Roles of the Y chromosome genes in human cancers.
Tatsuo Kido,Yun-Fai Chris Lau +1 more
TLDR
This review highlights the involvement of selected Y chromosome genes in cancer development in men, and suggests that the Y-linked genes are involved in male health and diseases in more frequently than expected.Abstract:
Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition) with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT), such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.read more
Citations
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Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
Jennifer F. Hughes,Helen Skaletsky,Laura G. Brown,Tatyana Pyntikova,Ting-Jan Cho,Natalia Koutseva,Sara Zaghlul,Tina Graves,Susie Rock,Colin Kremitzki,Robert S. Fulton,Shannon Dugan,Yan Ding,Donna Morton,Ziad Khan,Lora Lewis,Christian J. Buhay,Qiaoyan Wang,Jennifer Watt,Michael Holder,Sandy Lee,Lynne V. Nazareth,Jessica Alföldi,Steve Rozen,Donna M. Muzny,Wesley C. Warren,Richard A. Gibbs,Rick K. Wilson,Daniel W. Bellott,David C. Page +29 more
TL;DR: This article reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes, and concluded that the gene content of Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability.
Journal ArticleDOI
Functional coherence of the human y chromosome
Bruce T. Lahn,David C. Page +1 more
TL;DR: A systematic search of the nonrecombining region of the human Y chromosome (NRY) identified 12 novel genes or families, 10 with full-length complementary DNA sequences, which may account for infertility among men with Y deletions.
Journal ArticleDOI
Sexual dimorphism in cancer.
TL;DR: This Opinion article focuses on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism.
Journal ArticleDOI
Genetics of the human Y chromosome and its association with male infertility
Stacy Colaco,Deepak Modi +1 more
TL;DR: Screening for Yq microdeletions would aid the clinician in determining the cause of male infertility and decide a rational management strategy for the patient, as these deletions are transmitted to 100% of male offspring born through assisted reproduction, testing of Yq deletions will allow the couples to make an informed choice regarding the perpetuation ofmale infertility in future generations.
Journal ArticleDOI
Spermatogenic failure and the Y chromosome
Csilla Krausz,Elena Casamonti +1 more
TL;DR: The Y chromosome harbors a number of genes essential for testis development and function and is responsible for Y-linked copy-number variations (CNVs) with clinical relevance and in certain populations, the Y background may play a role in the phenotypic expression of partial AZFc rearrangements and similarly it may affect the predisposition to specific deleting events.
References
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Journal ArticleDOI
A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif
Andrew H. Sinclair,Berta P,Berta P,M. S. Palmer,Hawkins,B. Griffiths,Smith Mj,Foster Jw,Foster Jw,A.-M. Frischauf,Robin Lovell-Badge,Peter N. Goodfellow +11 more
TL;DR: A search of a 35-kilobase region of the human Y chromosome necessary for male sex determination has resulted in the identification of a new gene, termed SRY (for sex-determining region Y) and proposed to be a candidate for the elusive testis-d determining gene, TDF.
Journal ArticleDOI
Male development of chromosomally female mice transgenic for Sry
TL;DR: It is shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
Journal ArticleDOI
The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes.
Helen Skaletsky,Tomoko Kuroda-Kawaguchi,Patrick Minx,Holland S. Cordum,LaDeana W. Hillier,Laura G. Brown,Sjoerd Repping,Tatyana Pyntikova,Johar Ali,Tamberlyn Bieri,Asif T. Chinwalla,Andrew Delehaunty,Kim D. Delehaunty,Hui Du,Ginger A. Fewell,Lucinda Fulton,Robert S. Fulton,Tina Graves,Shunfang Hou,Philip Latrielle,Shawn Leonard,Elaine R. Mardis,Rachel Maupin,John Douglas Mcpherson,Tracie L. Miner,William E. Nash,Christine Nguyen,Philip Ozersky,Kymberlie H. Pepin,Susan M. Rock,Tracy Rohlfing,Kelsi Scott,Brian Schultz,Cindy Strong,Aye Mon Tin-Wollam,Shiaw-Pyng Yang,Robert H. Waterston,Richard K. Wilson,Steve Rozen,David C. Page +39 more
TL;DR: The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length, and is a mosaic of heterochromatic sequences and three classes of euchromatics sequences: X-transposed, X-degenerate and ampliconic.
Journal ArticleDOI
Four Evolutionary Strata on the Human X Chromosome
Bruce T. Lahn,David C. Page +1 more
TL;DR: The ages of individual X-Y gene pairs and the locations of their X members on the X chromosome were found to be highly correlated and age decreased in stepwise fashion from thedistal long arm to the distal short arm in at least four "evolutionary strata".
Journal ArticleDOI
Sex differences in autism spectrum disorders.
TL;DR: This review explores the current status of epidemiological, genetic, and neuroendocrinological work addressing ASD prevalence and liability in males and females so as to frame the major issues necessary to pursue a more complete understanding of the biological basis for sex-differential risk.
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Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
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