Journal ArticleDOI
Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection.
Sjoerd Repping,Helen Skaletsky,Laura G. Brown,Saskia K.M. van Daalen,Cindy M. Korver,Tatyana Pyntikova,Tomoko Kuroda-Kawaguchi,Tomoko Kuroda-Kawaguchi,Jan W.A de Vries,Robert D. Oates,Sherman J. Silber,Fulco van der Veen,David C. Page,Steve Rozen +13 more
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TLDR
It is suggested that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate newgr/gr deletions.Abstract:
Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.read more
Citations
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Journal ArticleDOI
Structural variation in the human genome
TL;DR: Rapidly accumulating evidence indicates that structural variants can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
Journal ArticleDOI
The biology of infertility: research advances and clinical challenges
Martin M. Matzuk,Dolores J. Lamb +1 more
TL;DR: The past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility, but translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples.
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Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility
Niels E. Skakkebæk,Ewa Rajpert-De Meyts,Germaine M. Buck Louis,Jorma Toppari,Anna-Maria Andersson,Michael L. Eisenberg,Tina Kold Jensen,Niels Jørgensen,Shanna H. Swan,Katherine J. Sapra,Søren Ziebe,Lærke Priskorn,Anders Juul +12 more
TL;DR: There is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations, because environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends.
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Genetics of male infertility.
TL;DR: Large, international, and consortium-based whole-exome and whole-genome studies are the most promising approach for the discovery of the missing genetic aetiology of idiopathic male infertility.
Eaa/emqn best practice guidelines for molecular diagnosis of y chromosomal microdeletions
Manuela Simoni,Egbert Bakker +1 more
TL;DR: In the light of the recent advance in the knowledge of the Y chromosome sequence and of the mechanism of microdeletion it was agreed that the basic 1999 protocol, based on two multiplex polymerase chain reactions each covering the three AZF regions, is still fully valid and appropriate for accurate diagnosis.
References
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Journal ArticleDOI
Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure.
Sjoerd Repping,Sjoerd Repping,Helen Skaletsky,Julian Lange,Sherman J. Silber,Fulco van der Veen,Robert D. Oates,David C. Page,Steve Rozen +8 more
TL;DR: The discovery of breakpoint hotspots suggest that factors in addition to homology underlie these deletions, which are the largest of all human interstitial deletions for which deletion junctions and complete intervening sequence are available.
Journal ArticleDOI
Recent common ancestry of human Y chromosomes: Evidence from DNA sequence data
TL;DR: It is estimated that the spread of Y chromosomes out of Africa is much more recent than previously was thought, and the data indicate substantial population growth in the effective number of human Y chromosomes.
Journal ArticleDOI
Hierarchical Patterns of Global Human Y-Chromosome Diversity
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TL;DR: A nested cladistic analysis (NCA) demonstrated that both population structure processes (recurrent gene flow restricted by isolation by distance and long-distance dispersals) and population history events were instrumental in explaining this tripartite division of global NRY diversity.
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