Male reproductive function and the human Y chromosome: is selection acting on the Y?
The human Y chromosome encodes genes that are essential for male sex determination, spermatogenesis and protection against Turner stigmata. In recent years mutations have been identified in Y-chromosome genes associated with these phenotypes and a series of microdeletions of the long arm of the Y have been defined that are specifically associated with male infertility. In parallel, the discovery of polymorphic markers on the Y, comprising of both slow-mutating binary markers and rapidly-mutating microsatellites, has enabled the high resolution definition of a large number of paternal lineages (haplogroups). These Y-chromosome haplogroups have been extensively used to trace population movements and understand human origins and histories, but recently a growing number of association studies have been performed aimed at assessing the relationship between the Y-chromosome background and Y-linked phenotypes such as infertility and male-specific cancers. These preliminary studies, comparing haplogroup distributions between case and control populations, are promising and suggest an association between different Y-chromosome lineages, sperm counts and prostate cancer. However, we highlight the need to extend these studies to other world populations. Increased sample numbers and a better haplogroup resolution using additional binary markers in association studies are necessary. By these approaches novel associations between Y-chromosome haplotypes and disease may be revealed and the degree to which selection is acting on the human Y chromosome may be determined
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