 (14 kD) 1 LO7493 (RPA3) (low match) reproduction 8 (D8S2298E) 1 D83767 ------requiem, apoptosis response 2 U94585 ------Zinc finger gene (REQ) requiem, apoptosis response 1 U94585 Zinc finger gene (REQ) (=AF001433) (low match) restin (Reed-Steinberg cell- 1 M975O1 B, T -- -- expressed intermediate filament-associated protein) (RSN) retinoblastoma 1 (including 3 L11910 ------osteosarcoma) (RB1) retinoblastoma binding AFO87481 protein 2 homolog 1 (RBBP2H1) retinoblastoma-binding S66427 -- -- protein 1 (RBBP1) retinoblastoma-binding S S66431 ------protein 2 (RBBP2) retinoblastoma-binding X71810 ------protein 4 (RBBP4) retinoblastoma-binding X74262 ------protein 4 (RBBP4) retinoblastoma-binding U3S143 protein 7 (RBBP7) retinoblastoma-like 2 (p130) X76061 ------(RBL2) retinoic acid receptor AFO)6O228 ------responder (tazarotenenduced) 3 (RARRES3) retinoic acid receptor, alpha XO6538 ------(RARA) retinoic acid responsive USO383 ------(NN8-4AG) retinoid X receptor beta 2 X66424 ------(RXR-beta) REV3H (yeast homolog)-like, AFO35537 catalytic subunit of DNA polymerase Zeta (REV3L) US 2011/0003295 A1 Jan. 6, 2011 68
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Rho GDP dissociation 23 LO7916 ------inhibitor (GDI) beta (ARHGDIB) Rho GTPase activating 2 X78817 -- -- protein 4 (ARHGAP4) Rho GTPase activating 1 P98.171 protein 4 (ARHGAP4) (low match) Rho-associated, coiled-coil 1 ABO14519 containing protein kinase 2 (ROCK2) ribonuclease 6 precursor 2 U85625 ------(RNASE6PL) ribonuclease 6 precursor U85625 (RNASE6PL) (low match) ribonuclease, RNase A family, X55.988 -- 2 (liver, eosinophil-derived neurotoxin) (RNASE2) ribonucleasef angiogenin 3 M36717 ------inhibitor (RNH) ribonucleoside diphosphate X65708 reductase M1 subunit ribonucleotide reductase M2 P31350 polypeptide (non-exact 91%) ribophorin I (RPN1) YOO281 ------ribophorin II (RPN2) YOO282 ------ribosomal 18S rRNA 3 M10098 ribosomal 28S RNA M11167 ribosomal phosphoprotein P0, D28418 5'UTR (low match) Ribosomal protein ribosomal protein L10 3 O L25899 ------+ high in many libraries (RPL10) RIBOSOMAL PROTEIN 2 P53O25 L10A (CSA-19) ribosomal protein L11 4 X79234 ------+ Alveolar (RPL11) rhabdomyosarcoma ribosomal protein L12 2 LO6SOS ------(RPL19) ribosomal protein L13 1 P26373 ------+ high in many libraries (PRL13) ribosomal protein L14 4 D87735 ------+ high in many libraries (RPL14) ribosomal protein L17 4 X53777 -- blood only (RPL17) ribosomal protein L18 10 L11566 ------(RPL18) ribosomal protein L183 S LOSO93 ------+ High in fetal adrenal (RPL18A) gland and skin ribosomal protein L183 2 X80821 -- homologue ribosomal protein L19 15 X63527 ------(RPL19) ribosomal protein L21 6 U14967 ------(RPL21) ribosomal protein L22 3 D17652 ------(RPL22) ribosomal protein L23 2 X55954 ------+ high in many libraries (RPL23) ribosomal protein L23a 5 U37230 ------+ high in many libraries (RPL23A) ribosomal protein L26 8 X69392 ------(RPL26) ribosomal protein L27 6 LOSO94 ------(RPL27) ribosomal protein L27a 10 U14968 ------(RPL27A) ribosomal protein L28 6 U14969 ------(RPL28) US 2011/0003295 A1 Jan. 6, 2011 69
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu ribosomal protein L29 6 U10248 ------(RPL29) ribosomal protein L3 (RPL3) 81 ------+ high in many libraries ribosomal protein L3 81 XO6323 homologue ribosomal protein L30 6 X79238 ------+ high in lymphoma (RPL30) ribosomal protein L30 1 X79238 (RPL30) (low score) ribosomal protein L31 10 X15940 ------+ High in alveolar (RPL31) rhabdomyosarcoma ribosomal protein L32 3 XO3342 ------(RPL32) ribosomal protein L33-like 1 AFO47440 ------ribosomal protein L34 S L38941 ------(RPL34) ribosomal protein L34 1 L38941 (RPL34) (low match) ribosomal protein L37 S D23661 ------+ high in barstead (RPL37) OState ribosomal protein L37a 4 X66699 ------+ high in many libraries ribosomal protein L38 1 Z26876 ------+ high in many libraries (PRL38) ribosomal protein L4 (RPL4) 27 D23660 ------+ high in many libraries ribosomal protein L41 4 AFO26844 ------+ high in many libraries (RPL41) ribosomal protein L5 (RPL5) 14 U14966 ------+ High in alveolar rhabdomyosarcoma ribosomal protein L5 (RPL5) 1 U14966 (low match) ribosomal protein L6 (RPL6) 7 X69391 ------+ high in many libraries ribosomal protein L7 (RPL7) 14 XS2967 ------+ high in conorm ribosomal protein L7a 1S M36O72 ------+ High in uterus, and (RPL7A) Seminoma ribosomal protein L8 (RPL8) S Z284O7 ------+ high in ovary ribosomal protein L9 (RPL9) 10 UO9953 ------ribosomal protein S10 5 U14972 ------+ high in many libraries (RPS10) ribosomal protein S11 4 XO6617 ------+ high in many libraries (RPS11) ribosomal protein S11 1 ABOO71S2 (RPS11) (low match) ribosomal protein S12 3 X53505 ------+ high in many libraries (RPS12) ribosomal protein S13 2 LO1124 ------(RPS13) ribosomal protein S14 12 M13934 ------(RPS14) ribosomal protein S15 2 M324OS ------(RPS15) ribosomal protein S16 3 M60854 ------+ High in prostate (RPS16) invasive tumor ribosomal protein S17 2 M13932 ------+ high in many libraries (RPS17) ribosomal protein S18 8 X691SO ribosomal protein S19 7 M81757 ------+ high in many libraries (RPS19) ribosomal protein S2 (RPS2) 4 X172O6 ------+ high in many libraries RIBOSOMAL PROTEINS2 2 P1588O (RPS4) ribosomal protein S20 7 LO6498 ------+ high in many libraries (RPS20) ribosomal protein S21 3 LO4483 ------+ high in CD34+/CD38 (RPS21) hematopoietic cells and skin tumor ribosomal protein S23 3 D14530 ------(RPS23) US 2011/0003295 A1 Jan. 6, 2011 70
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu ribosomal protein S24 7 M31520 ------+ high in uterus (RPS24) ribosomal protein S25 3 M64716 ------+ high in barstead (RPS25) prostate ribosomal protein S26 2 X69654 ------(RPS26) ribosomal protein S27 5 US 7847 ------((metallopainstimulin 1) (RPS27) ribosomal protein S28 3 US8682 ------(RPS28) ribosomal protein S29 2 U14973 ------(RPS29) ribosomal protein S3 (RPS3) 9 X55715 ------+ high in many libraries ribosomal protein S3 (RPS3) 1 U14990 (low match) ribosomal protein S3A 21 Z83334 ------+ high in many libraries (RPS3A) ribosomal protein S3A 1 M77234 (RPS3A) (low score) ribosomal protein S4, X- 9 MS8458 ------+ high in ovary and linked (RPS4X) Synovial sarcoma ribosomal protein S4, Y- 2 MS8459 ------linked (RPS4Y) ribosomal protein S5 (RPS5) 4 U14970 ------+ high in lymphoma RIBOSOMAL PROTEIN S6 1 P10660 (PHOSPHOPROTEIN NP33) ribosomal protein S6 (RPS6) 22 M2002O ------ribosomal protein S6 (RPS6) 1 M77232 (non-exact 86%) ribosomal protein S6 kinase, 3 LO7597 ------90kD, polypeptide 1 ribosomal protein S6 kinase, 1 X85106 90kD, polypeptide 2 ribosomal protein S7 (RPS7) 4 Z25,749 ------ribosomal protein S8 (RPS8) 6 X67247 ------ribosomal protein S9 (RPS9) 8 U14971 colon tumor ribosomal protein, large, PO 18 M1788S T -- -- (RPLPO) ribosomal protein, large, P1 12 M17886 T ------(RPLP1) ribosomal RNA 18S 11 XO32OS (=M10098; KO3432) (=polyadenylating sequence) ribosomal RNA 28S 2 M11167 ribosomal RNA, 16S U25.123 ring finger protein (non-exact AJOO1019 58%) ring finger protein 3 (RNF3) AJOO1019 ring finger protein 4 (RNF4) 3 ABOOO468 ------ring zinc-finger protein 3 U41315 ------
RNA (guanine-7-) ABOO7858 ------methyltransferase (RNMT) RNA binding motif protein 5 4 U23946 ------(RBMS) RNA binding motif, single D28483 ------stranded interacting protein 2 (RBMS2) RNA helicase (putative), X98743 ------(Myc-regulated DEAD box protein) (MRD8) RNA helicase-related protein AFO832SS ------RNA pol II largest subunit 2 X74872 RNA polymerase I subunit AFOO8442 ------(RPA40) US 2011/0003295 A1 Jan. 6, 2011 71
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
RTVP-1 protein 2 X91911 ------S100 calcium-binding protein 2 M81457 ------A10 (annexin II ligand, calpactin I, light polypeptide (p11)) (S100A10) S100 calcium-binding protein 1 X802O1 ------A11 (calgizZarin) (S100A11) S100 calcium-binding protein 3 M80S63 B -- -- A4 (calcium protein, calvasculin, metastasin, murine placental homolog)(S100A4) S100 calcium-binding protein 7 M21 OOS -- -- + high in bone marrow A8 (calgranulin A) (S100A8) S100 calcium-binding protein 14 XO6233 -- -- high in invasive larynx A9 (calgranulin B) (S100A9) Squamous cell carcinoma S164 gene 1 AF109907 S-adenosylmethionine 3 M880O3 ------decarboxylase 1 (AMD1) SB classII histocompatibility 5 M27487 ------antigen alpha-chain SC35-interacting protein 1 5 AFO3O234 ------(SRRP129) scaffold attachment factor B 1 UT2355 ------(SAFB) scaffold attachment factor B 1 UT2355 (SAFB) (non-exact 78%) scRNA molecule, transcribed 1 L13713 from Alu repeat SEC14 (S. cerevisiae)-like 4 D67029 ------(SEC14L) SEC23-like protein B 2 X97O65 ------(SEC23B) SEC63 (SEC63) 1 AF1 OO141 ------Secreted protein, acidic, 7 M25746 ------+ high in bone marrow cysteine-rich (osteonectin) Strona (SPARC) Secretory carrier membrane 1 AFO38966 -- -- protein 1 (SCAMP1) Secretory carrier membrane 1 AFOOSO38 ------protein 2 (SCAMP2) Secretory carrier membrane 1 AFOOSO39 protein 3 (SCAMP3) Secretory granule 1 M33649 proteoglycan core (clones lambda-PG|6,7,8) Selectin L (lymphocyte 43 X17519 ------adhesion molecule 1) (SELL) selectin P ligand (SELPLG) 13 UO2297 -- -- Sema domain, 2 U60800 ------immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D (SEMA4D) SeriArg-related nuclear matrix 4 AFO48977 ------protein (plenty of prolines 101-like) (SRM160) serine palmitoyltransferase 1 YO8685 ------subunit I (SPTI) serine palmitoyltransferase, 1 ABO11098 ------subunit II (LCB2) serine protease 1 JO2907 serine protease inhibitor, 1 UT8095 ------Kunitz type, 2 (SPINT2) serine/threonine kinase 10 1 ABO15718 ------(STK10) US 2011/0003295 A1 Jan. 6, 2011 72
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu serine/threonine kinase 19 1 L26260 ------(STK19) serine/threonine kinase 4 1 U18297 -- -- (STK4) serine/threonine protein 1 X66358 ------kinase KKLALRE (KKIALRE) serine/threonine protein- 1 Y1O256 ------kinase (NIK) SERINETHREONINE- 1 P37023 PROTEINKINASE RECEPTORR3 PRECURSOR (SKR3) Serologically defined colon 2 AFO39694 cancer antigen 16 (NY-CO 16) Serologically defined colon 1 AFO39698 B, T ------cancer antigen 33 (SDCCAG33) Serologically defined colon 1 AFO39698 cancer antigen 33 (SDCCAG33) (low score) Serologically defined colon 1 AFO39698 cancer antigen 33 (SDCCAG33) (low score) serum deprivation response 1 AFO85481.1 (phosphatidylserine-binding protein) (SDPR) (=S67386) serum glucocorticoi 2 Y1OO32 ------regulated kinase (SGK) SET domain, bifurcated 1 2 D31891 ------(SETDB1) SH2 domain protein 1A, 1 AFO73019 T -- Duncan's disease lymphoproliferative syndrome) (SH2D1A) SH3 binding protein (SAB) 2 ABOOSO47 ------SH3 domain protein 1B 4 U61167 ------(SH3D1B) SH3BGR PROTEIN (-21- 1 P55822 GLUTAMIC ACID-RICH PROTEIN; 21-GARP) (non exact 82% aa) SH3-binding domain glutamic 1 AFO42O81 ------acid-rich protein like
SH3-domain GRB2-like 1 1 U65999 ------(SH3GL1) SHC (Src homology 2 2 X68148 ------domain-containing) transforming protein 1 (SHC1) siah binding protein 1 2 US 1586 ------(SiahBP1) siah binding protein 1 1 US 1586 (SiahBP1) (non-exact, 69%) Sialomucin CD164 (CD164) 9 D14043 sialophorin (gpL115, 2 JO4536 leukosialin, CD43) (SNP) sialyltransferase (STHM) 1 U145SO ------sialyltransferase 1 (beta- 2 X17247 ------galactoside alpha-2,6- sialytransferase) (SIAT1) sialyltransferase 4A (beta- 1 AFOS9321 B ------galactosidase alpha-2,3- sialytransferase) (SIAT4A) sialyltransferase 8 (alpha-2,8- 1 L41680 -- polysialytransferase) D (SIAT8D) US 2011/0003295 A1 Jan. 6, 2011 73
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu signal peptidase 25kDa. 1 L389SO Subunit signal recognition particle 1 X73459 ------14 kD (homologous Alu RNA binding protein) (SRP14) signal recognition particle 1 US 1920 ------54 kD (SRP54) signal recognition particle 2 U20998 ------9 kD (SRP9) signal recognition particle 5 XO6272 receptor (docking protein) SRPR signal regulatory protein, beta, 5 Y10376 -- -- 1 (SIRP-BETA-1) signal sequence receptor, 2 Z12830 -- -- alpha (translocon-associated protein alpha) (SSR1) signal sequence receptor, beta 2 X74104 ------(translocon-associated protein beta) (SSR2) signal transducer and activator 4 L41142 ------of transcription (STAT5A) signal transducer and activator 1 U18671 -- of transcription 2, 113 KD (STAT2) signal transducer and activator 3 L29277 of transcription 3 (acute-phase response factor) (STAT3) signal transducer and activator 2 U4873O ------of transcription 5A (STAT5A) signal transducing adaptor U43899 molecule (SH3 domain and ITAM motif) 1 (STAM) silencing mediator of retinoid U37146 and thyroid hormone action (SMRT) similar to beta-transducin UO2609 ------Superfamily proteins (SAZD) similar to S. cerevisiae SSM4 ABO11169 ------(TEB4) similar to yeast pre-mRNA AFO26031 ------splicing factors, Prp1 Zer1 and Prp6 SIT protein AJO10059.1 Sjogren syndrome antigen A1 2 M62800 -- (52 kD, ribonucleoprotein autoantigen SS-A/Ro) (SSA1) Sjogren syndrome antigen A1 M628OO (52 kD, ribonucleoprotein autoantigen SS-A/Ro) (SSA1) (non-exact 63%) (match to Zinc finger) SKAP55 homologue (SKAP- 1 AJOO4886 ------HOM) skb1 (S. pombe) homolog 2 AFO15913 ------(SKB1) skeletal muscle abundant 1 X87613 ------protein SMA3 (SMA3) 1 X833OO ------Small acidic protein 3 U51678 ------Small EDRK-rich factor 2 2 Y10351 ------+ high in fetal lung (SERF2) Small inducible cytokine A5 2 M21121 ------+ high in many libraries (RANTES) (SCYA5) Small inducible cytokine 1 D63789 Subfamily C, member 2 (SCYC2) US 2011/0003295 A1 Jan. 6, 2011 74
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Small nuclear 2 M15841 ------ribonucleoprotein polypeptide B" (SNRPB2) Small nuclear 4 JO4615 ------ribonucleoprotein polypeptide N (SNRPN) Small nuclear 2 JO4564 ------ribonucleoprotein polypeptides B and B1 (SNRPB) Small nuclear RNA activating 1 AFO93593 ------complex, polypeptide 5, 19 kD (SNAPC5) Smallest Subunit of ubiquinol- 1 DSS636 ------+ high in fetal lung cytochrome c reductase SMC (mouse) homolog, X 1 L2S270 ------chromosome (SMCX) SMT3B protein (2) 2 X99585 ------SNARE protein (YKT6) (low 1 U95735 match) SNC19 1 U20428 SNC73 protein (SNC73) 2 JOO220 ------+ high in many libraries solute carrier family 1 (neutral 2 U53347 ------amino acid transporter), member 5 (SLC1A5) Solute carrier family 11 7 DSO403 -- (proton-coupled divalent metal ion transporters), member 1 (SLC11A1) solute carrier family 17 1 U90545 -- (sodium phosphate), member 3 (SLC17A3) solute carrier family 19 (folate 1 U17566 B, lymphoma -- -- transporter), member 1 (SLC19A1) solute carrier family 2 1 KO3195 ------(facilitated glucose transporter), member 1 (SLC2A1) solute carrier family 23 3 D87075 ------(nucleobase transporters), member 2 (SLC23A2) solute carrier family 25 1 AFO70548 B, T ------(mitochondrial carrier; oxoglutarate carrier), member 11 (SLC25A11) solute carrier family 31 3 U.83461 -- -- (copper transporters), member 2 (SLC31A2) Solute carrier family 4, anion 1 X621.37 ------exchanger, member 2 (erythrocyte membrane protein band 3-like 1) Solute carrier family 4, sodium 1 ABO18282 -- bicarbonate cotransporter, member 8 (SLC4A8) solute carrier family 7 2 M8O244 T, W ------(cationic amino acid transporter, y+ system), member 5 (SLC7A5) solute carrier family 7 3 D87432 ------(cationic amino acid transporter, y+ system), member 6 (SLC7A6) US 2011/0003295 A1 Jan. 6, 2011 75
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu solute carrier family 7 1 D87432 (cationic amino acid transporter, y+ system), member 6 (SLC7A6) (non exact 77%) solute carrier family 9 1 AFO3O409 ------(sodium hydrogen exchanger), isoform 6 (SLC9A6) somatic cytochrome c (HCS) 2 M22877 SON DNA binding protein 2 X63753 ------(SON) son of sevenless (Drosophila) 1 L13858 ------homolog 1 (SOS1) sorcin (SRI) 1 M32886 sortilin 1 (SORT1) 2 X98248 ------sortilin-related receptor, 6 YO8110 L(DLR class) A repeats containing (SORL1) sorting nexin 1 (SNX1) 3 U53225 ------sorting nexin 2 (SNX2) 2 AFO43453 sorting nexin 6 (SNX6) 1 AF121856.1 (=U83194.1 TRAF4 associated factor 2) Sp3 transcription factor (SP3) 1 X68560 ------Sp3 transcription factor (SP3) 4 M97191 ------special AT-rich sequence 1 M97287 binding protein 1 (binds to nuclear matrix scaffold associating DNAs) (SATB1) speckle-type POZ protein 4 AJOOO644 (SPOP) speckle-type POZ protein 1 AJOOO644 (SPOP) (non-exact) spectrin SH3 domain binding 6 U87166 ------protein 1 (SSH3BP1) Spectrin, alpha, non- 2 JOS243 ------erythrocytic 1 (alpha-fodrin) (SPTAN1) spermidine?spermine N1- 11 M55580 acetyltransferase (SAT) spermidine?spermine N1- 1 U40369 acetyltransferase (SAT) (non exact, 84%) spermine synthase (SMS) 1 ADOO1528 ------SPF31 (SPF31) 1 AFO83190 ------sphingomyelin 1 X52679 ------phosphodiesterase 1, acid lysosomal (acid sphingomyelinase) (SMPD1) SPINDLINEHOMOLOG 1 Q99865 (PROTEIN DXF34) Spinocerebellar ataxia 1 3 X792.04 B -- -- (olivopontocerebellar ataxia 1, autosomal dominant, ataxin 1) (SCA1) Spinocerebellar ataxia 2 1 UTO323 B -- (olivopontocerebellar ataxia 2, autosomal dominant, ataxin 2) (SCA2) spinocerebellar ataxia 7 2 AJOOOS17 -- (olivopontocerebellaratrophy with retinal degeneration) (SCA7) Spliceosome associated 3 U41371 ------protein (SAP 145) splicing factor (CC1.3) 2 L10910 ------(CC1.3) splicing factor SRp40-1 7 U3O826 ------(SRp40) US 2011/0003295 A1 Jan. 6, 2011 76
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu splicing factor, 3 M740O2 B ------arginine serine-rich 11 (SFRS11) splicing factor, 4 L41887 ------arginine?serine-rich 7 (35 kD) (SFRS7) Src-like adapter protein (non- U3O473 exact, 76% aa) Src-like-adapter (SLA) 6 D89077 ------Src-like-adapter (SLA) (low D89077 match) Src-like-adapter (SLA) (low U44403 score) stannin (SNN) 2 AFO3O196 ------STAT induced STAT ABOO4904 -- inhibitor 3 (SSI-3) STE20-like kinase 3 (MST-3) 2 AFO24636 ------step II splicing factor SLU7 AF101.074 ------(SLU7) steroid sulfatase M17591 steroid sulfatase (microsomal), JO4964 ------arylsulfatase C, isozyme S (STS) sterol carrier protein 2 (SCP2) MSS421 ------sterol O-acyltransferase (acyl- AFOS92O2 -- Coenzyme A: cholesterol acyltransferase) 1 (SOAT1) stimulated trans-acting factor 6 X82200 ------(50 kDa) (STAF50) Striatin, calmodulin-binding U17989 protein (STRN) (low match, 71% aa) Stromal antigen 2 (STAG2) 2 Z75331 ------stromal interaction molecule 1 3 US2426 ------(STIM1) structure specific recognition 1 M86737 ------protein 1 (SSRP1) Succinate dehydrogenase S L21936 -- complex, Subunit A, flavoprotein (Fp) (SDHA) Succinate dehydrogenase 1 U17248 ------complex, Subunit B, iron sulfur (Ip) (SDHB) Succinate dehydrogenase 1 US 7877 ------complex, Subunit C, integral membrane protein, 15 kD (SDHC) Succinate dehydrogenase 3 ABOO62O2 ------complex, Subunit D, Integral membrane protein (SDHD) Succinate-CoA ligase, GDP- 1 AFOS8954 ------forming, beta Subunit (SUCLG2) Succinyl CoA synthetase 1 Z68204 SudD (suppressor of bimD6, 2 AFO13591 ------Aspergilius nidians) homolog (SUDD) Sulfotransferase family 1A, 1 L19999 ------phenol-preferring, member 1 (SULT1A1) Sulfotransferase family 1A, 1 U376.86 phenol-preferring, member 3 (SULT1A3) (non-exact 67%) Superoxide dismutase 1, 4 XO2317 ------Soluble (amyotrophic lateral sclerosis 1 (adult)) (SOD1) Superoxide dismutase 2, 5 YOO985 ------mitochondrial (SOD2) US 2011/0003295 A1 Jan. 6, 2011 77
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Supervillin (SVIL) 2 AFOS1851 ------Suppression of tumorigenicity 2 U15131 -- -- 5 (ST5) Suppression of tumorigenicity 1 U15779 5 (STS) (non-exact 82%) Suppressor of K+ transport 1 AFO38960 defect 1 (SKD1) Suppressor of Ty 1 AFO64804 (S. cerevisiae) 3 homolog (SUPT3H) Suppressor of Ty 2 U38817 -- (S. cerevisiae) 4 homolog 1 (SUPT4H1) Suppressor of Ty 2 US 64O2 (S. cerevisiae) 5 homolog (SUPTSH) Suppressor of Ty 2 U46691 -- (S. cerevisiae) 6 homolog (SUPT6H) Suppressor of variegation 3-9 1 AFO19968 (Drosophila) homolog 1 (SUV39H1) Survival of motor neuron 1, 1 U18423 telomeric (SMN1) SWI/SNF related, matrix 1 M881 63 associated, actin dependent regulator of chromatin, Subfamily a, member 1 (SMARCA1) (non-exact, 75%) SWI/SNF related, matrix 2 D2615S associated, actin dependent regulator of chromatin, Subfamily a, member 2 (SMARCA2) SWI/SNF related, matrix 1 D261.56 -- associated, actin dependent regulator of chromatin, Subfamily a member 4 (SMARCA4) SWI/SNF related, matrix 4 U66616 -- associated, actin dependent regulator of chromatin, Subfamily c, member 2 (SMARCC2) SWI/SNF related, matrix 2 AFO35262 B, W associated, actin dependent regulator of chromatin, Subfamily e, member 1 (SMARCE1) synaptobrevin-like 1 (SYBL1) 1 X958O3 synaptosomal-associated AJO11915 protein, 23 kD (SNAP23) Syndecan binding protein 15 AFOO6636 -- (syntenin) (SDCBP) synovial sarcoma, translocated 2 X792O1 to X chromosome (SSXT) Syntaxin 16 AFO38.897 Syntaxin 3A (STX3A) U32315 Syntaxin 6 (STX6) AJOO2O78.1 SYNTAXIN BINDING OOO186 PROTEIN3 (UNC-18 HOMOLOG3) (UNC-18C) Syntaxin-16C AFOO8937 SYT interacting protein (SIP) AFO80S61 T cell activation, increased 4 M88.282 late expression (TACTILE) US 2011/0003295 A1 Jan. 6, 2011 78
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu T cell receptor Valpha gene 2 XS8744 segmentV-alpha-7 (clone IGRa11) T cell receptor Valpha gene 1 X5874O segmentV-alpha-w27 T3 receptor-associating S S83390 ------cofactor-1 tafazzin (cardiomyopathy, 1 X92763 ------dilated 3A (X-linked): endocardial fibroelastosis 2: Barth syndrome) (TAZ) TAFII100 protein (non-exact 1 U8O191 53%) tankyrase, TRF1-interacting 1 AFO82556 ------ankyrin-related ADP-ribose polymerase (TNKS) TAP1, TAP2, LMP2, LMP7 1 X664O1 and DOB TAR DNA-binding protein-43 6 U23731 ------Tat interactive protein (60 kD) 2 U4O989 ------(TIP60) TATA box binding protein 1 OOO268 (TBP)-associated factor, RNA polymerase II, C1, 130 kD (TAF2C1) (non-exact, 55%) TATA box binding protein 4 X97999 ------(TBP)-associated factor, RNA polymerase II, F, 55 kD (TAF2F) TATA box binding protein 2 U21858 ------(TBP)-associated factor, RNA polymerase II, G, 32 kD (TAF2G) TATA box binding protein D63705 ------(TBP)-associated factor, RNA polymerase II, I, 28 kD (TAF2I) Tax1 (human T-cell leukemia U33821 ------virus type I) binding protein 1 (TAX1BP1) T-box 2 (TBX2) (non-exact U28049 ------77%) TBP-associated factor 172 AJOO1017 ------TAF-172) T-cell death-associated gene 8 U95218 -- TDAG8) T-cell leukemia/lymphoma 1A X82240 -- TCL1A) T-cell leukemia/lymphoma 1A X82240 TCL1A) (low match) -cell receptor (delta D2-J1- M22197 egion) (clone K3B) T-cell receptor (V beta 5.1, J M97705 beta 1.5, C beta1) (low match) T-cell receptor alpha delta 2 AEOOO662 (=M94081) T-cell receptor alpha 1 B3962S enhancer-binding protein, short form (=X58636 Mouse LEF1 lymphoid enhancer binding factor 1 (=D16503)) T-cell receptor delta gene D2- 1 M22197 J1-region, clone K3B T-cell receptor germline beta 1 M11955 chain gene V-region (V)V- beta-MT1-1 US 2011/0003295 A1 Jan. 6, 2011 79
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu T-cell receptor germline beta- 1 M14159 -- only in blood chain gene J2.1 exon T-cell receptor germline delta- 2 M221S2 chain D-J region T-cell receptor interacting 2 AJ224878 -- molecule (TRIM) protein T-cell receptor rearranged 1 M21784 elta-chain, V-region (V-delta 3-J) T-cell receptor, alpha 3 AEOOO660 ------(V, D, J, C) (TCRA) T-cell receptor, beta cluster 3 L34740 ------+ high in pancreas (TCRB) T-cell receptor, delta 2 X73617 ------(V, D, J, C) (TCRD) T-cell, immune regulator 1 3 U4528S only found in tumor (TCIRG1) TCF-1 mRNA for T cell factor 1 1 X59870 TCF-1 mRNA for T cell factor 1 X59870 (splice form B) (low match) T-COMPLEX PROTEIN 1, 1 Q99832
A SUBUNIT (TCP-1- A) (CCT-ETA) (HIV-1 NEF INTERACTING PROTEIN) T-COMPLEX PROTEIN 1, 1 P50990 THETA SUBUNIT (TCP-1- THETA) (CCTTHETA) (KIAAO002) TCR eta = T cell receptor(eta- 1 S94421 exon) TCRW Beta 13.2 1 X75419 TERA 1 ACOO4472 estis enhanced gene transcript 33 X75861 ------(TEGT) etracycline transporter-like 2 L11669 ------protein (TETRAN) etratricopeptide repeat 1 U46570 ------domain 1 (TTC1) etratricopeptide repeat 1 U46571 ------domain 2 (TTC2) etratricopeptide repeat 1 D84296 ------domain 3 (TTC3) TGFB1-induced anti- 1 D86970 ------apoptotic factor 1 (TIAF1) hioredoxin reductase 1 3 S79851 ------(TXNRD1) THIOREDOXIN- 1 P3OO48 DEPENDENT PEROXIDE REDUCTASE PRECURSOR, mitochondrial (ANTI OXIDANT PROTEIN 1) (AOP-1) hreonyl-tRNA synthetase 1 M6318O ------(TARS) hrombin inhibitor 1 Z22658 hrombospondin 1 (THBS1) 2 XO4665 ------hromboxane A synthase 1 1 M80647 ------(platelet, cytochrome P450, subfamily V) (TBXAZ1) hymidine kinase 2, 2 X76104 ------mitochondrial (TK2) hymidylate kinase (CDC8) 1 L16991 ------hymine-DNA glycosylase 2 US 1166 ------(TDG) Thymosin, beta 10 (TMSB10) 2 M2O259 ------hymosin, beta 4, X 29 M17733 ------chromosome (TMSB4X) US 2011/0003295 A1 Jan. 6, 2011 80
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu hyroid autoantigen 70 kD (Ku 7 JO4611 antigen) (G22P1) hyroid hormone receptor 1 AFO16270 -- -- coactivating protein (SMAP) hyroid hormone receptor 2 L40357 ------interactor 7 (TRIP7) hyroid hormone receptor 4 L40411 interactor 8r (TRIP8) hyroid hormone receptor 1 D83.783 associated protein, 230 kDa subunit (TRAP230) hyroid receptor interacting 2 L40388 -- -- protein 15 (TRIP15) TI-227H 1 D50525 TIA1 cytotoxic granule 1 M77142 ------associated RNA-binding protein (TIA1) issue inhibitor of 1 XO2598 metalloproteinase 1 (erythroid potentiating activity, collagenase inhibitor) (TIMP1) issue inhibitor of M32304 ------hig h in placenta metalloproteinase 2 (TIMP2) issue specific transplantation US8766 ------antigen P35B (TSTA3) itin (TTN) X64697 ------hig h in muscle TNF receptor-associated U12597 ------actor 2 (TRAF2) TNF receptor-associated AF1109081 actor 3 (TRAF3) TNF receptor-associated U78798 actor 6 (TRAF6) (low match) ol-like receptor 1 (TLR1) U88540 -- ol-like receptor 2 (TLR2) U88878 -- -- ol-like receptor 4 (TLR4) U8888O -- ol-like receptor 5 (TILR5) AFOS1151 -- opoisomerase (DNA) I O32SO -- -- (TOP1) opoisomerase (DNA) II beta 2 X68060 ------(180 kD) (TOP2B) opoisomerase (DNA) III beta 3 D87012 (TOP3B) TR3beta 1 D85245 TRAF family member 3 U63830 : associated NF-kB activator (TANK) TRANSALDOLASE 1 P37837 transaldolase 1 (TALDO1) 4 L19437 transaldolase-related protein 1 AFO10398 transcobalamin II (TCII) 1 AFO47576 transcription elongation factor 2 Z47087 B (SIII), polypeptide 1-like (TCEB1L) transcription elongation factor 1 L47345 B (SIII), polypeptide 3 (110 kD, elongin A) (TCEB3) transcription factor 12 (HTF4, 1 M83233 ------helix-loop-helix transcription actors 4) (TCF12) transcription factor 17 2 D89928 -- (TCF17) transcription factor 4 (TCR4) 2 X52079 ------transcription factor 6-like 1 2 M62810 : -- -- (mitochondrial transcription actor 1-like) (TCF6L1) transcription factor 7-like 2 1 Y11306 ------(T-cell specific, HMG-box) (TCF7L2) US 2011/0003295 A1 Jan. 6, 2011 81
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. O Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li transcription factor binding to X96717 ------GHM enhancer 3 (TFE3 transcription factor IL-4 Stat AFO67575 ------transcription factor IL-4 Stat U16031 (low match) transcription factor ISGF-3 M97935 (=M97936) transcription factor REST AS6138 transcription factor TFIID Z22828 transcriptional adaptor 2 AFO64094 (ADA2, yeast, homolog)-like (TADA2L) transcriptional intermediary AFOO9353 actor 1 (TIF1) (non-exact 72%) transducin (beta)-like 1 Y12781 ------(TBL1) transducin-like enhancer of M994.38 -- -- split 3, homolog of Drosophila E(sp1) (TLE3) Transformation transcription AFO76974 ------domain-associated protein (TRRAP) transformation-sensitive, M86752 -- -- similar to Saccharomyces cerevisiae STI1 (STI1L) transforming growth factor ABOO9356 beta-activated kinase 1 (TAK1) (non-exact 78%) transforming growth factor AJ222700 ------beta-stimulated protein TSC 22 (TSC22) transforming growth factor, LO7594 -- -- beta receptor III (betaglycan, 300 kD) (TGFBR3) transforming growth factor, 4507466 ------beta-induced, 68 kD (TGFBI) TRANSFORMING Q15582 GROWTH FACTOR-BETA NDUCED PROTEINIG-H3 PRECURSOR (BETA IG-H3) transforming, acidic coiled AFO4991O coil containing protein 1 (TACC1) (non-exact 70%) transgelin 2 (TAGLN2) D21261 ------transgelin 2 (TAGLN2) (non D21261 exact) trans-Golgi network protein AFO29316 -- (46,48, 51 kD isoforms) (TGN51) transient receptor potential X89066 -- -- channel 1 (TRPC1) transketolase (Wernicke L12711 -- -- Korsakoff syndrome) (TKT) translation factor Sui1 AFO 646O7 -- -- homolog (GC20) translin (TSN) X78627 ------translin-associated factor X X95073 -- -- (TSNAX) transmembrane glycoprotein U79725 (A33) transmembrane protein X6991O ------(63 kD), endoplasmic reticulum Golgi intermediate compartment (P63) transmembrane protein 1 ABOO1523 -- (TMEM2) US 2011/0003295 A1 Jan. 6, 2011 82
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
TRANSMEMBRANE 1 P51805 PROTEINSEX PRECURSOR (non-exact 65%) transmembrane trafficking 2 X97442 ------protein (TMP21) transporter 1, ABC (ATP 3 L21208 ------binding cassette) (TAP1) Treacher Collins- 2 U40847 ------+ high in many libraries Franceschetti syndrome 1 (TCOF1) triosephosphate isomerase 1 2 X69723 ------(TPI1) tropomyosin 2 XO42O1 ------tropomyosin 4 (TPM4) 2 XO5276 ------TRPM-2 protein 2 M63376 tryptase I precursor (non-exact A35863 64%)(=P20231) tryptophan rich basic protein Y12478 (WRB) tryptophanyl-tRNA synthetase XS9892 ------(WARS) Ts translation elongation L37936 ------actor, mitochondrial (TSFM) topoisomerase (DNA) II beta Z15115 ------(180 kD) Tu translation elongation 4 L3899S actor, mitochondrial (TUFM) tuberous sclerosis 1 (TSC1) AFO131.68 ------tuberous sclerosis 2 (TSC2) X75621 ------tubulin, alpha 1 (testis XO6956 -- -- specific) (TUBA1) tubulin, alpha, ubiquitous (K- 11 KOOSS8 ------+ high in many libraries ALPHA-1) tubulin, alpha, ubiquitous (K- KOOSS8 ALPHA-1) (low match) tubulin-specific chaperone c U61234 ------(TBCC) tumor necrosis factor (ligand) 7 U37518 ------Superfamily, member 10 (TNFSF10) tumor necrosis factor (ligand) AFO46888 ------Superfamily, member 13 (TNFSF13) tumor necrosis factor (ligand) AFO36581 Superfamily, member 14 (TNFSF14) tumor necrosis factor (ligand) D38122 -- Found only in library Superfamily, member 6 386: T-cell lymphoma (TNFSF6) tumor necrosis factor (ligand) LO9753 B only Superfamily, member 8 (TNFSF8) tumor necrosis factor alpha- AFO 61034 ------inducible cellular protein containing leucine Zipper domains (FIP2) Tumor necrosis factor 2 M63928 -- -- receptor Superfamily member 7 (TNFRSF7) tumor necrosis factor receptor 1 AFO16266 ------Superfamily, member 10b (TNFRSF10B) tumor necrosis factor receptor 3 AFO12629 -- Superfamily, member 10c, decoy without an intracellular domain (TNFRSF10C) US 2011/0003295 A1 Jan. 6, 2011 83
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu tumor necrosis factor receptor 1 AFO23849 found only in prostate Superfamily, member 10d, decoy with truncated death domain (TNFRSF1OD) (non exact 84%) tumor necrosis factor receptor 1 U945.08 ------Superfamily, member 12 (translocating chain association membrane protein) (TNFRSF12) tumor necrosis factor receptor 1 UTO321 ------Superfamily, member 14 (herpesvirus entry mediator) (TNFRSF14) tumor necrosis factor receptor 5 US 21.65 ------Superfamily, member 1B (TNFRSF1B) tumor necrosis factor receptor 1 X63717 B, W -- Superfamily, member 6 (TNFRSF6) tumor necrosis factor receptor 1 M63928 -- -- Superfamily, member 7 (TNFRSF7) tumor necrosis factor, alpha- 8 M92357 ------induced protein 2 (TNFAIP2) tumor necrosis factor, alpha- 2 M59465 induced protein 3 (TNFAIP3) tumor protein 53-binding 1 AFO78776 ------protein, 1 (TP53BP1) tumor protein p53 (Li- 1 M14695 ------Fraumeni syndrome) (TP53) Tumor protein p53-binding 1 U82939 ------protein (TP53BPL) tumor protein, translationally- 3S X16064 controlled 1 (TPT1) tumor protein, translationally- 1 X16064 controlled 1 (TPT1) (low score) tumor rejection antigen (gp96) 9 X15187 ------(TRA1) tumorous imaginal discs 2 AFO61749 -- (Drosophila) homolog (TID1) TXK tyrosine kinase (TXK) 2 L27071 type II integral membrane 1 AJOO1685 -- found only in fetal protein (NKG2-E) liverispleen TYRO protein tyrosine kinase 3 AFO19562 -- binding protein (TYROBP) tyrosine 3- 1 X57346 ------+ high in ecnorm monooxygenase/tryptophan 5 monooxygenase activation protein, beta polypeptide (YWHAB) tyrosine 3- 1 M86400 monooxygenase/tryptophan 5 monooxygenase activation protein, Zeta polypeptide (YWHAZ) tyrosine 3- 1 M86400 monooxygenase/tryptophan 5 monooxygenase activation protein, Zeta polypeptide (YWHAZ) Tyrosine kinase 2 (TYK2) 3 XS4637 ------TYROSINE-PROTEIN 2 P43403 KINASEZAP-70 (70 KD ZETA-ASSOCIATED PROTEIN) (SYK-RELATED TYROSINE KINASE) US 2011/0003295 A1 Jan. 6, 2011 84
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu tyrosyl-tRNA synthetase 1 U89436 ------(YARS) O1 small nuclear RNA 1 M14387 U19H snoRNA (=M63485 1 AJ224166 R. norvegicus matrin 3) U2(RNU2) Small nuclear 1 M96982 ------RNA auxillary factor 1 (non standard symbol) (U2AF1) U22 snoRNA host gene 2 U4058O (UHG) O4/U6-associated RNA 4 AFO16370 ------splicing factor (HPRP3P) O49 small nuclear RNA 1 X96649 U5 SnRNP-specific protein 1 ABOO7510 ------(220 kD), ortholog of S. cerevisiae Prp8p (PRP8) U5 SnRNP-specific protein, 4 D21163 ------16 kD (U5-116 KD) U5 SnRNP-specific protein, 3 Z70200 200 kDa (DEXH RNA helicase family) (U5-200-KD) Uba80 mRNA for ubiquitin 4 S79522 ------+ high in ovary ubiquinol-cytochrome c 1 DSS636 ------+ high in fetal lung reductase (6.4 kD) subunit (UQCR) UBIQUINOL- 1 P47985 CYTOCHROMEC REDUCTASE IRON SULFUR SUBUNIT PRECURSOR (RIESKE RON-SULFUR PROTEIN) (RISP) (low match) ubiquitin A-52 residue 2 XS 6999 ribosomal protein fusion product 1 (UBA52) ubiquitin activating enzyme 1 AFO94516 ------E1-like protein (GSA7) ubiquitin C (UBC) S ABOO9010 ------+ high in ovary ubiquitin carboxyl-terminal 1 M3O496 ------esterase L3 (ubiquitin hiolesterase) (UCHL3) ubiquitin fusion degradation 1 U64444 ------like (UFD1L) ubiquitin protein ligase E3A 1 U84404 B ------(human papilloma virus E6 associated protein, Angelman syndrome) (UBE3A) ubiquitin specific protease 10 4 D80012 ------(USP10) ubiquitin specific protease 11 1 U44839 ------(USP11) ubiquitin specific protease 15 3 ABO11101 ------(USP15) ubiquitin specific protease 19 1 ABO2O698 -- (USP19) ubiquitin Specific protease 4 1 AFO1730S B ------(proto-oncogene) (USP4) ubiquitin Specific protease 4 1 AFO17306 (proto-oncogene) (USP4) (non-exact, 66%) ubiquitin specific protease 7 1 Z724.99 ------(herpesvirus-associated) (USP7) ubiquitin specific protease 8 5 D29956 ------(USP8) UBIQUITIN-ACTIVATING 1 P22314 ENZYMEE1 (A1S9 PROTEIN) (56%) US 2011/0003295 A1 Jan. 6, 2011 85
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu ubiquitin-activating enzyme 1 MS8028 ------E1 (A1S9T and BNT5 emperature sensitivity complementing) (UBE 1) ubiquitin-activating enzyme 1 L341.70 ------E1, like (UBE1L) UBIQUITIN-BINDING 1 U41806 -- -- PROTEIN P62; phosphotyrosine independent igand for the Lck SH2 domain p62 (P62) ubiquitin-conjugating enzyme 2 U49278 ------E2 variant 1 (UBE2V1) ubiquitin-conjugating enzyme X98091 E2 variant 2 (UBE2V2) UBIQUITIN- Q16781 CONUGATING ENZYME E2-17 KD (UBIQUITIN PROTEIN LIGASE) biquitin-conjugating enzyme M74525 ------B (RAD6 homolog) BE2B) uitin-conjugating enzyme AFO32456 ------2G 2 (homologous to yeast UBC7) (UBE2G2) ubiquitin-conjugating enzyme Z29328 ------E2H (homologous to yeast UBC8) (UBE2H) biquitin-conjugating enzyme X92962 ------2L 1 (UBE2IL1) biquitin-conjugating enzyme 3 AJOOOS 19 ------2L 3 (UBE2IL3) biquitin-conjugating enzyme 4 AFO31141 ------2L 6 (UBE2IL6) biquitin-like 1 (Sentrin) 2 U61397 ------(UBL1) UDP-N-acetyl-alpha-D- 2 X85O19 galactosamine:polypeptide N acetylgalactosaminyltransferase 2 (GalNAc-T2) (GALNT2) UDP-N-acetyl-alpha-D- 1 X92689 galactosamine:polypeptide N acetylgalactosaminyltransferase 3 (GalNAc-T3) (GALNT3) (non-exact 65%) unactive progesterone 2 L24804 ------receptor, 23 Kod (P23) unconventional myosin-ID 3 US 7053 uncoupling protein homolog 1 U94592 (UCPH) uncoupling protein homolog 1 U94592 (UCPH) (low match 67%) Unknown gene product 1 ACOO2310 unknown mRNA (clone 1 AFO70542 24514) unknown protein (clone 2 Z70223 ICRFp507L0677) unknown protein (HS.93832) 1 AFO70626 ------unknown protein IT14 1 AFO4O966 uppressor of Ty (S. cerevisiae) 1 D79984 ------6 homolog upregulated by 1,25- 74 ST3591 ------+ high in heart dihydroxyvitamin D-3 (VDUP1) upregulated by 1,25- 1 S73591 dihydroxyvitamin D-3 (VDUP1) (low match) US 2011/0003295 A1 Jan. 6, 2011 86
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu upregulated by 1,25- 1 S73591 dihydroxyvitamin D-3 (VDUP1) (low match) upregulated by 1,25- 1 S73591 dihydroxyvitamin D-3 (VDUP1) (low score) upstream binding factor 1 XS3461 ------(hUBF) UV radiation resistance 2 X990SO ------associated gene (UVRAG) vacuolar proton-ATPase, 4 X71490 ------subunit D: V-ATPase, subunit D (ATP6DV) v-akt murine thymoma viral 1 M631.67 ------oncogene homolog 1 (AKT1) Vanin 2 (VNN2) 3 A132100 vasodilator-stimulated 3 Z46389 ------phosphoprotein (VASP) vav 1 oncogene (VAV1) 1 MS9834 -- vav 2 oncogene (VAV2) 1 S76992 -- -- v-crkavian sarcoma virus 1 D10656 W ------CT10 oncogene homolog (CRK) v-erb-b2 avian erythroblastic 1 M29366 -- eukemia viral oncogene homolog3 (ERBB3) VERSICAN CORE 1 P13611 PROTEIN PRECURSOR Vesicle-associated membrane 1 M361.96 ------protein 1 (synaptobrevin 1) (VAMP1) vesicle-associated membrane 1 U64520 protein 3 (cellubrevin) (VAMP3) v-fos FBJ murine 26 KOO6SO ------+ high in aorta osteosarcoma viral oncogene homolog (FOS) v-fos FBJ murine 1 KOO6SO osteosarcoma viral oncogene homolog (FOS) (low match) villin 2 (eZrin) (VIL2) 1 X51521 ------villin-like protein 1 D88154 vimentin (VIM) 12 XS6134 ------+ high in many libraries vinculin (VCL) 4 M333O8 ------vitamin A responsive; 6 AFO70523 ------cytoskeleton related (JWA) v-jun avian sarcoma virus 17 2 U65928 ------oncogene homolog (JUN) v-mybavian myeloblastosis 1 M15024 -- -- viral oncogene homolog (MYB) voltage-dependent anion 1 LO6132 ------channel 1 (VDAC1) voltage-dependent anion 4 U90943 ------channel 3 (VDAC3) von Hippel-Lindau syndrome 1 L15409 ------(VHL) von Willebrand factor (v WF) 1 XO6828 (low matched) v-raf murine sarcoma 3611 2 L24038 ------viral oncogene homolog 1 (ARAF1) v-raf-1 murine leukemia viral 1 XO3484 ------oncogene homolog 1 (RAF1) v-ral simian leukemia viral 3 M3S416 oncogene homolog B (ras related; GTP binding protein) (RALB) US 2011/0003295 A1 Jan. 6, 2011 87
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
V-relavian 1 L19067 ------reticuloendotheliosis viral oncogene homolog A (nuclear factor ofkappa light polypeptide gene enhancer in B-cells 3 (p65)) (RELA) v-yes-1 Yamaguchi sarcoma 2 M16038 ------viral related oncogene homolog (LYN) WD repeat domain 1 (WDR1) 1 ABO10427 ------WDR1 (=AF020260) 1 AFO2OOS6 WD-repeat protein (HAN11) 2 U94747 ------Williams-Beuren syndrome 12 AFO4SSSS ------chromosome region 1 (WBSCR1) Wiskott-Aldrich syndrome 4 X86019 ------protein interacting protein (WASPIP) X (inactive)-specific transcript 2 M971.68 (XIST) Xeroderma pigmentosum, 3 D21089 ------complementation group C (XPC) XIAP associated factor-1 2 X99699 -- XIB 1 X90392 ------X-linked anhidroitic 1 AFOO3528 ectodermal dysplasia X-ray repair complementing 1 M30938 ------+ high in spleen defective repair in Chinese hamster cells 5 (double strand-break rejoining: Ku autoantigen, 80 kD) (XRCC5) XRP2 protein AJOO7590 yeloid differentiation primary U844.08 ------response gene (88) (MYD88) Zeta-chain (TCR) associated LOS148 -- -- protein kinase (70 kD) (ZAP70) Zeta-chain (TCR) associated LOS148 protein kinase (70 kD) (ZAP70) (low match) Zinc finger protein (HS.47371) 2 U69274 ------Zinc finger protein (Hs.78765) U6964.5 ------Zinc finger protein 10 (KOX1) X78.933 -- (ZNF10) only ZINCFINGER PROTEIN Q15973 124 (HZF-16) (non-exact 51%) Zinc finger protein 124 (HZF- SS4641 16) (ZNF124) (non-exact, 78%) ZINCFINGER PROTEIN P52736 133 Zinc finger protein 136 (clone UO9367 -- -- pHZ-20) (ZNF136) Zinc finger protein 140 (clone UO9368 ------pHZ-39) (ZNF140) Zinc finger protein 140 (clone AFO6086S pHZ-39) (ZNF140) (non exact 59%) Zinc finger protein 140 (clone UO9368 pHZ-39) (ZNF140) (non exact 73%) Zinc finger protein 140 (clone S66508 pHZ-39) (ZNF140) (non exact 73% aa) US 2011/0003295 A1 Jan. 6, 2011 88
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu Zinc finger protein 140 (clone UO9368 pHZ-39) (ZNF140) (non exact, 80%) Zinc finger protein 143 (clone 2 UO985O ------pHZ-1) (ZNF143) Zinc finger protein 143 (clone UO985O pHZ-1) (ZNF143) (low match) Zinc finger protein 148 (pHZ- AFO39019 -- 52) (ZNF148) ZINCFINGER PROTEIN Q13105 151 (MIZ-1 PROTEIN) (low match) Zinc finger protein 173 UO982S B, T ------(ZNF173) Zinc finger protein 192 U57796 (ZNF192) (non-exact, 66%) Zinc finger protein 198 AJ224901 ------(ZNF198) Zinc finger protein 2 (ZNF2) X60152 (low match) Zinc finger protein 200 AFO60866 -- -- (ZNF200) Zinc finger protein 207 6 AFO46OO1 ------+ high in prostate (ZNF207) Zinc finger protein 216 2 AFO62O72 ------(ZNF216) Zinc finger protein 217 AFO41259 Tactivated -- (ZNF217) ZINCFINGER PROTEIN 22 P17026 (ZINC FINGER PROTEIN KOX15) (non-exact 58%) Zinc finger protein 230 U95044 -- (ZNF230) Zinc finger protein 239 L26914 -- -- (ANF239) Zinc finger protein 261 ABOO2383 ------(ZNF261) Zinc finger protein 262 ABOO788S ------(ANF262) Zinc finger protein 263 D88827 (ZNF263) Zinc finger protein 264 ABOO7872 ------(ZNF264) ZINCFINGER PROTEIN Q06730 33A (ZINC FINGER PROTEIN KOX31) (KIAAO065) (HAO946) Zinc finger protein 42 M58297 ------(myeloid-specific retinoic cid responsive) (ZNF42) Zinc finger protein 43 (HTF6) XS9244 (ZNF43) (low match) Zinc finger protein 43 (HTF6) XS9244 (ZNF43) (non-exact, 54%) Zinc finger protein 43 (HTF6) XS9244 (ZNF43) (non-exact, 71%) ZINCFINGER PROTEIN 43 P281 60 (ZINC PROTEIN HTF6) (non-exact 67%) Zinc finger protein 45 (a L75847 only found in testis Kruppel-associated box (KRAB) domain polypeptide) (ZNF45) ZINCFINGER PROTEIN 46 P24278 (ZINC FINGER PROTEIN KUP) (non-exact 62%) US 2011/0003295 A1 Jan. 6, 2011 89
TABLE 2-continued Comparison of 1,800 Unique Genes Identified in the Blood Cell cDNA Library to Genes Previously Identified in Specific Tissues
No. of Accession Tissue Distribution
Gene Identification ESTS No. BI Br H K Li Lu
Zinc finger protein 6 1 XS646S ------(CMPX1) (ZNF6) Zinc finger protein 74 (Coss2) 1 X71623 (ZNF74) (non-exact, 67%) Zinc finger protein 76 1 M91592 ------(expressed in testis) (ZNF76) ZINCFINGER PROTEIN 83 1 P51522 (ZINC FINGER PROTEIN HPF1) (non-exact 65%) Zinc finger protein 84 (HPF2) 1 M27878 Tactivated ------(ZNF84) Zinc finger protein 85 2 U35376 ------(ZNF85)) Zinc finger protein 9 (ZNF9) 5 M28372 ------ZINCFINGER PROTEIN 93 1 P35789 (-ZINC FINGER PROTEIN HTF34) (non-exact 70%) Zinc finger protein C2H2-25 3 U38904 ------(ZNF25) Zinc finger protein clone L3-4 AFO247O6 Zinc finger protein 4 M92843 -- blood only homologous to Zfp-36 in mouse (ZFP36) ZINCFINGER PROTEIN Q03164 HRX (ALL-1) (71% a.a.) Zinc finger protein HZF4 X78927 Zinc finger protein RIZ D4S132 ------Zinc finger protein, Subfamily U4O462 -- 1A, 1 (Ikaros) (LYF1) Zinc finger protein, Subfamily U4O462 1A, 1 (Ikaros) (LYF1) (low match) Zinc finger transcriptional M92844 regulator (GOS24) zinc-finger helicase (hzFH) 2 U91543 ------Zn-15 related zinc finger U223 77 ------protein (rlf) Zn-15 related zinc finger U223 77 protein (rlf) (non-exact 56%) ZNF80-linked ERV9 long X83497 terminal repeat ZW10 (Drosophila) homolog, 2 US4996 centromerefkinetochore protein (ZW10) Zyxin (ZYX) 4 X95735 Column 1: List of unique genes derived from 6,283 known ESTs from blood cells. Column 2: Number of genes found in randomly sequenced ESTs from blood cells, Column 3: Accession number, Column 4: “+” indicates the presence of the unique gene in publicly available cDNA libraries of blood (B1), brain (Br), heart (H), kidney (K), liver (Li) and lung (Lu). **Comparison to previously identified tissue-specific genes was determined using the GenBank of the National Centre of Biotechnology Information (NCBI) Database.
Discussion 0069. For example, isoformic myosin heavy chain genes 0068. Every cell and tissue comprising the human body are known to be generally expressed in cardiac muscle tissue. share the necessary genetic information required to maintain In the rodent, the (My HC gene is only highly expressed in the cellular homeostasis. These “housekeeping genes function fetus and in diseased states Such as overt cardiac hypertrophy, in basic cellular maintenance, including energy metabolism heart failure and diabetes; the (MyHC gene is highly and cellular structure in all cell types. However, in certain expressed shortly after birth and continues to be expressed in situations, even the housekeeping genes show altered expres the adult heart. In the human, however, (My HC is highly Sion. Thus, it is necessary to define the use of these genes as expressed in the Ventricles from the fetal stage through adult internal controls from one investigation to another. Current hood. This highly expressed (MyHC, which harbours several results from the human blood cell EST database indicate that mutations, has been demonstrated to be involved in familial over 50% of the transcripts are widely expressed throughout hypertrophic cardiomyopathy (Geisterfer-Lowrance et al. the human body. Most of the cell or tissue specific genes are 1990). It was reported that mutations of (My HC can be also detectable in blood cells by RT-PCR analysis. detected by PCR using blood lymphocyte DNA (Ferrie et al., US 2011/0003295 A1 Jan. 6, 2011 90
1992). Most recently, it was also demonstrated that mutations transcripts in blood. A kit for diagnosing, prognosing or even of the myosin-binding protein C in familial hypertrophic predicting a disease may be designed using gene-specific cardiomyopathy can be detected in the DNA extracted from primers or probes derived from a whole blood sample for a lymphocytes (Niimura et al., 1998). specific disease and applied directly to a drop of blood. A 0070. Similarly, APP and APC, which are known to be cDNA library specific for a disease may be generated from tissue specific and predominantly expressed in the brain and whole blood samples and used for diagnosis, prognosis or intestinal tract, are also detectable in the transcripts of blood. even predicting a disease. These cell- or tissue-specific transcripts are not detectable by 0074 The following references were cited herein: Northern blot analysis. However, the low number of tran (0075 Claudio J O et al. (1998). Genomics 50:44-52. script copies can be detected by RT-PCR analysis. These (0076 Chelly J et al. (1989). Proc. Nat. Acad. Sci. USA. findings strongly demonstrate that genes preferentially 86:2617-2621. expressed in specific tissues can be detected by a highly 0.077 ChellyJet al. (1988). Nature 333:858-860. sensitive RT-PCR assay. In recent years, evidence has been (0078 Drews J & Ryser S (1997). Nature Biotech. obtained to indicate that expression of cell or tissue-restricted 15:1318-9. genes can be detected in the peripheral blood of patients with metastatic transitional cell carcinoma (Yuasa et al. 1998) and (0079 Ferrie RMetal. (1992). Am. J. Hum. Genet. 51:251 patients with prostate cancer (Gala et al. 1998). 62. 0071 Atrial natriuretic factor (ANF) and Zinc finger pro 0080) Fu D-Jet al. (1998). Nat. Biotech 16:381-4. tein (ZFP), which are known to be highly expressed in heart I0081 Gala J Let al. (1998). Clin. Chem. 44(3):472-81. tissue biopsies and in the plasma of heart failure patients, are I0082 Geisterfer-Lowrance AAT et al. (1990). Cell also detectable in the transcripts of blood. Differential expres 62:999-1OO6. sion of Zinc finger protein among the normal, diabetic and 0.083 Groden Jet al. (1991). Cell 66:589-600. asymptomatic preclinical Subjects may have additional value I0084. Hwang D M et al. (1997). Circulation 96:4146 as a prophylactic “early warning system’. On a related note, 42O3. there is now more attention/discussion in the cardiovascular I0085 Jandreski M A & Liew C C (1987). Hum. Genet. disease field being focused on Syndrome X, loosely defined 76:47-53. as a continuum of hypertension, increasing Sugar levels, dia betes, kidney failure, culminating in heart failure, with the I0086) Jin O et al. (1990). Circulation 82:8-16 possibility of stroke and heart attack at any time in the con I0087 Kimoto Y (1998). Mol. Gen. Genet. 258:233-239. tinuum. The early identification of patients at risk of organ I0088 Koster Metal. (1996). Nat. Biotech 14: 1123-8. failure has been a challenge to the medical community for I0089 Liew & Jandreski (1986). Proc. Nat. Acad. Sci. some time and the present method has the potential of resolv USA. 83:3175-3179 ing or, at least, ameliorating this challenge. (0090 Liew CC et al. (1990). Nucleic Acids Res. 18:3647 0072 The present invention demonstrates that a simple 3651. drop of blood may be used to determine the quantitative 0.091 Liew CC (1993). J Mol. Cell. Cardiol. 25:891-894 expression of various mRNAs that reflect the health/disease 0092. Liew C C et al. (1994). Proc. Natl. Acad. Sci. USA. state of the subject through the use of RT-PCR analysis. This 91:10645-10649. entire process takes about three hours or less. The single drop (0093. Liew et al. (1997). Mol, and Cell. Biochem. 172:81 of blood may also be used for multiple RT-PCR analyses. 87. There is no need for large samples and/or costly and time (0094 Niimura Het al. (1998). New Eng. J. Med. 338: consuming separation of cell types within the blood for this 1248-1257. method as compared to the methods described by Kimoto (1998) and Chelly et al. (1989; 1988). It is believed that the 0.095 Ogawa M (1993). Blood 81:2844-2853. present finding can potentially revolutionize the way that (0096 Santoro I M & Groden J (1997). Cancer Res. diseases are detected, diagnosed and monitored because it 57:488-494. provides a non-invasive, simple, highly sensitive and quick (0097 Yuasa T et al. (1998). Japanese J. Cancer Res. screening for tissue-specific transcripts. The transcripts 89:879-882. detected in whole blood have potential as prognostic or diag 0098. Any patents or publications mentioned in this speci nostic markers of disease, as they reflect disturbances in fication are indicative of the levels of those skilled in the art to homeostasis in the human body. Delineation of the sequences which the invention pertains. Further, these patents and pub and/or quantitation of the expression levels of these marker lications are incorporated by reference herein to the same genes by RT-PCR will allow for an immediate and accurate extent as if each individual publication was specifically and diagnostic/prognostic test for disease or to assess the efficacy individually indicated to be incorporated by reference. and monitor a particular therapeutic. (0099. One skilled in the art will appreciate readily that the 0073. In addition to RT-PCR, other methods of amplifying present invention is well adapted to carry out the objects and may also be used for the purpose of measuring/quantitating obtain the ends and advantages mentioned, as well as those tissue-specific transcripts in human blood. For example, mass objects, ends and advantages inherent herein. The present spectrometry may be used to quantify the transcripts (Koster examples, along with the methods, procedures, treatments, et al., 1996; Fu et al., 1998). The application of presently molecules, and specific compounds described herein are disclosed method for detecting tissue-specific transcripts in presently representative of preferred embodiments, are exem blood does not restrict to Subjects undergoing course of plary, and are not intended as limitations on the scope of the therapy or treatment, it may also be used for monitoring a invention. Changes therein and other uses will occur to those patient for the onset of overt symptoms of a disease. Further skilled in the art which are encompassed within the spirit of more, the present method may be used for detecting any gene the invention as defined by the scope of the claims. US 2011/0003295 A1 Jan. 6, 2011 91
SEQUENCE LISTING
<16O is NUMBER OF SEO ID NOS: 10
<210s, SEQ ID NO 1 &211s LENGTH: 18 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Forward primer of exon1 of insulin gene <4 OOs, SEQUENCE: 1 gccCtctggg gacctgac 18
<210s, SEQ ID NO 2 &211s LENGTH: 18 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Reverse priners of exon 1 and 2 of inslin gene <4 OOs, SEQUENCE: 2 cccacctgca ggit cotct 18
<210s, SEQ ID NO 3 &211s LENGTH: 24 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Forward primer of My HC gene
<4 OOs, SEQUENCE: 3 gctggaacgt agagactic cc tict 24
<210s, SEQ ID NO 4 &211s LENGTH: 24 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Reverse primer of My HC gene <4 OOs, SEQUENCE: 4 ggat.cct tcc agat catcca cittg 24
<210s, SEQ ID NO 5 &211s LENGTH: 2O &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Forward primer of ANF gene <4 OOs, SEQUENCE: 5 ggattt Caag aatttgctgg 2O
<210s, SEQ ID NO 6 &211s LENGTH: 2O &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Reverse primer of ANF gene <4 OOs, SEQUENCE: 6 gCagat.cgat cagaggagtic 2O US 2011/0003295 A1 Jan. 6, 2011 92
- Continued
<210s, SEQ ID NO 7 &211s LENGTH: 2O &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Forward primer of APP gene <4 OO > SEQUENCE: 7 ggatgctt cattgaacgtg
<210s, SEQ ID NO 8 &211s LENGTH: 19 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: reverse primer of APP gene <4 OOs, SEQUENCE: 8 t catt cacac cagcacatg 19
<210s, SEQ ID NO 9 &211s LENGTH: 21 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Forward primer of ZFP gene < 4 OO > SEQUENCE: 9 cacargagric arggtcaacg a 21
<210s, SEQ ID NO 10 &211s LENGTH: 22 &212s. TYPE: DNA <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: Reverse primer for ZFP gene <4 OOs, SEQUENCE: 10 ggattaaaat galagcaccca ga 22
1. A method of profiling gene expression in a human Sub alloprotease domain 8 (ADAMS); Akinase anchor pro ject undergoing a treatment, the method comprising: tein 95 (AKAP95); A kinase anchor protein, 149 kD determining, for each gene of a set of genes, a level of RNA (AKAP149): Absent in melanoma 1 (AIM1); accessory encoded by the gene in a blood sample of the Subject, proteins BAP31/BAP29 (DXS1357E); acetyl-Coen wherein the set comprises the genes identified as: Zyme A acyltransferase (peroxisomal 3-oxoacyl-Coen 100 kDa coactivator; 10 kD protein (BC10): 14-3-3 epsi Zyme A thiolase) (ACAA); acetyl-Coenzyme A trans lon; 14-3-3 protein; 15 kDa selenoprotein (SEP15); porter (ACATN); acidic 82 kDa protein; acidic protein 1-phosphatidylinositol-4-phosphate 5-kinase isoform rich in leucines (SSP29); Aconitase 2, mitochondrial C; 23 kD highly basic protein; 2-5A-dependent RNase: (ACO2); actin binding protein MAYVEN: actin, beta 2'-5' oligoadenylate synthetase 2 (OAS2); 26S protea (ACTB); actin, gamma 1 (ACTG1); actin-binding LIM some subunit 11: 36 kDa phosphothyrosine protein; protein (ABLIM); Actinin, alpha 1 (ACTN1); actinin, 3-phosphoglycerate dehydrogenase (PGAD): 3-prime alpha 4 (ACTN4); activated p21cdc42Hs kinase (ACK); phosphoadenosine 5-prime-phosphosulfate synthase 1 activated RNA polymerase II transcription cofactor 4 (PAPS51); 5-aminoimidazole-4-carboxamide ribo (PC4); activating transcription factor 1 (ATF1); activat nucleotide transformylase; 5'-nucleotidase; 6-phospho ing transcription factor 2 (ATF2); activating transcrip fructo-2-kinase/fructose-2,6-biphosphatase 4 tion factor 4 (tax-responsive enhancer element B67) (PFKFB4); 6-phosphofructo-2-kinase/fructose-2,6-bis (ATF4); active BCR-related gene (ABR); acyl-CoA oxi phosphatase (PF2K); 71 kd heat shock cognate protein dase (AOX), acyl-Coenzyme A dehydrogenase, C-4 to hsc70; 76 kDa membrane protein (P76): 8-oxoguanine C-12 straight chain (ACADM); acyl-Coenzyme A dehy DNA glycosylase (OGG1); a disintegrin and metallo drogenase, very long chain (ACADVL); acyloxyacyl protease domain 10 (ADAM10); a disintegrin and met hydrolase (neutrophil) (AOAH); adaptin, delta