Chromosome 10

Mouse Genome Informatics (MGI 2.8). This site is a comprehensive SNP Consortium. This is the website of the SNP Consortium Ltd, a listing of mammalian homology and comparative maps that public/private collaboration that has to date discovered and allows you to search by gene name or map location, as well as characterized nearly 1.8 million SNPs view whole-genome maps http://snp.cshl.org http://www.informatics.jax.org/menus/homology_menu.shtml UCSC Genome Bioinformatics. The UCSC Genome Bioinformatics National Center for Biotechnology Information (NCBI) dbSNP. site contains working drafts for the human genome and the This site is the single nucleotide polymorphism database main- mouse genome. The Genome Browser and the data it displays are tained by the National Center for Biotechnology Information freely available for academic, nonpro®t and personal use http://www.ncbi.nlm.nih.gov/SNP/ http://genome.ucsc.edu Sanger Centre. This site is the human chromosome 9 sequencing Washington University Genome Center. The focus of the project overview page that reports the sequencing status of the Washington University Genome Center is sequencing human chromosome. The Sanger Centre is a genome research institute and microbial genomes and analysis of genetic variations among funded by the Wellcome Trust populations. This site describes the various sequencing projects http://www.sanger.ac.uk/HGP/Chr9/ and provides progress updates http://www.genome.washington.edu/UWGC/

Chromosome 10 Intermediate article

Nicholas K Moschonas, University of Crete and Institute of Molecular Biology and Article contents Biotechnology (IMBB-FORTH), Crete, Greece  Human Chromosome Characteristics Chromosome 10 is a medium sized submetacentric chromosome corresponding to about  Structure and Statistics of Chromosome 10 Genetic Map and Polymorphisms 4.2% of the genetic material in the genome.   Disease Gene Loci  Cytogenetic Characteristics

Human Chromosome Characteristics 1991). Similarly, HC10 length shown in the Ensembl Table 1 gives details of the characteristics of the human database (see Web Links), i.e. 144.7 Mb, is possibly an chromosome. overestimate and may include artifactual duplications/ overlaps, present in the draft sequence.

Structure and Statistics of Genes Chromosome 10 Euchromatin covers 96.7%of chromosome 10. Based Chromosome size on draft sequence estimations as cited in the UCSC Genome Browser (Web Links), HC10 C ‡ G content is Human chromosome 10 (HC10) is a medium-sized about 41.8%. Investigation along the assembled submetacentric chromosome corresponding to about chromosome sequence using 50 kb windows indicated 4.2%of the total chromosomal length. An overview of a reasonably good correlation between gene density HC10 physical characteristics is shown in the Ensembl and G ‡ C content (Venter et al., 2001). More than genome server (see Web Links). HC10 size estimations 1050 genes have been assigned to HC10, that is 659 based on recent physical mapping and draft genomic protein-coding RefSeq gene entries (see Web Links) deoxyribonucleic acid (DNA) sequencing data give a and 398 `novel' Ensembl genes, resulting in an average total value of approximately 130±133 Mb with a short gene density of about 8 genes/Mb. In addition, 25 (p) arm of 37.0 Mb and a long (q) arm of 92.0 Mb pseudogenes have been assigned to HC10 (RefSeq). A (Bentley et al., 2001; Venter et al., 2001). This estimate higher density, i.e. * 10.5 genes/Mb, was estimated by differs signi®cantly from the 144 Mb value determined the IHGSC (2001) based on the HC10 GeneMap98 previously by less accurate physical methods, such as number of genes. The most gene-rich regions are autoradiography, ¯ow and image cytometry (Morton, 10q23.3±q25.1 and 10q22.1±q23.1. A preliminary

618 NATURE ENCYCLOPEDIA OF THE HUMAN GENOME / &2003 Macmillan Publishers Ltd, Nature Publishing Group / www.ehgonline.net Chromosome 10

Table 1 Characteristics of human chromosome 10.

Characteristic Details Chromosome number 10 Chromosome type Submetacentric Physical size Overall 133.0 Mb Short arm 37.0 Mb Long arm 92.0 Mb Genetic size Overall average 181.7 cM Male average 146.1 cM Female average 209.7 cM Average recombination length 1.37 cM/Mb Physical characteristics Heterochromatic regions Distribution Pericentromeric Length  3.3±4.0 Mb Repetitive sequence content Nature Density (%) Distribution SINEs 12.34 Interspersed LINEs 21.30 Interspersed LTRs 7.50 Interspersed DNA transposons 2.0 Interspersed Variability SNP density 460 SNPs/Mb Microsatellite density  4.0 microsatellites/Mb Euchromatin G ‡ C content 42% CpG density 8.17 CpG islands/Mb Genes Gene density 8 genes/Mb (average) Gene number 1057 Con®rmed 659 Predicted 398 Imprinted gene regions 1 Disease genes 53 Cytogenetic characteristics Chromosome breakpoints 46 Disease related 45 Cancer related 22 Fragile sites 7 Chromosome heteromorphisms 1

cM: centimorgan; DNA: deoxyribonucleic acid; LINEs: long interspersed nuclear elements; LTR: long terminal repeat; Mb: megabase; SINEs: short interspersed nuclear elements; SNP: single nucleotide polymorphism. analysis to classify the molecular function of the tissue-speci®c gene activity and imprinting. Based on current HC10 RefSeq list of genes by exploring HC10 draft sequence data, Venter et al. (2001) published data is presented in Figure 1. About 44.3% identi®ed 1087 CpG islands on HC10, resulting in an of genes (i.e. 292 out of 659) could be classi®ed into 11 average density of 8.17 CpGs/Mb, a value correlating established functional categories. well with the above-mentioned gene density. A slightly higher CpG density, *10.5 CpGs/Mb, was calculated CpG islands by the IHGSC (2001). Interestingly, according to this investigation, the longest CpG island of the human CpG islands in the human genome are considered to be genome (i.e. 36 619 bp) maps to HC10. DNA fragments larger than 200 base pairs (bp) with > 50%G ‡ C content and a ratio of observed versus Human chromosome 10±mouse synteny expected GC dinucleotide frequency of at least 60%. Many CpG islands are adjacent to the 50 end of genes. Comparative gene mapping combined with functional They are of particular importance because their analysis has facilitated the determination of HC10± cytosine methylation state has been correlated with mouse synteny (see NCBI Human±Mouse Homology

NATURE ENCYCLOPEDIA OF THE HUMAN GENOME / &2003 Macmillan Publishers Ltd, Nature Publishing Group / www.ehgonline.net 619 Chromosome 10

25% resolution linkage map data, combined with chromo- some physical mapping and sequence data, provide 20% an ideal tool for effective positional cloning and identi®cation of disease candidate genes. About 524 15% microsatellite markers (i.e. 356 dinucleotide, a penta- 10% nucleotide, 132 tetranucleotide and 35 trinucleotide repeats) have been assigned to HC10. The most 5% informative microsatellite markers together with restriction fragment length polymorphisms (RFLPs) 0% and variant numbers of tandem repeats (VNTRs) have been used for the construction of several high-

Signaling Transport Cell cycle resolution genetic maps (such as those on the Human Metabolism Cytoskeletal Genome Organisation (HUGO) website). Based on Cellular processes Defense/immunity the current estimates of the physical length of the Protein modification DNA/RNA modification chromosome and the size of the corresponding sex- Transcription/translationCell–cell communication average Ge ne thon linkage map (Dib et al., 1996), an Figure 1 Distribution of the molecular function of 292 overall recombination length of 1.37 cM/Mb was chromosome 10 RefSeq genes. calculated. However, a more informative estimation across 3 Mb contiguous chromosomal regions has Map in Web Links). Syntenic regions of genes mapped been made by Venter et al. (2001). This group placed to the 10p arm are mainly on mouse chromosome 2; the corresponding Ge ne thon markers on HC10 chromosomes 18, 13 and 6 are also represented. Genes compartmentalized shotgun assemblies and subse- mapped to the 10q arm have syntenic regions, quently calculated the relative physical distances and particularly on mouse chromosome 19 as well as on rates of recombination. Using this approach, the 14, 10 and 7. average value determined on the sex-average map was 1.29 cM/Mb with a minimum of 0.66 and a maximum Heterochromatin of 3.05 cM/Mb, elegantly con®rming the variability in recombination rates among various regions of the The chromosome 10 pericentromeric heterochromatic chromosome and the high recombination rates in the region is 3.3±4 Mb. Structural analysis of a more than telomeric regions. 1 Mb contiguous pericentromeric sequence, spanning The most frequent genetic variation is a single the transition from centric heterochromatin to euchro- nucleotide polymorphism (SNP) occurring once every matin at 10q11, revealed that the proximal 25%of its 100±300 bases. Most of the genome contains SNPs at length consists of satellite arrays and other tandem high density, relatively constant across the autosomes. repeats separated by tracts of complex sequence The use of SNPs in genetic analysis will accelerate evolved by pericentromeric-directed duplications, particularly the identi®cation of common disease genes whereas the rest contains few chromosome-speci®c by allowing a search for associations between a clinical tandem repeats (Guy et al., 2000). phenotype and speci®c molecular differences for a Chromosome 10 repeats given population group. More than 61 000 SNPs have been identi®ed on HC10 (see SNP Consortium Ltd in Interspersed repeat sequences represent more than Web Links), resulting in an average density of about 43%of the length of chromosome 10 (P. Deloukas and 460 SNPs/Mb or 2.1 kb/SNP. This makes the average E. Birney, unreleased row data of the European SNP density more than 100 times higher than Bioinformatics Institute (EBI)). Short interspersed microsatellite density (4 microsatellites/Mb) underly- nuclear elements (SINEs) represent about 12.34% ing the superiority of SNP-based approaches in human (Alu: 9.60%, mammalian-wide interspersed repeat genetic variation analysis. (MIR): 2.34%and MIR3: 0.40%)long interspersed nuclear elements (LINEs) 21.3%(L1: 18.14%, L2: 2.88%and L3: 0.33%);long terminal repeats (LTRs) 7.5%; and DNA transposons 2%. Disease Gene Loci

Disease-associated genes Genetic Map and Polymorphisms To date, 53 genes mapped to chromosome 10 have Genetic linkage maps are valuable tools in the been associated with 75 genetic disorders, including analysis of the inheritance of human traits. High- various types of solid tumors, hematopoietic and

620 NATURE ENCYCLOPEDIA OF THE HUMAN GENOME / &2003 Macmillan Publishers Ltd, Nature Publishing Group / www.ehgonline.net Chromosome 10 lymphoid malignancies, immune de®ciencies, develop- drome 2, infantile-onset spinocerebellar ataxia, spastic mental malformations, enzyme de®ciencies, disorders paraplegia 9, endometrial carcinoma, lateral temporal of the intermediate metabolism and neurodegenerative lobe partial epilepsy, etc.) with gene loci on chromo- disorders (OMIM). A complete gene list and the some 10 (Table 3). The corresponding genes remain to corresponding clinical phenotypes is presented in be identi®ed. Table 2. Multifactorial disease susceptibility loci Disease-associated loci To date 10 common multifactorial diseases have Molecular genetic and/or cytogenetic analysis has susceptibility loci which map to HC10 (Table 4). revealed linkage of 18 diseases (e.g. DiGeorge syn- Among them, three loci have been associated with

Table 2 Human chromosome 10 disease genes

Chromosomal location Gene Protein OMIM Disease/phenotype

10pter±pter11.2 PHYH Phytanoyl-CoA-hydroxylase 602026 Refsum disease 10p15 GATA3 GATA binding protein 3 131320 Hypoparathyroidism, sensorineural deafness and renal dysplasia 10p15±p14 IL2RA Interleukin 2 receptor alpha chain 147730 Interleukin 2 receptor, alpha, de®ciency of t(10;11)(p12;q23) MLLT10 ± 602409 Acute myeloid leukemia, acute T-cell lymphoblastic leukemia t(10;11)(p13;q21) AF10-CALM ± 96203701a T-cell acute lymphoblastic leukemia (ALL) 10p14 OPTN Optineurin 602432 Glaucoma 1E, primary, open angle, adult onset 10p12.1 CUBN Cubilin 261100 Megaloblastic anemia 1 t(10;11)(p11.2;q23) ABI1-MLL ± 9694699a Acute nonlymphoblastic leukemia (ANLL) 10p11.1 MYO3A Myosin IIIA 606808 Deafness, autosomal recessive 30 10p DCLRE1C DNA cross link repair protein 1c 605988 Severe combined immune de®ciency, Athabascan type 10q11 ERCC1 DNA excision repair protein 133540 Cockayne syndrome, type B 10q11.1 CXCL12 Chemokine, C-X-C motif, ligand 12 600835 AIDS, resistance to 10q11.2 CHAT Choline acetyltransferase 254210 Familial infantile myasthenia gravis 10q11.2 RET RET oncogene 164761 Multiple endocrine neoplasia IIA (MEN2A); Medullary thyroid carcinoma (MTC); Multiple endocrine neoplasia IIB (MEN2B); Hirschsprung disease (HSCR) 10q11.2 NCOA4 Nuclear receptor coactivator 4 601984 Thyroid carcinoma, papillary inv(10)(q11.2q21) RET-H4 (PTC1) ± 601985 Papillary thyroid carcinoma 10q11.2±q21 MBL2 Mannose-binding lectin 2 154545 Chronic infections, as a result of opsonin defect 10q21.1 PCDH15 Protocadherin-15 602083 Usher syndrome type 1F 10q21±q22 CDH23 Cadherin-23 601067 Usher syndrome type 1D 10q21.1±q22.1 EGR2 KROX-20, Drosophila, homolog of 129010 Neuropathy, congenital hypomyelinating, 1; Charcot±Marie±Tooth disease, type 1; Dejerine±Sottas neuropathy 10q21.1±q21.2 ANXA7 Annexin VII 186360 Prostate cancer t(5;10)(q33;q21.2) H4-PDGFRB ± 20365428a Negative chronic myeloid leukemia; Chronic myelomonocytic leukemia 10q22 HK1 Hexokinase 142600 Hemolytic anemia as a result of hexokinase de®ciency 10q22 MAT1A Methionine adenosyltransferase I, alpha 250850 Hypermethioninemia, persistent, autosomal dominant, as a result of methionine adenosyltransferase I/III de®ciency; Methionineadenosyltransferase de®ciency, autosomal recessive 10q22 PCBD Pterin-4a-carbinolamine dehydratase 126090 Hyperphenylalaninemia with primapterinuria 10q22 PRF1 Perforin 170280 Hemophagocytic lymphohistiocytosis, familial

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Table 2 Continued

Chromosomal location Gene Protein OMIM Disease/phenotype

10q22.1 PSAP Prosaposin 176801 Metachromatic leukodystrophy 10q22.3 BMPR1A Bone morphogenetic protein receptor IA 601299 Polyposis, juvenile intestinal 10q23 RGR Retinal G protein-coupled receptor 600342 Retinitis pigmentosa, autosomal recessive and autosomal dominant 10q23±q24 PAPSS2 ATP sulfurylase/APS kinase 2 603005 Spondyloepimetaphyseal dysplasia, Pakistani type 10q23.1±q23.3 HPS1 Hermansky±Pudlak syndrome protein 604982 Hermansky±Pudlak syndrome 10q23.2 BLNK B cell linker protein 604515 Hypoglobulinemia and absent B cells 10q23.3 GLUD1 Glutamate dehydrogenase 1 138130 Hyperinsulinism±hyperammonemia syndrome 10q23.3 PTEN Phosphate and tensin homolog 601728 Cowden disease; Lhermitte±Duclos syndrome; Bannayan±Zonana syndrome; Endometrial carcinoma; Polyposis, juvenile intestinal; Prostate cancer 10q24 ABCC2 ATP-binding cassette, subfamily C, 601107 Dubin±Johnson syndrome member 2 10q24 LGI1 Leucine-rich gene, glioma-inactivated 1 604619 Epilepsy, partial with auditory features; Glioblastoma 10q24 COX15 Cytochrome C oxidase, subunit 15 603646 Cardyomyopathy, hypertrophic, early-onset, fatal 10q24 C10orf2 T7 gene 4-like protein with 606075 Progressive external ophthalmoplegia with intramitochondrial mitochondrial DNA deletions nucleoid localization 10q24 CYP2C9 Cytochrome P-450, subfamily IIC, 601130 Tolbutamide poor metabolizer; member 9 Warfarin sensitivity 10q24.2 CPN1 Carboxypeptidase 1, polypeptide 1, 50kDa 603103 Carboxypeptidase N di®ciency t(10;14)(q24;q11) HOX11-TRD T cell leukemia, homeobox 1 186770 Acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) t(7;10)(q35;q24) HOX11-TRB ± 89323363a Childhood T-cell lymphoblastic leukemia 10q24 RBP4 Retinol-binding protein 4 180250 Retinol binding protein, de®ciency of 10q24±q25 SUFU Suppressor of fused 607035 Medulloblastoma, desmoplastic 10q24±q25 LIPA Lipase A, lysosomal acid, 278000 Wolman disease; Cholesteryl ester cholesterol esterase storage disease 10q24±q26 ADRB1 Adrenergic, beta-1, receptor 109630 Resting heart rate 10q24.1 TNFRSF6 Tumor necrosis factor receptor superfamily 134637 Autoimmune lymphoproliferative syndrome member 6 10q24.1±q24.3 CYP2C19 Cytochrome P-450, subfamily IIC 124020 Mephenytoin poor metabolizer 10q24.3 COL17A1 Collagen XVII, alpha 1 113811 Epidermolysis bullosa, generalized atrophic benign 10q24.3 CYP17A1 Cytochrome P-450, subfamily XVII 202110 Adrenal hyperplasia, congenital, as a result of 17-alpha-hydroxylase de®ciency 10q24.3 PYCS Pyrroline-5-carboxylate synthetase 138250 Hyperammonemia with hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia 10q24.3±q25.1 PAX2 Paired box homeotic gene-2 167409 Optic nerve coloboma with renal disease 10q24.32 HPS0b HPS syndrome-6 protein 607522 Hermansky±Pudlak syndrome 10q25 MXI1 MAX-interacting protein 600020 Neuro®brosarcoma, prostate cancer 10q25 PITX3 Paired-like homeodomain 602669 Anterior segment mesenchymal dysgenesis transcription factor 3 and cataract 10q25.2±q26.3 UROS Uroporphyrinogen III synthase 263700 Porphyria, congenital erythropoietic 10q25.3 TCF4 Transcription factor 7-like 2 602228 Colorectal cancer 10q25.3±q26.1 DMBT1 Deleted in malignant brain tumors 601969 Glioblastoma multiforme; Medulloblastoma 10q26 WDR11 WD repeat-containing protein 11 606417 Glial and other tumors, candidate for

622 NATURE ENCYCLOPEDIA OF THE HUMAN GENOME / &2003 Macmillan Publishers Ltd, Nature Publishing Group / www.ehgonline.net Chromosome 10

Table 2 Continued

Chromosomal location Gene Protein OMIM Disease/phenotype

10q26 FGFR2 Fibroblast growth factor receptor 2 176943 Crouzon, Jackson±Weiss, Beare±Stevenson cutis gyrata, Pfeiffer, Apert and Saethre±Chotzen syndromes 10q26 OAT Ornithine aminotransferase 258870 Gyrate atrophy of choroid and retina with ornithinemia 10q26.1 EMX2 Empty spiracles, Drosophila, homolog of 600035 Schizencephaly 10q26.1 PNLIP Pancreatic lipase 246600 Pancreatic lipase de®ciency 10 NODAL Nodal, mouse, homolog of 601265 Situs ambiguus aPubMed ID (see Web Links). bInterim gene symbol (see LocusLink).

Table 3 Human chromosome 10 disease-associated loci

Locus Disease Mapping OMIM ID

PAC1 Prostate adenocarcinoma pter±q11 601188 DGS2 DiGeorge syndrome/velocardiofacial syndrome complex-2 p14±p13 601362 ARVD6 Arrhythmogenic right ventricular dysplasia-6 p14±p12 604401 THC2 Thrombocytopenia-2 p12±p11.2 188000 UAN Uric acid nephrolithiasis q21±q22 605990 CMD1C Cardiomyopathy, dilated-1C, autosomal dominant q21±q23 601493 MBS3 Moebius syndrome-3 q21.3±q22.1 604185 UFS Urofacial syndrome (Ochoa syndrome) q23±q24 236730 NMSR Neuropathy, motor and sensory, Russe type q23.2 605285 SPG9 Spastic paraplegia-9 q23.3±q24.1 601162 CDB2 Corneal dystrophy, Thiel±Behnke type q24 602082 IOSCA Infantile-onset spinocerebellar ataxia q24 271245 SHFM3 Split hand/foot malformation, type 3 q24 600095 DEC Endometrial carcinoma q26 602084 CLS-like Cof®n±Lowry syndrome like phenotype q25.1±q25.3 11078556a MCC Merkel cell carcinoma q23 11291079a RNANC Retinal nonattachment, nonsyndromic, congenital q21 221900

aPubMed ID (see Web Links).

Alzheimer disease, two with insulin-dependent Cytogenetic Characteristics diabetes mellitus and one with schizophrenia. Chromosomal breakpoint Imprinted gene regions At least 46 breakpoints have been reported for Genomic imprinting, that is the differential expression chromosome 10. Among them, well-characterized of genes depending on their parental origin, seems to translocations resulting in gene fusions have been be a rare genetic event. HC10 imprinted genes have not associated with various forms of leukemia (Table 2). been reported. De novo mutations of RET and FGFR2 Papillary thyroid carcinoma is associated with an genes (Table 2) preferentially occurring during inversion of 10q11.2q21 (Table 2). Several deletions spermatogenesis, are not regarded as an imprinting involving either part of 10p or 10q have been effect. However, evaluation of data from a genome associated with gliomas, and deletions of the distal scan performed using a large number of affected 10q with endometrial carcinoma. DiGeorge and sibling pair families with type 1 diabetes investigated velocardiofacial syndrome 2 results from a deletion of for evidence of predominant sharing of either maternal the p14±p13 region (OMIM ID: 601362). An overview or paternal alleles, has suggested a maternal origin of commonly deleted regions and unbalanced chro- effect for the IDDM10 locus (Table 4). mosome 10 aberrations, including partial monosomy

NATURE ENCYCLOPEDIA OF THE HUMAN GENOME / &2003 Macmillan Publishers Ltd, Nature Publishing Group / www.ehgonline.net 623 Chromosome 10

Table 4 Human chromosome 10 multifactorial disease susceptibility loci

Locus Disease Mapping OMIM ID

LPRS Leprosy p13 246300 IDDM10 Diabetes mellitus, insulin-dependent, 10 p11±q11 601942 IDDM17 Diabetes mellitus, insulin-dependent, 17 q25 603266 OB10P Bulimia nervosa (BN/BULN), susceptibility to 10p 607499 OB10Q Obesity, susceptibility to 10q 607514 AD6 Alzheimer disease q24 605526 Alzheimer disease p12±p14 9653640a Alzheimer disease q11.2±q21 11125144a IBD In¯ammatory bowel disease p 10053016a Schizophrenia p 11126394a Bipolar affective disorder q25±q26 11326307a

aPubMed ID (see Web Links).

Table 5 Fragile sites on human chromosome 10

Name Cytogenetic localization Agenta Frequency GDB IDb

FRA10G 10q11.2±q11.2 Aphidicolin Common 125177 FRA10C 10q21±q21 BrdU Common 119141 FRA10D 10q22.1±q22.1 Aphidicolin Common 119142 FRA10A 10q23.3±q24.2 Folic acid Rare 119139 FRA10B 10q25.2±q25.2 BrdU Rare 119140 FRA10E 10q25.2±q25.2 Aphidicolin Common 119143 FRA10F 10q26.1±q26.1 Aphidicolin Common 119923

aInducing agent used in cell culture for visualization of the corresponding fragile site. bGDB: The Genome Database (see Web Links). and trisomy, has been recently reported (Deloukas understood, delayed replication may play a role in the et al., 2000, and references therein). Severe mental expression of fragile sites. Five common and two rare retardation and multiple congenital anomalies includ- fragile sites have been determined on the 10q arm ing distal arthrogryposis have been associated with (Table 5). The bromodeoxyuridine (BrdU)-induced 10q25±qter monosomy (PubMed ID: 9788726), FRA10B, associated with normal phenotype, together whereas terminal deletion of 10q26 correlates with with its nonfragile allele have been considered mild mental retardation and behavioral dif®culties. A to constitute the ®rst described true chromosomal chromosome 10 variant results from an inversion of polymorphism (OMIM ID: 136620). FRA10B is the pericentromeric region p11.2±q21.2 (PubMed ID: composed of approximately 42-bp-long AT-rich 9402964, a review). Finally, there are at least seven expanded repeats, exhibiting intergenerational and cases of a ring chromosome 10, r(10)(p15q26) associ- somatic instability (Hewett et al., 1998). This is ated with mild retardation (PubMed ID: 7837258) and reminiscent of that observed in expanded trinucleotide a small ring chromosome derived from the most repeats. proximal part of 10p, associated with developmental abnormalities and mild mental retardation (PubMed Chromosome heteromorphisms ID: 8733051). A rare pericentric HC10 heteromorphism visualized Fragile sites by distamycin A/40,6-diamidine-2-phenylindole (DA/ DAPI) ¯uorescence staining has been determined by Chromosome gaps known as fragile sites are occa- examining a group of 50 normal individuals. This sionally observed in characteristic sites on many heteromorphism has been exploited in the cytogenetic chromosomes. Several fragile sites are known to be analysis of a patient with chronic myelogenous heritable variants. Although the molecular basis for leukemia exhibiting a translocation involving chromo- their cytogenetic appearance is not yet completely somes 10 and 1 (PubMed ID: 2004561).

624 NATURE ENCYCLOPEDIA OF THE HUMAN GENOME / &2003 Macmillan Publishers Ltd, Nature Publishing Group / www.ehgonline.net Chromosome 11

References and genomic clones, based on a well-supported genetic map. Cytogenetics and Cell Genetics 79(3±4): 257±265. Bentley DR, Deloukas P, Dunham A, et al. (2001) The physical Simpson L and Parsons R (2001) PTEN: life as a tumor suppressor. maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and Experimental Cell Research 264(1): 29±41. X. Nature 409(6822): 942±943. Wilkie AO, Oldridge M, Tang Z and Maxson Jr RE (2001) Deloukas P, French L, Meitinger T and Moschonas NK (2000) Craniosynostosis and related limb anomalies. Novartis Founda- Report of the Third International Workshop on Human tion Symposium 232: 122±133. Chromosome 10 Mapping and Sequencing 1999. Cytogenetics and Cell Genetics 90: 1±12. Web Links Dib C, Faure S, Fizames C, et al. (1996) A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature Ensembl. An overview of HC10 physical characteristics 380(6570): 152±154. www.ensembl.org/perl/mapview?chr=10 Guy J, Spalluto C, McMurray A, et al. (2000) Genomic sequence and European Bioinformatics Institute. The EBI is a center for research transcriptional pro®le of the boundary between pericentromeric and services in bioinformatics. The institute analyses and satellites and genes on human chromosome arm 10q. Human manages databases of biological data including DNA, protein Molecular Genetics 9: 2029±2042. sequences and macromolecular structures Hewett DR, Handt O, Hobson L, et al. (1998) FRA10B structure www.ebi.ac.uk reveals common elements in repeat expansion and chromosomal Genome Database (GDB) fragile site genesis. Molecular Cell 1(6): 773±781. www.gdb.org International Human Genome Sequencing Consortium (IHGSC) Human Genome Organization (HUGO) (2001) Initial sequencing and analysis of the human genome. http://www.gene.ucl.ac.uk/hugo/ Nature 409: 860±921. LocusLink Morton NE (1991) Parameters of the human genome. Proceedings of http://www.ncbi.nlm.nih.gov/LocusLink/ the National Academy of Sciences of the United States of America NCBI Human±Mouse Homology Map 88: 7474±7476. www.ncbi.nlm.nih.gov/Homology Venter JC, Adams, MD, Myers EW, et al. (2001) The sequence of the Online Mendelian Inheritance in Man (OMIM). This database is a human genome. Science 291: 1304±1351. catalog of human genes and genetic disorders www3.ncbi.nlm.nih.gov/Omim/ Further Reading PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi Alfred J (2001) Alzheimer hotspot on 10. Nature Reviews Genetics RefSeq. The NCBI Reference Sequence project (RefSeq) provides 2(2): 89. referencesequencestandards for thenaturallyoccurringmolecules Deloukas P, Schuler GD, Gyapay G, et al. (1998) A physical map of of the central dogma, from chromosomes to mRNAs to proteins 30,000 human genes. Science 282(5389): 744±746. http://www.ncbi.nlm.nih.gov/LocusLink/refseq.html Gardiner-Garden M and Frommer M (1989) CpG islands in SNP Consortium Ltd. Single nucleotide polymorphisms (SNPs) are vertebrate genomes. Journal of Molecular Biology 196: 261±282. common DNA sequence variations among individuals and have Jhiang SM (2000) The RET proto-oncogene in human cancers. great signi®cance for biomedical research Oncogene 20; 19(49): 5590±5597. http://snp.cshl.org Marzella R, Kokkinaki MA, Kapsetaki M, et al. (1997) Map UCSC Genome Browser integration at human chromosome 10: molecular and cytogenetic http://genome.ucsc.edu/cgi-bin/hgGateway?db=hg10 analysis of a chromosome-speci®c somatic cell hybrid panel

Chromosome 11 Intermediate article

Daniela S Gerhard, Office of Cancer Genomics, NCI, Bethesda, Maryland, USA Article contents

Human chromosome 11 is a submetacentric chromosome that contains some 4% of the  Human Chromosome Characteristics  Sequencing genome and a number of imprinted genes.  G 1 C Content  Repeat Sequences Human Chromosome Characteristics  Genetic Map  Genes Table 1 gives details of the characteristics of  Translocations chromosome 11.  Human/Mouse Synteny

Sequencing and sequencing resources. Unfortunately, this `lead' evaporated when a more systematic approach was The sequencing of chromosome 11 is still far from applied to the other chromosomes but not this one. complete. As of September 2001, only 36%of the Therefore many of the details on gene number, single chromosome was completed. In the 1990s, it was one of nucleotide polymorphism (SNP) frequency etc. will the most studied chromosomes with excellent mapping rapidly become obsolete. The interested reader should

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