DOCSLIB.ORG

A One Centimorgan Deletion Unit on Chromosome Xq12 Is Commonly Lost in Borderline and Invasive Epithelial Ovarian Tumors

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A One Centimorgan Deletion Unit on Chromosome Xq12 Is Commonly Lost in Borderline and Invasive Epithelial Ovarian Tumors Oncogene (1998) 16, 197 ± 202 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors MI Edelson1, CC Lau4, CV Colitti1, WR Welch2, DA Bell3, RS Berkowitz1 and SC Mok1 1Laboratory of Gynecologic Oncology, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, and 2Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, 02115; 3Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114; 4Division of Hematology-Oncology, Texas Children's Hospital, Houston, Texas, 77030, USA We have used polymerase chain reaction (PCR) have been unable to detect any signi®cant level of ampli®cation of tandem repeats to study the pattern of genetic alterations speci®c to borderline tumors allelic loss on chromosome X11.2-q12 in borderline and emphasizing the possible separate pathogenesis of invasive epithelial ovarian tumors. Using eight micro- these tumors (Rodabaugh et al., 1995b; Wertheim et satellite markers spanning Xq11.2-q12, 41 borderline and al., 1994; Tangir et al., 1996; Rodabaugh et al., 1995a; 65 invasive ovarian tumors, together with their corre- Dodson et al., 1993; Kim et al., 1994). Recently, Zheng sponding normal tissues, were analysed. The highest et al. have demonstrated that 50% of informative percentage of loss of heterozygosity (LOH) was observed borderline tumors (eight of 16 informative cases) and at the DXS1194 locus in borderline tumors (four of 16 approximately 44% of high grade IEOC displayed informative cases, 25%) and at the androgen receptor LOH at the androgen receptor (AR) locus in the (AR) locus in invasive epithelial ovarian tumors (18 of 47 proximal portion of chromosome Xq (Cheng et al., informative cases, 38%). X chromosome activation 1996). These results suggest that LOH in this region studies performed in cases with LOH at the AR locus may be important for the development of borderline showed that the allelic loss at the AR locus is not tumors and high grade invasive epithelial ovarian con®ned to the inactive allele. A one centimorgan region carcinomas. including the AR locus and ¯anked by the primers In this study, we report the construction of a DXS1161 and PGK1P1 was identi®ed as the smallest detailed deletion map of chromosome Xq11.2-q12 common loss region in both borderline and invasive from 41 borderline tumors and 65 invasive epithelial epithelial ovarian tumors. ovarian carcinomas using eight microsatellite markers in an eort to more accurately localize a region(s) Keywords: ovary; cancer; borderline; loss of hetero- which may be involved in the development of zygosity; chromosome Xq borderline ovarian tumors and invasive EOC. Results Introduction LOH in Xq11.2-Xq12 Borderline ovarian tumors, also known as ovarian epithelial tumors of low malignant potential, are a A set of eight microsatellite markers spanning the distinct entity within the classi®cation of ovarian region from Xq11.2 to Xq12 (Figure 1) was used to neoplasms. These tumors have a histological appear- perform the LOH study on 41 borderline ovarian ance and biologic behavior which are intermediate tumors and 65 invasive epithelial ovarian carcinomas between benign and frankly malignant ovarian with various stages and grades. All cases showed neoplasms (Scully, 1982). While these tumors are interstitial LOH for several of the microsatellite loci cytologically malignant with evidence of cellular tested. LOH aecting at least one locus was observed pleomorphism, they do not exhibit any stromal in 29% of the borderline tumors (12 of 41 informative invasion. A prolonged survival is expected with these cases) and 34% of the invasive epithelial carcinomas tumors even without the use of chemotherapy (22 of 65 informative cases). The LOH results derived (Bostwick et al., 1986; Barakat, 1994; Leake, 1992; from paran embedded tissue and frozen materials Leake et al., 1992; Casey et al., 1993). were not dierent statistically, and thus were combined Genetic studies have been used to understand the in the analysis of both borderline ovarian tumors and biology of ovarian cancers. Loss of heterozygosity invasive epithelial ovarian carcinomas. Figure 2 shows (LOH) studies have been used to detect allelic losses of autoradiographs of ®ve borderline tumor cases speci®c chromosomes in order to identify possible depicting LOH at the AR locus in the tumor lane tumor suppressor genes which may be relevant to the with the normal control in the adjacent lane. development of ovarian cancer. While many of these studies have focused on invasive epithelial ovarian LOH in borderline tumors carcinomas, only a few studies have examined genetic alterations of borderline ovarian tumors. These studies The percentage of tumors with allelic loss at each locus for borderline tumors is shown in Figure 1. The highest Correspondence: SC Mok percentage of LOH was observed at DXS1213 (four of Received 8 February 1997; revised 5 August 1997; accepted 6 August 16 informative cases, 25%) and at the AR locus (seven 1997 of 30 informative cases, 23%). All other loci showed a Deletion mapping of chromosome Xq in ovarian cancer MI Edelson et al 198 Figure 1 Summary of the loci, map position, and frequency of loss of heterozygosity at Xq11.2-q12 in borderline ovarian tumors and invasive epithelial ovarian carcinomas mately one centimorgan, is located between the markers DXS1161 and PGK1P1. The identi®cation of B5 B43 333 466 470 this region was based on the study of cases 315, 317, T N T N T N T N T N 416 and 490 (Figure 4). AR LOH with respect to grade, stage and histological type Clinicopathological characteristics of the tumors were analysed based on allelic loss at the AR locus (Table Figure 2 Autoradiographs of PCR ampli®cations of DNA from 1). No signi®cant dierence was observed between paran blocks (patients B5 and B43) and frozen materials LOH rate at the androgen receptor locus and stage or (patients 333, 466, 470) for borderline ovarian tumors at the androgen receptor (AR) locus. T, tumor DNA; N, normal DNA; tumor type for borderline tumors. Similar analysis for Allelic loss is visualized in the tumor lanes invasive epithelial ovarian carcinomas did reveal a statistically signi®cant dierence of allelic loss at the AR locus for Stage III/IV tumors (P=0.04) and serous much lower percentage of LOH. A one centimorgan tumors (P=0.02). Comparison of LOH rate at the AR region including the AR locus and ¯anked by the locus between borderline tumors (23%), low grade primers DXS1161 and PGK1P1 was identi®ed as the carcinomas (32%), and high grade carcinomas (53%) smallest common loss region using selected cases which did not reveal any statistical dierence (P=0.10), showed restricted LOH patterns (Figure 3). Cases B5, though a trend towards a greater frequency of LOH 466, and 543 speci®cally show LOH at the AR locus at the AR locus with less dierentiated tumors was and no LOH at the ¯anking primers DXS1161 and observed. PGK1P1. No selective loss of the inactive allele at the AR locus LOH in invasive epithelial ovarian carcinomas Selected paired normal and tumor DNA from cases Similar to the borderline tumors, the AR locus showed which showed LOH at the AR locus were subjected to the highest percentage of allelic loss (18 of 47 HpaII restriction enzyme digestion to evaluate whether informative cases, 38%, Figure 1). However, the the lost allele is active or inactive. After digestion, the ¯anking primers showed a higher percentage of LOH remaining allele of cases 324, 336, 490, 528, 545 and in the invasive epithelial ovarian carcinomas as 558 disappeared after digestion suggesting that in these compared to the borderline tumors. Five cases (ES-3, cases the inactive AR allele was lost (Figure 5a). In 351, 384, 528 and 545) showed allelic loss at almost all contrast, the remaining allele of cases 332, 384, and 386 the loci suggesting that these samples had LOH in the could still be observed, suggesting that the active AR whole Xq11.2-q12 region. Therefore, these cases were allele was lost in these cases (Figure 5b). When DNA not informative for the localization of the smallest from normal tissue from cases 324, 332, 386, 490, 528, region of allelic loss. The remaining 17 cases showed and 558 were digested with HpaII, a skewing pattern of restricted LOH patterns which allowed us to de®ne the the two AR alleles was observed. This was particularly smallest common loss region. This region, approxi- evident in case 386 suggesting a relatively selective X- Deletion mapping of chromosome Xq in ovarian cancer MI Edelson et al 199 Figure 3 Deletion map of 12 borderline ovarian tumors. Shaded region indicates loss of region. Primers used in the PCR reaction are listed above. For map of location of the primers, see Figure 1. L, loss of heterozygosity. N, no loss. U, uninformative Figure 4 Deletion map of 22 invasive epithelial ovarian carcinomas. Shaded region indicates loss of region. Primers used in the PCR reaction are listed above. For map of location of the primers, see Figure 1. L, loss of heterozygosity. N, no loss. U, uninformative chromosome inactivation in the normal tissue of these Table 1 Relationship between allelic loss for androgen receptor loci cases. and clinicopathologic characteristics in 30 borderline ovarian tumors and 47 invasive epithelial ovarian carcinomas Invasive The AR allele was not totally deleted in a majority of epithelial ovarian cases that showed LOH Clinico- Borderline tumors carcinomas pathologic LOH No loss LOH No loss To evaluate whether loss of heterozygosity observed at characteristics (n=7) (n=23) P (n=18) (n=29) P the AR locus was due to total allelic deletion or Stage deletion with the replacement by the remaining allele, I/II 7 18 1 13 we performed multiplex PCR.
Load more

Recommended publications
  • Heredity in Sarcoidosis: a Registry-Based Twin Study Thorax: First Published As 10.1136/Thx.2007.094060 on 5 June 2008
    Sarcoidosis Heredity in sarcoidosis: a registry-based twin study Thorax: first published as 10.1136/thx.2007.094060 on 5 June 2008. Downloaded from A Sverrild,1 V Backer,1 K O Kyvik,2 J Kaprio,3 N Milman,4 C B Svendsen,5 S F Thomsen1 1 Department of Respiratory ABSTRACT Prevalence and incidence are dependent on age, sex Medicine, Bispebjerg University Background: Sarcoidosis is a multiorgan granulomatous and ethnicity.1 2 8–10 Hospital, Copenhagen, Denmark; The present understanding of the pathogenesis 2 Institute of Regional Health inflammatory disease of unknown aetiology. Familial Research Services and The clustering of cases and ethnic variation in the epidemiol- of the disease is that sarcoidosis is triggered by an Danish Twin Registry, University ogy suggests a genetic influence on susceptibility to the abnormal immune response to an environmental of Southern Denmark, Odense, agent in a genetically predisposed individual.1 3 disease. This paper reports twin concordance and Denmark; The Finnish Twin heritability estimates of sarcoidosis in order to assess the Genetic factors are considered to contribute to Cohort Study, Department of Public Health, University of overall contribution of genetic factors to the disease the development of sarcoidosis for two main 12610 Helsinki, Helsinki, Finland and susceptibility. reasons ; (1) epidemiological studies have Department of Mental Health Methods: Monozygotic and dizygotic twins enrolled in identified ethnicity as an important risk factor; and Alcohol Research, National the Danish and the Finnish population-based national twin and (2) familial clustering of cases has been Public Health Institute, Helsinki, 4 observed frequently over the last decades.
    [Show full text]
  • National Longitudinal Study of Adolescent to Adult Health
    Social, Behavioral, and Biological Linkages Across the Life Course Social, Behavioral, and Biological Linkages Across the Life Course School Sampling Frame = QED National Longitudinal Study of HS Adolescent to Adult Health HS HS HHS HS Feeder Feeder Feeder Feeder Feeder Sampling Frame of Adolescents and Parents N = 100,000+ (100 to 4,000 per pair of schools) Ethnic High Educ Samples National Academy of Sciences Workshop Black Disabled Sample February 10-11, 2014 Saturation Puerto Rican Samples from 16 Schools Chinese Guidelines for Returning Individual Results from Genome Research Using Population- Main Sample 200/Community Based Banked Specimens Genetic CubanCuban Samples Carolyn Tucker Halpern University of North Carolina at Chapel Hill Unrelated Pairs Identical Twins Fraternal Twins Full Sibs Half Sibs in Same HH Social, Behavioral, and Biological Linkages Across the Life Course Social, Behavioral, and Biological Linkages Across the Life Course In-School In-Home Administration Administration Race and Ethnic Diversity in Add Health Wave I School Adolescents Race/Ethnicity N Unwtd. % Students Parent 1994-1995 Admin in grades 7-12 90,118 17,670 Mexico 1,767 8.5 (79%) 144 20,745 Cuba 508 2.5 Wave II School Adolescents Central-South America 647 3.1 1996 Admin in grades 8-12 Puerto Rico 570 2.8 (88.6%) 128 14,738 China 341 1.7 Wave III Young Adults Philippines 643 3.1 Partners 2001-2002 Aged 18-26 1,507 Other Asia 601 2.9 (77.4%) 15,197 Black (Africa/Afro-Caribbean) 4,601 22.2 Wave IV Adults Non-Hispanic White (Eur/Canada) 10,760 52.0 IIV
    [Show full text]
  • Segregation Distortion and the Evolution of Sex-Determining Mechanisms
    Heredity (2010) 104, 100–112 & 2010 Macmillan Publishers Limited All rights reserved 0018-067X/10 $32.00 www.nature.com/hdy ORIGINAL ARTICLE Segregation distortion and the evolution of sex-determining mechanisms M Kozielska1,2, FJ Weissing2, LW Beukeboom1 and I Pen2 1Evolutionary Genetics, University of Groningen, Haren, The Netherlands and 2Theoretical Biology, University of Groningen, Haren, The Netherlands Segregation distorters are alleles that distort normal segre- selection pressure, allowing novel sex-determining alleles to gation in their own favour. Sex chromosomal distorters lead spread. When distortion leads to female-biased sex ratios, a to biased sex ratios, and the presence of such distorters, new masculinizing gene can invade, leading to a new male therefore, may induce selection for a change in the heterogametic system. When distortion leads to male-biased mechanism of sex determination. The evolutionary dynamics sex ratios, a feminizing factor can invade and cause a switch of distorter-induced changes in sex determination has only to female heterogamety. In many cases, the distorter- been studied in some specific systems. Here, we present a induced change in the sex-determining system eventually generic model for this process. We consider three scenarios: leads to loss of the distorter from the population. Hence, the a driving X chromosome, a driving Y chromosome and a presence of sex chromosomal distorters will often only be driving autosome with a male-determining factor. We transient, and the distorters may remain unnoticed. The role investigate how the invasion prospects of a new sex- of segregation distortion in the evolution of sex determination determining factor are affected by the strength of distortion may, therefore, be underestimated.
    [Show full text]
  • Due to Broad-Sense Genetic Heritability
    The Sociology of Heritability How (and Why) Sociologists Should Care About Heritability: Evidence from Misclassified Twins Dalton Conley* Emily Rauscher NYU & NBER NYU * To whom correspondence should be directed; 6 Washington Square North Room 20; New York, NY 10003. [email protected] The Sociology of Heritability Abstract We argue that despite many sociologists’ aversion to them, heritability estimates have critical policy relevance for a variety of social outcomes ranging from education to health to stratification. However, estimates have traditionally been plagued by genetic-environmental covariance, which is likely to be non-trivial and confound estimates of narrow-sense (additive) heritability for social and behavioral outcomes. Until recently, there has not been an effective way to address this concern and as a result, sociologists have largely dismissed the entire enterprise as methodologically flawed and ideologically-driven. Indeed, in a classic paper, Goldberger (1979) shows that by varying assumptions of the GE-covariance, a researcher can drive the estimated heritability of an outcome, such as IQ, down to zero or up close to one. Survey questions that attempt to measure directly the extent to which more genetically similar kin (such as monozygotic twins) also share more similar environmental conditions than, say, dizygotic twins, represent poor attempts to gauge a very complex underlying phenomenon of GE-covariance. Methods that rely on concordance between interviewer classification and self- report offer similar concerns about validity. In the present study, we take advantage of a natural experiment to address this issue from another angle: Misclassification of twin zygosity in the National Longitudinal Survey of Adolescent Health (Add Health).
    [Show full text]
  • Efficient Introduction of Specific Homozygous and Heterozygous
    LETTER doi:10.1038/nature17664 Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9 Dominik Paquet1*, Dylan Kwart1*, Antonia Chen1, Andrew Sproul2†, Samson Jacob2, Shaun Teo1, Kimberly Moore Olsen1, Andrew Gregg1,3, Scott Noggle2 & Marc Tessier-Lavigne1 The bacterial CRISPR/Cas9 system allows sequence-specific gene prokaryotes12. As the efficacy of potential blocking mutations has not editing in many organisms and holds promise as a tool to generate been systematically studied in eukaryotic cells, we tested their effect models of human diseases, for example, in human pluripotent on HDR accuracy in wild-type human induced pluripotent stem stem cells1,2. CRISPR/Cas9 introduces targeted double-stranded cells (iPS cells) (Extended Data Fig. 1) and, for comparison, human breaks (DSBs) with high efficiency, which are typically repaired embryonic kidney (HEK293) cells. We introduced Cas9–eGFP and by non-homologous end-joining (NHEJ) resulting in nonspecific single guide RNA (sgRNA) plasmids together with five pooled repair insertions, deletions or other mutations (indels)2. DSBs may ssODN templates, which in addition to the APPSwe or PSEN1M146V also be repaired by homology-directed repair (HDR)1,2 using pathogenic mutation also contained a putative silent CRISPR/ a DNA repair template, such as an introduced single-stranded Cas-blocking mutation in the PAM or guide RNA target sequence, oligo DNA nucleotide (ssODN), allowing knock-in of specific or a control non-blocking mutation outside those regions (Fig. 1b, c mutations3. Although CRISPR/Cas9 is used extensively to and Supplementary Tables 1 and 2). engineer gene knockouts through NHEJ, editing by HDR remains We analysed genomic loci of Cas9–eGFP-expressing cells by inefficient3–8 and can be corrupted by additional indels9, preventing next-generation sequencing and determined the fraction of HDR its widespread use for modelling genetic disorders through reads that were ‘accurate’, that is, without undesirable indel modi- introducing disease-associated mutations.
    [Show full text]
  • The Evolution of the Y Chromosome with X-Y Recombination
    Copyright 8 1988 by the Genetics Society of America The Evolution of the Y Chromosome With X-Y Recombination Andrew G. Clark Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802 Manuscript received October 18, 1987 Revised copy accepted March 11, 1988 ABSTRACT A theoretical population genetic model is developed toexplore the consequences of X-Y recombination in the evolution of sex chromosome polymorphism. The model incorporates one sex-determining locus and one locus subject to natural selection. Both loci have two alleles, and the rate of classical meiotic recombination between the loci is r. The alleles at the sex-determining locus specify whether the chromosome is X or Y, and the alleles at the selected locus are arbitrarily labeled A and a. Natural selection is modeled as a process of differential viabilities. The system can be expressed in terms of three recurrence equations, one for the frequency of A on the X-bearing gametes produced by females, one for each of the frequency of A on the X- and Y-bearing gametes produced by males. Several special cases are examined, including X chromosome dominance and symmetric selection. Unusual equilibria are found with the two sexes having very different allele frequencies at the selected locus. A significant finding is that the allowance of recombination results in a much greater opportunity for polymorphism of the Y chromosome. Tighter linkage results in a greater likelihood for equilibria with a large difference between the sex chromosomes in allele frequency. key factor in the evolution of dimorphic sex autosomes, and found that a necessary condition for A chromosomes is the suppression ofrecombi- invasion is that different allele frequencies in the two nation between the proto-X and Y chromosomes.
    [Show full text]
  • Non-Darwinian Evolution in Natural Populations of Drosophila
    DARWINIAN VERSUS NON-DARWINIAN EVOLUTION IN NATURAL POPULATIONS OF DROSOPHILA FRANCISCO J. AYALA UNIVERSITY OF CALIFORNIA, DAVIS 1. Scientific hypotheses: natural selection The goal of science is to discover patterns of relations among recorded phe- nomena, so that a few principles can explain a large number of propositions concerning these phenomena [2]. The scientific value of a theory depends on its explanatory power, that is, on its ability to encompass many subsidiary hy- potheses into a single comprehensive set of mutually consistent principles. But in order to be accepted in science the applicability of a theory needs to be demonstrated. Demonstration, or proof, of a hypothesis or theory concerning the empirical world is a gradual process which is never irrevocably completed. The process of demonstration requires, first, to show that the hypothesis or theory is consistent with the relevant facts. Moreover, the hypothesis or theory needs to be con- firmed by empirical tests. Empirical tests are experiments or observations which may conceivably have diverse outcomes only some of which are compatible with the hypothesis tested while most of them would lead to its rejection. If the tests are of such a nature that any conceivable outcome or state of affairs be com- patible with the hypothesis tested they contribute nothing to the scientific verification of the hypothesis. The value of an empirical test is measured by the a priori likelihood of its outcome being incompatible with the hypothesis. The synthetic theory of evolution, or the theory of evolution by natural selec- tion has a considerable explanatory power. The central concept of the theory is the principle of natural selection-the differential reproduction of genetic vari- ants.
    [Show full text]
  • Mutated MYD88 Zygosity and CXCR4 Mutation Status Are Important Determinants of Ibrutinib Response and Progression Free Survival in Waldenstrom’S Macroglobulinemia
    Mutated MYD88 zygosity and CXCR4 mutation status are important determinants of ibrutinib response and progression free survival in Waldenstrom’s Macroglobulinemia. Treon SP, Tsakmaklis N, Meid K, Yang G, Chen JG, Liu X, Chen J, Demos M, Patterson CJ, Dubeau T, Gustine J, Castillo JJ, Advani R, Palomba M.L., Xu L, and Hunter ZR. Bing Center for Waldenstrom’s Macroglobulinemia, Dana Farber Cancer Institute; Harvard Medical School, Boston MA USA; Stanford University Medical Center, Stanford CA; Memorial Sloan Kettering Cancer Center, New York NY. Abstract Whole genome sequencing first identified MYD88 homozygosity is more common in Table 1. Baseline characteristics of patients. acquired UPDs at 3p22 in WM patients that previously treated patients with CXCR4 Age BM IgM IgA IgG Hb Serum B2M Prior Ratio of Background: Activating somatic mutations in MYD88 and CXCR4 are present in confer MYD88 homozygosity. mutations. Involvement % Therapies Relapsed / 90-95% and 30-40% of untreated WM patients, respectively. Nearly all MYD88 Refractory somatic mutations involve a single nucleotide mutation that results in a change MYD88Mut/WT 64 80 4045 26 349 9.7 5.5 2 0.50 from leucine to proline at amino acid position 265, and most are heterozygous. In CXCR4WT Untreated approximately 10-12% of untreated WM patients, MYD88 L265P is homozygous WM Patients (N=18) Mut/WT due to an acquired uniparenteral disomy (aUPD) or copy number alterations, is (N = 138) MYD88 67 60 3505 25 369 10.8 5.2 2 0.66 more common in previously treated WM patients and associated with CXCR4 CXCR4Mut mutations. (Treon et al, NEJM 2012; Poulain et al, Blood 2013; Tsakmaklis et al, (N=6) MYD88Mut/Mut 61 70 3935 33 528 12.1* 3.0* 1 0.66 IWWM-9, 2016).
    [Show full text]
  • USER GUIDE Contents
    USER GUIDE Contents 1. Purpose and Objective 3 2. How to access CentoLSD™ 3 3. Understanding CentoLSD™ homepage 3 4. Selection of the gene of interest 5 5. Search and filter queries 5 6. Variant review 7 7. Glossary 8 1. Purpose and Objective CentoLSD™ is a software product designed, developed and maintained by CENTOGENE AG. CentoLSD™ is a holistic database that combines phenotype and genotype information gathered from samples of individuals analyzed at CENTOGENE AG. Every variant reported in CentoLSD™ is linked to at least one clinically described case tested against Gaucher or Fabry disease through a validated and accredited laboratory workflow. CentoLSD™ is a growing database; newly analyzed variants will be added quarterly. This user guide has been designed to provide detailed instructions for the proper use of CentoLSD™ in order to query, access and retrieve information from CENTOGENE AG’s lysosomal storage disease (LSD) database. The following chapters provide step-by-step instructions for the use of CentoLSD™. Additionally, you will find a glossary of terms and definitions in the attached appendix. 2. How to access CentoLSD™ To access CentoLSD™ go on use https://www.centogene.com/centolsd. The database is free avaible and no log in is required. 3. Understanding CentoLSD™ homepage The primary CentoLSD™ homepage is a result table –centric display that organizes information for all identified GBA (by default) genetic variants. On the top of the result table, you can download CentoLSD™-related documents, and find options to perform search queries (Figure 1). 3 Related documents Gene selection Gene- related details Searching / filters Definitions / more details Variant result table FIGURE 1 - Homepage organization Terms linked to the symbol i provide their corresponding definition; in order to understand the terminology, simply press the i symbol and a new window opens (see Figure 2 as example).
    [Show full text]
  • Definitive Methods of Zygosity Determination in Twins: Relevance to Problems in the Biology of Twinning INTRODUCTION
    Acta Genet Med Gemellol 39: 459-471 (1990) ©1990 by The Mendel Institute, Rome Sixth International Congress on Twin Studies Definitive Methods of Zygosity Determination in Twins: Relevance to Problems in the Biology of Twinning G.A. Machin Department of Pathology, W.C. Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Canada Abstract. Many studies of embryogenesis and fate of twin pregnancies are invalidated because zygosity is not determined definitively, or is assumed on the basis of inadequate criteria. This paper briefly reviews methods of zygosity determination. It reports published results and a new series of twins in which zygosity was determined by DNA fingerprinting. Implications for methods of prenatal diagnosis of zygosity are discussed in the context of the occasional need for intervention in twin transfusion syndrome or in twins discordant for major malformations. Definitive zygosity and placental anatomy (number of chorions and amnions) is discussed as the firm substrate for studies of nor­ mal and abnormal twin development. Key words: Diseases of twins, MZ twins, Zygosity, Malformations, DNA fingerprin­ ting INTRODUCTION Concerning congenital anomalies in twins, there are three main discussion points: 1) Are anomalies more common in monozygotic (MZ) than dizygotic (DZ) twins? (Anomalies should not be confused with malformations). 2) If anomalies are more common in MZ than DZ twins, are there special types of anomalies? 3) How can concordance/discor­ dance for anomalies in MZ twins best be used to investigate the etiology and pathogenesis of these anomalies, eg, between genetic and extrinsic teratogenic causes? These questions are only being clarified rather slowly for several reasons, including: 1) the relatively small numbers of cases of anomalous twins that can be investigated by any given institution; 2) the need to classify accurately the different types of anomalies Downloaded from https://www.cambridge.org/core.
    [Show full text]
  • Bt Zygosity in Maize Hybrids
    i UNIVERSIDADE ESTADUAL PAULISTA – UNESP CÂMPUS DE JABOTICABAL BT ZYGOSITY IN MAIZE HYBRIDS Kian Eghrari Moraes Agronomist 2020 ii UNIVERSIDADE ESTADUAL PAULISTA – UNESP CÂMPUS DE JABOTICABAL BT ZYGOSITY IN MAIZE HYBRIDS Kian Eghrari Moraes Advisor: Prof. Dr. Gustavo Vitti Môro Co-advisor: Prof. Dr. Odair Aparecido Fernandes Co-advisor: Prof. Dr. Bruno Henrique Sardinha de Souza Tese apresentada à Faculdade de Ciências Agrárias e Veterinárias – Unesp, Câmpus de Jaboticabal, como parte das exigências para a obtenção do título de Doutor em Agronomia (Genética e Melhoramento de Plantas) 2020 iii M827b Moraes, Kian Eghrari Bt zygosity in maize hybrids / Kian Eghrari Moraes. -- Jaboticabal, 2020 96 p. : il., tabs. Tese (doutorado) - Universidade Estadual Paulista (Unesp), Faculdade de Ciências Agrárias e Veterinárias, Jaboticabal Orientador: Gustavo Vitti Môro Coorientador: Odair Aparecido Fernandes 1. Breeding. 2. Spodoptera. 3. Transgenic organisms. I. Título. Sistema de geração automática de fichas catalográficas da Unesp. Biblioteca da Faculdade de Ciências Agrárias e Veterinárias, Jaboticabal. Dados fornecidos pelo autor(a). Essa ficha não pode ser modificada. iv v AUTHOR’S INFORMATION Kian Eghrari Moraes, born on July 2nd, 1990, in Araguari, MG, Brazil, has a bachelor’s degree in Agronomy from the Federal University of Uberlandia (2014). In his master’s dissertation he was a pioneer in the study of Bt zygosity in maize hybrids and got his degree in Agronomy (genetics and plant breeding) at the Sao Paulo State University (2017). Kian was a visiting and research scholar for one year at the University of Illinois at Urbana-Champaign (2019) conducting research on genomics, maize breeding, statistics, and genome editing via CRISPR/Cas9.
    [Show full text]
  • Zygosity Determination in Newborn Twins Using DNA Variants
    J Med Genet: first published as 10.1136/jmg.22.4.279 on 1 August 1985. Downloaded from Journal of Medical Genetics 1985, 22, 279-282 Zygosity determination in newborn twins using DNA variants CATHERINE DEROM*, EGBERT BAKKERt, ROBERT VLIETINCK*, ROBERT DEROMt, HERMAN VAN DEN BERGHE*, MICHEL THIERYt, AND PETER PEARSONt From *the Division ofHuman Genetics, Department ofHuman Biology, Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium; tthe Department ofHuman Genetics, Sylvius Laboratories, State University of Leiden, Wassenaarseweg 72, PB 9503, NL-2300 RA Leiden, The Netherlands; and #the Department of Obstetrics, State University of Gent, De Pintelaan 185, B-9000 Gent, Belgium. SUMMARY A prerequisite for the optimal use of the twin method in human genetics is an accurate determination of the zygosity at birth. This diagnosis is sometimes hampered by the lack of available specific markers. We report here the use of DNA variants (restriction fragment length polymorphisms) as genetic markers for zygosity determination. We have analysed the placental DNA of 22 twin pairs with known zygosity on Southern blots by hybridisation with polymorphic human DNA probes. We looked at six different polymorphic sites using four restriction enzymes and six DNA probes. Among 10 dizygotic (DZ) pairs, only one was not demonstrably different and seven had at least two discordances. Within each of the 12 monozygotic (MZ) pairs there was copyright. complete concordance. Thus, nine of 10 dizygotic and 12 of 12 monozygotic twins were assigned their correct zygosity solely by comparison of six DNA variants. The use of these highly polymorphic DNA probes may have practical importance for antenatal diagnosis and paternity testing.
    [Show full text]