DOCSLIB.ORG

The Endless Quest for Sex Determination Genes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Endless Quest for Sex Determination Genes Clin Genet 2004: 67: 15–25 Copyright # Blackwell Munksgaard 2004 Printed in Singapore. All rights reserved CLINICAL GENETICS doi: 10.1111/j.1399-0004.2004.00376.x Developmental Biology The endless quest for sex determination genes a a,b,c Fleming A, Vilain E. The endless quest for sex determination genes. A Fleming and E Vilain Clin Genet 2004: 67: 15–25. # Blackwell Munksgaard, 2004 aDepartment of Human Genetics, bDepartment of Pediatrics, and Disorders in human sex determination cause defects in gonadal function cDepartment of Urology, David Geffen and can result in a spectrum of abnormalities in the internal and external School of Medicine at UCLA, Los genitalia, ranging from relatively mild sexual ambiguities to complete Angeles, CA, USA sex reversal. Several genes involved in sex determination have been Key words: sex determination – gonadal validated in humans, and activities of their gene products are being dysgenesis – gonads – development – elucidated, particularly in mouse models. However, how these genes sexual ambiguity – genetics interact in an overall process remains far from clear, and it is probable Corresponding author: Eric Vilain, MD, that many additional genes are involved. Management of patients with PhD, Departments of Human Genetics pathologies in sex determination and subsequent differentiation is and Pediatrics, UCLA School of currently under debate, but will require not only an understanding of the Medicine, Gonda Center, Suite 6357, 695 multiple definitions of an individual’s sex but also an increased Charles Young Drive South, Los Angeles, knowledge of the molecular mechanisms involved in sex determination. CA 90095-7088, USA. Tel.: þ1 310 267 2455; fax: þ1 310 794 5446; e-mail: [email protected] Received 23 September 2004, revised and accepted for publication 23 September 2004 Defining an individual’s sex is not simple. Geno- regress and Mu¨llerian ducts become the upper typic sex refers to genetic make-up, where males part of the vagina, uterus, and Fallopian tubes. (typically 46,XY) or females (46,XX) are defined Pathologies of sexual development are quite by presence or absence of a Y chromosome (1). varied in humans. Sex differentiation pathologies Phenotypic sex is characterized by the primary and are relatively common (about one in 100) and secondary sex characteristics of an individual. Sex- better understood than those of sex determin- ual identity includes a person’s sense of self (gender ation. Here, gonads develop normally, but defects identity) and his/her attraction to others. These in subsequent gene and/or hormone function aspects of sex are not always in concordance in a result in abnormalities of the internal or external given individual, and consideration of all three genitalia, with a wide range of type and severity. aspects is critical and complex – and currently the These abnormalities are usually variations on the subject of much debate – in the clinical setting. norm, such as a small penis, undescended testes Physiological sexual development includes both (cryptorchidism), an enlarged clitoris, or abnor- sex determination and sex differentiation, a some- mal positioning of the urethral opening (hypo- what arbitrary but useful distinction. In mam- spadias). Some, however, are severe enough to mals, gonads are indistinguishable (indifferent) be termed sexual ambiguities. early in their development; sex determination – Sex determination pathologies are compara- the decision to develop as testes or ovaries – tively rare (estimated at one in 20,000). They begins midway through gonadogenesis and ends result from duplications, mutations, or deletions with formation of the gonads. Sex differentiation of sex-determining genes and involve abnormal follows in accordance: in males, testicular hor- gonadal development (dysgenesis) and, typically, mones cause the regression of Mu¨llerian ducts a discrepancy between genotypic and phenotypic and development of Wolffian ducts into the epi- sex. XX males often have small, azoospermic didymis, vas deferens and seminiferous tubules, testes, normal male genitalia, and no Mu¨llerian- and testicular descent; in females, Wolffian ducts derived structures, but can also have hypospadias 15 Fleming and Vilain or sexual ambiguity. XX true hermaphrodites have default state must have a molecular basis has gonads with both testicular and ovarian tissue, spurred research to explore female mechanisms ambiguous genitalia with persistence of some as well. Finally, because clinical management Mu¨llerian structures. XY females with complete does not always fall easily into the categories out- or pure gonadal dysgenesis have fibrous (streak) lined above, we also include figures (Figs 1 and 2) gonads and normal female genitalia, including a that summarize the major disorders of sexual uterus. XY females with partial dysgenesis may development, including both determination and have sexual ambiguities. Although the focus of differentiation. much research, these pathologies are not yet well understood and can be difficult to diagnose. Genes involved in testis development Here, we present information about each of SRY the genes known to be involved in human sex determination (Table 1). Although many genes Around the early 1990s, a series of elegant experi- involved in sex determination have been identi- ments found SRY to be the once elusive mamma- fied in animal models, their functions are not yet lian testis-determining gene. Positional cloning fully understood, and the majority of those genes located a 35-kb fragment of the Y chromosome have not been validated in humans. Male- translocated onto the X chromosome of XX male determining genes have been more thoroughly and true hermaphrodite patients (3, 4); sequence studied to date, perhaps an outgrowth of Jost’s analysis and gene mapping defined a conserved experiments in the 1940s (2) that showed testis sequence – SRY – within that fragment (5, 6). determination to be synonymous with sex deter- Murine Sry gene expression profiles revealed a mination, leaving ovarian determination to be the male-specific increase in transcript consistent default state. Recently, understanding that even a with earliest divergence of male and female Table 1. Known genes involved in sex determination (2, 3) Validated Gain-of-function Gene in humans Human locus Putative function Loss-of-function phenotype phenotype Testis determining SRY X Yp11.3 Transcription factor XY female (human, mouse) XX male (human, mouse) SOX9 X 17q24 Transcription factor XY female þ campomelic XX male dysplasia (human) (human, mouse) SF1 X 9q33 Transcription factor XY female þ adrenal insufficiency (human); genital and adrenal developmental blockage (KO) WT1 X 11p13 Transcription factor XY female þ kidney defects, Wilms’ tumor (human); absent gonads, blockage in kidney and adrenal development (KO) DAX1 X Xp21.3 Transcription factor Adrenal hypoplasia congenita; XY female hypogonadism (human); (human, mouse) spermatogenesis block (mouse) DMRT1 X 9p24.3 Transcription factor XY female (human)a; postnatal loss of Sertoli and germ cells (KO) ATRX X Xq13.3 Transcription factor XY female þ mental retardation, a-thalassemia (human) M33 17q25 Transcription factor XY female, Sox9 reduced (KO) FGF9 13q11–13 Signaling molecule XY female (variable phenotype) þ lung defects (KO) Ovary determining WNT4 X 1p35 Signaling molecule XX testosterone XY female synthesis þ Wolffian duct (human) development (mice) FOXL2 Xb 3q23 Transcription factor Premature ovarian failure þ BPES (humans); XX male (goats) KO, mouse knock out; BPES, Blepharophimosis Ptosis Epicanthus Inversus Syndrome. aDMRT1 is one gene in a large sex-reversing deletion. bNot validated for sex reversal in humans. 16 Sex determination genes Fig. 1. Simplifieddiagnosticflowchart of the major disorders of sexual development in feminized boys. gonadal development (7, 8). XX and XYpos are not yet clear, but several factors have been (a weak allele of Sry tending to sex reverse on a implicated, including SP1, WT1, SF1, GATA4, C57BL/6 background) mice transgenic for a FOG2 (12), and three members of the insulin 14-kb fragment containing Sry developed testes receptor tyrosine kinase family (19). (9, 10). Deletions and mutations in SRY/Sry Despite certainty that SRY is the testis- often result in XY female sex reversal [in mice: determining gene, it is still not known what (11) and (6); in humans: reviewed in (12)]. downstream targets SRY regulates and whether SRY, a single-exon gene on the Y chromosome, it acts as an activator or repressor (20), although is an apparent transcription factor (13). Its gene it is widely thought to up-regulate SOX9 expres- product contains a conserved High Mobility sion. In addition, sequence analysis of SRY does Group (HMG) motif that binds and bends its not explain all pathologies of sex determination. target DNA (14) and is flanked by two nuclear Genetic studies have shown that SRY is not localization signals (NLSs) (15). Almost all sex- detected in 8% of unambiguous XX males, 91% reversing mutations in SRY are found in the of XX males with sexual ambiguities, and 84% of HMG/NLS domain (12) and affect its DNA- XX true hermaphrodites (21), and that mutations binding affinity (13), its binding/bending of target in the SRY gene have been found in only 15% of DNA (16), or its nuclear localization (17, 18). The XY females (12). These data indicate that add- precise mechanisms regulating expression of SRY itional genes are involved in testis determination. Fig. 2. Simplifieddiagnosticflowchart
Load more

Recommended publications
  • Handbook for Parents
    Contributors Cassandra L. Aspinall, MSW, LICSW Christine Feick, MSW Craniofacial Center, Seattle Children’s Hospital; Ann Arbor, MI University of Washington School of Social Work, Seattle, WA Sallie Foley, LMSW Certified Sex Therapist, AASECT; Dept. Social Arlene B. Baratz, MD Work/Sexual Health, University of Michigan Medical Advisor, Androgen Insensitivity Health Systems, Ann Arbor, MI Syndrome Support Group, Pittsburgh, PA Joel Frader, MD, MA Max & Tamara Beck General Academic Pediatrics, Children’s Atlanta, GA Memorial Hospital; Dept. Pediatrics and Program in Medical Humanities & Bioethics, William Byne, MD Feinberg School of Medicine, Northwestern Psychiatry, Mount Sinai Medical Center, New University, Chicago, IL York, NY Jane Goto David Cameron Board of Directors, Intersex Society of North Intersex Society of North America, San America; Board of Directors, Androgen Francisco, CA Insensitivity Syndrome Support Group, Seattle, Anita J. Catlin, DSNc, FNP, FAAN WA Nursing and Ethics, Sonoma State University, Michael Grant Sonoma, CA Lansing, MI Cheryl Chase Janet Green Founder and Executive Director, Intersex Society Co-Founder, Bodies Like Ours; Board of of North America, Rohnert Park, CA Directors, CARES Foundation; Board of Kimberly Chu, LCSW, DCSW Overseers, Beth Israel Hospital; Board of Department of Child & Adolescent Psychiatry, Trustees, Continuum Healthcare, New York, Mount Sinai Medical Center, New York, NY NY Howard Devore Philip A. Gruppuso, MD San Francisco, CA Associate Dean of Medical Education, Brown University; Pediatric Endocrinology, Rhode Alice Dreger, Ph.D. (Project Coordinator and Island Hospital, Providence, RI Editor) Program in Medical Humanities and Bioethics, William G. Hanley, BPS Feinberg School of Medicine, Northwestern Memphis, TN University, Chicago, IL iii iv Debora Rode Hartman Charmian A.
    [Show full text]
  • Genetics, Underlying Pathologies and Psychosexual Differentiation Valerie A
    REVIEWS DSDs: genetics, underlying pathologies and psychosexual differentiation Valerie A. Arboleda, David E. Sandberg and Eric Vilain Abstract | Mammalian sex determination is the unique process whereby a single organ, the bipotential gonad, undergoes a developmental switch that promotes its differentiation into either a testis or an ovary. Disruptions of this complex genetic process during human development can manifest as disorders of sex development (DSDs). Sex development can be divided into two distinct processes: sex determination, in which the bipotential gonads form either testes or ovaries, and sex differentiation, in which the fully formed testes or ovaries secrete local and hormonal factors to drive differentiation of internal and external genitals, as well as extragonadal tissues such as the brain. DSDs can arise from a number of genetic lesions, which manifest as a spectrum of gonadal (gonadal dysgenesis to ovotestis) and genital (mild hypospadias or clitoromegaly to ambiguous genitalia) phenotypes. The physical attributes and medical implications associated with DSDs confront families of affected newborns with decisions, such as gender of rearing or genital surgery, and additional concerns, such as uncertainty over the child’s psychosexual development and personal wishes later in life. In this Review, we discuss the underlying genetics of human sex determination and focus on emerging data, genetic classification of DSDs and other considerations that surround gender development and identity in individuals with DSDs. Arboleda, V. A. et al. Nat. Rev. Endocrinol. advance online publication 5 August 2014; doi:10.1038/nrendo.2014.130 Introduction Sex development is a critical component of mammalian disrupted, which occurs primarily as a result of genetic development that provides a robust mechanism for con- mutations that interfere with either the development of tinued generation of genetic diversity within a species.
    [Show full text]
  • Lessons Learned on Data Sharing in COVID-19 Pandemic Can Inform Future Outbreak Preparedness and Response” Science & Diplomacy, Vol
    Jonathan LoTempio, D’Andre Spencer, Rebecca Yarvitz, Arthur Delot Vilain, Eric Vilain, and Emmanuèle Délot, “We Can Do Better: Lessons Learned on Data Sharing in COVID-19 Pandemic Can Inform Future Outbreak Preparedness and Response” Science & Diplomacy, Vol. 9, No. 2 (June 2020). https://www.sciencediplomacy.org/article/2020/we-can-do-better- lessons-learned-data-sharing-in-covid-19-pandemic-can-inform-future This copy is for non-commercial use only. More articles, perspectives, editorials, and letters can be found at www.sciencediplomacy.org. Science & Diplomacy is published by the Center for Science Diplomacy of the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society. We Can Do Better: Lessons Learned on Data Sharing in COVID-19 Pandemic Can Inform Future Outbreak Preparedness and Response Jonathan LoTempio, D’Andre Spencer, Rebecca Yarvitz, Arthur Delot Vilain, Eric Vilain, and Emmanuèle Délot he COVID-19 pandemic will remain a critical issue until a safe and Teffective vaccine is in global use. A strong international network exists for the systematic collection and sharing of influenza genome sequence data, which has proven extensible to COVID-19.¹ However, the robust demographic and clinical data needed to understand the progression of COVID-19 within individuals and across populations are collected by an array of local, regional, federal, and/or national agencies, with country-specific, often overlapping mandates. The networks tasked with transmitting descriptive, disaggregated data have not done so in a standardized manner; most data are made available in variable, incompatible forms, and there is no central, global hub.
    [Show full text]
  • Tissue-Specific Expression and Regulation of Sexually Dimorphic Genes in Mice
    Downloaded from genome.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Tissue-specific expression and regulation of sexually dimorphic genes in mice Xia Yang,1 Eric E. Schadt,2 Susanna Wang,3 Hui Wang,4 Arthur P. Arnold,5 Leslie Ingram-Drake,3 Thomas A. Drake,6 and Aldons J. Lusis1,3,7 1Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA; 2Rosetta Inpharmatics, LLC, a Wholly Owned Subsidiary of Merck & Co. Inc., Seattle, Washington 98109, USA; 3Department of Human Genetics, University of California, Los Angeles, California 90095, USA; 4Department of Statistics, College of Letters and Science, University of California, Los Angeles, California 90095, USA; 5Department of Physiological Science, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, California 90095, USA; 6Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA We report a comprehensive analysis of gene expression differences between sexes in multiple somatic tissues of 334 mice derived from an intercross between inbred mouse strains C57BL/6J and C3H/HeJ. The analysis of a large number of individuals provided the power to detect relatively small differences in expression between sexes, and the use of an intercross allowed analysis of the genetic control of sexually dimorphic gene expression. Microarray analysis of 23,574 transcripts revealed that the extent of sexual dimorphism in gene expression was much greater than previously recognized. Thus, thousands of genes showed sexual dimorphism in liver, adipose, and muscle, and hundreds of genes were sexually dimorphic in brain.
    [Show full text]
  • DSD Symposium
    DSD Symposium October 13-14 2006 Renaissance Parc 55 Hotel, San Francisco Presented by Intersex Society of North America and Gay and Lesbian Medical Association Contents Agenda for Change: Psychology and Clinical Management of Disorders of Sex Development in Adulthood Lih-Mei Liao PhD Report on Chicago Consensus Conference David Sandberg PhD, Cheryl Chase, and Eric Vilain PhD MD Nomenclature Change: I Am Not a Disorder Katie Baratz, Arlene Baratz MD, Eric Vilain PhD MD, and Peter Trinkl Counseling Adults William Byne MD and Nina Williams PhD How to Build a Team Barbara Neilson PhD and Melissa Parisi PhD Handbook for Parents Arlene Baratz MD DSDs and Cancer: Caring for Intersex Patients Katie Baratz Counseling Parents David Sandberg PhD, Arlene Baratz MD, and Ellen Feder PhD Setting the Research Agenda Lih-Mei Liao PhD DSD Symposium Parc 55 Hotel San Francisco October 13-14 2006 www.isna.org Introduction The Intersex Society of North America hosted the First DSD Symposium, a gathering of intersex adults, parents, and allied healthcare professionals, October 13-14, 2006, at the Renaissance Parc 55 Hotel in San Francisco. This was a chance to meet and learn from others working to improve the quality of healthcare for families with children born with Disorders of Sex Development, and for adults dealing with the many ongoing healthcare concerns that result from DSDs. The DSD Symposium was a mini-conference, held within the Gay and Lesbian Medical Association’s annual conference. Registrants to the GLMA conference (about 400 people) were welcome to attend all DSD Symposium presentations. There were about 40 people registered for the DSD Symposium alone.
    [Show full text]
  • Download the Background and Timeline Insert
    HUMAN “They’re Chasing Us Away RIGHTS from Sport” WATCH Human Rights Violations in Sex Testing of Elite Women Athletes 19301930ss 19401940s-1950s-1950s s Unsubstantiated stories of men Systematic sex testing, of a sort, exists as early as masquerading as women in international the 1940s via identity cards and “certificates of sporting events first appear.i femininity,” with the IAAF and IOC requiring all female athletes who wish to register for an event to provide a physician letter attesting to their sex for eligibility purposes.ii Meeting of the Executive Committee of the International Olympic Committee in 1951 in Vienna, chaired by IOC President Edström. © 1951 ullstein bild via Getty Images BACKGROUND You have to sacrifice so much, especially us ladies. —C.M., athlete, November 12, 2019 The regulation of women’s participation in sport via “sex testing” dates back decades. A key architect of such regulations—a former official with the International Olympic Committee (IOC) and World Athletics—later went on to characterize previous testing regimes as a “systematic violation for which the world of sport must take respon- sibility,” and “a decades-long example of sexual harassment of sexual abuse within sport [and] a flagrant abuse.”13 The earliest attempts at “sex testing” that sports authorities instituted in the 1940s for the purposes of eligibility were informal and ad hoc, but by the 1960s, sports governing bodies such as the IAAF and the IOC began system- atic mandatory testing of all women athletes based on rumors that some women “were more male than female,” resulting in “unfair competition for ‘real’ women.”14 There have never been analogous regulations for men.
    [Show full text]
  • The Genomics of Emerging Pathogens
    GG14CH13-Lipkin ARI 1 August 2013 11:16 The Genomics of Emerging Pathogens Cadhla Firth and W. Ian Lipkin Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032; email: [email protected], [email protected] Annu. Rev. Genomics Hum. Genet. 2013. Keywords 14:281–300 viruses, bacteria, emerging infectious diseases, pathogen discovery by Columbia University on 10/02/13. For personal use only. The Annual Review of Genomics and Human Genetics is online at genom.annualreviews.org Abstract This article’s doi: 10.1146/annurev-genom-091212-153446 Globalization and industrialization have dramatically altered the vulnerabil- ity of human and animal populations to emerging and reemerging infectious Copyright c 2013 by Annual Reviews. All rights reserved diseases while shifting both the scale and pace of disease outbreaks. Fortu- Annu. Rev. Genom. Human Genet. 2013.14:281-300. Downloaded from www.annualreviews.org nately, the advent of high-throughput DNA sequencing platforms has also increased the speed with which such pathogens can be detected and charac- terized as part of an outbreak response effort. It is now possible to sequence the genome of a pathogen rapidly, inexpensively, and with high sensitiv- ity, transforming the fields of diagnostics, surveillance, forensic analysis, and pathogenesis. Here, we review advances in methods for microbial discovery and characterization, as well as strategies for testing the clinical and pub- lic health significance of microbe-disease associations. Finally, we discuss how genetic data can inform our understanding of the general process of pathogen emergence. 281 GG14CH13-Lipkin ARI 1 August 2013 11:16 INTRODUCTION Infectious disease research has been transformed by the recent renaissance of the One Health approach, which recognizes the importance of the interrelationships among humans, animals, and the environment in health and disease.
    [Show full text]
  • 2020 Meeting of the Organization for the Study of Sex Differences Detailed Program
    2020 Meeting of the Organization for the Study of Sex Differences Detailed Program th Monday May 4 9:00a-5:00p Registration Open 9:30a-11:00a WORKSHOP: SABV 101 – CVD, Immune Function and Stroke Chair: Art Arnold, University of California, Los Angeles Louise McCullough, McGovern Medical School, UT Health Science Center Sex differences in stroke. Jayne Danska, Hospital for Sick Children and University of Toronto Sex differences in the immune system. Noel Bairey Merz, Cedars-Sinai Medical Center Sex and Gender differences in Cardiovascular Health and Disease: Impact on clinical care. 11:00a-1:00p Lunch on your own OR 11:00a-12:15p IGH Trainee Career Development Workshop (Open to all trainees, RSVP required, light refreshments provided) 12:00p-1:00p BSD Editorial Board Meeting (RSVP requested, lunch provided) 1:00p-2:30p Session 1: “The Role of the X Chromosome in Sex Differences in Health & Disease” Chairs: Christine Disteche, University of Washington, Rhonda Voskuhl, UCLA On the “Nature” of sex and gender research. Cara Tannenbaum, CIHR, CRIUGM X chromosome mechanisms shown in immune responses relevant to health and disease. Rhonda Voskuhl, UCLA X-inactivation escapee variation by cell and tissue type: The role in sex differences in health and disease. Christine Disteche, University of Washington Sex Chromosome Dosage Effects on Gene Expression and Chromosome Organization in Humans. Armin Raznahan, NIMH 2:30p-2:45p Coffee Break 2:45p-4:15p Session 2: “Elizabeth Young New Investigator Symposium” Chair: Jaclyn Schwarz, University of Delaware
    [Show full text]
  • Innovation Through Collaboration: Academic Annual Report 2016-2017
    Children’s Research Institute Innovation through collaboration Children’s National Health System Academic Annual Report 2016–2017 Vision Children’s National Health System aspires to be a top-five academic pediatric health system that is recognized as leading the quest to prevent or cure many of childhood’s most serious and prevalent disorders. We will achieve this vision through a unique collaboration between clinical and research programs, innovative educational programs, enhanced academic partnerships, improved infrastructure, and a stable base of financial support. Through this approach, our role as a national and international leader in the research and treatment of childhood diseases will be significantly strengthened. Contents From the Directors .............................................................................................................2 CRI Leadership .....................................................................................................................4 Major Scientific Advances 2016 ...................................................................................5 Innovation Spotlight: Gamifying E-Learning to Enhance Medical Education ............................................................................................................. 9 Leading Geneticist and Pediatrician Eric Vilain, MD, PhD, to Lead Center for Genetic Medicine Research at Children’s National Health System ...................................................................................................................
    [Show full text]
  • UNIVERSITY of CALIFORNIA Los Angeles the Effects Of
    UNIVERSITY OF CALIFORNIA Los Angeles The Effects of Chromosomal Composition and Hormonal Influences on Shaping Sex Differences in the Developing Mammalian Brain A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Human Genetics by Matthew Scott Bramble 2017 © Copyright by Matthew Scott Bramble 2017 ABSTRACT OF THE DISSERTATION The Effects of Chromosomal Composition and Hormonal Influences on Shaping Sex Differences in the Developing Mammalian Brain by Matthew Scott Bramble Doctor of Philosophy in Human Genetics University of California, Los Angeles, 2017 Professor Eric J.N. Vilain, Chair The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic brain development, we identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. RNA-sequencing identified 103 transcripts that were differentially expressed between XX and XY eNSCs at baseline (FDR=0.10). Treatment with testosterone-propionate (TP) reveals sex-specific gene expression changes, causing 2854 and 792 transcripts to become differentially expressed on XX and XY genetic backgrounds respectively. These findings indicate that testosterone exposure on XX cells have a more robust effect with regards to altering gene expression. It was also found that by exposing XX eNSCs to TP 42% (43/103) of the original 103 basal sex differences that existed became masculinized and shifted towards a XY typical gene expression pattern.
    [Show full text]
  • Lessons Learned on Data Sharing in COVID-19 Pandemic Can Inform Future Outbreak Preparedness and Response” Science & Diplomacy, Vol
    Jonathan LoTempio, D’Andre Spencer, Rebecca Yarvitz, Arthur Delot Vilain, Eric Vilain, and Emmanuèle Délot, “We Can Do Better: Lessons Learned on Data Sharing in COVID-19 Pandemic Can Inform Future Outbreak Preparedness and Response” Science & Diplomacy, Vol. 9, No. 2 (June 2020). https://www.sciencediplomacy.org/article/2020/we-can-do-better- lessons-learned-data-sharing-in-covid-19-pandemic-can-inform-future This copy is for non-commercial use only. More articles, perspectives, editorials, and letters can be found at www.sciencediplomacy.org. Science & Diplomacy is published by the Center for Science Diplomacy of the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society. We Can Do Better: Lessons Learned on Data Sharing in COVID-19 Pandemic Can Inform Future Outbreak Preparedness and Response Jonathan LoTempio, D’Andre Spencer, Rebecca Yarvitz, Arthur Delot Vilain, Eric Vilain, and Emmanuèle Délot he COVID-19 pandemic will remain a critical issue until a safe and Teffective vaccine is in global use. A strong international network exists for the systematic collection and sharing of influenza genome sequence data, which has proven extensible to COVID-19.¹ However, the robust demographic and clinical data needed to understand the progression of COVID-19 within individuals and across populations are collected by an array of local, regional, federal, and/or national agencies, with country-specific, often overlapping mandates. The networks tasked with transmitting descriptive, disaggregated data have not done so in a standardized manner; most data are made available in variable, incompatible forms, and there is no central, global hub.
    [Show full text]
  • Science and Sex Testing: the Beginnings of a Female Testing Discourse
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 12-2-2020 2:30 PM Science and Sex Testing: The Beginnings of a Female Testing Discourse Camille M. Croteau, The University of Western Ontario Supervisor: Dr. Angela Schneider, The University of Western Ontario A thesis submitted in partial fulfillment of the equirr ements for the Doctor of Philosophy degree in Kinesiology © Camille M. Croteau 2020 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Gender and Sexuality Commons, Medicine and Health Commons, and the Sports Studies Commons Recommended Citation Croteau, Camille M., "Science and Sex Testing: The Beginnings of a Female Testing Discourse" (2020). Electronic Thesis and Dissertation Repository. 7584. https://ir.lib.uwo.ca/etd/7584 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. Abstract In the 1960s, the International Olympic Committee (IOC) sanctioned testing to verify the sex of elite female athletes. Sex tests, as they were called, did not extend to male athletes, and they have tended to rely on appearance and performance alone. Now measuring testosterone levels, the Eligibility Regulations for the Female Classification scrutinizes female athletes far more than male athletes. This dissertation contributes to the sex testing literature by investigating three under-explored avenues: the history of the sex testing sports medical literature, a medical discourse analysis of IOC documents based on the implementation of sex testing, and a critical feminist analysis of the 2019 hearing of runner Mokgadi Caster Semenya.
    [Show full text]