Article,
Human Spermatogenic Failure Purges Deleterious Mutation Load from the Autosomes and Both Sex Chromosomes, including the Gene <italic>DMRT1</italic>
PLoS Genet, 9 (3): e1003349 (March 2013)
DOI: 10.1371/journal.pgen.1003349
Abstract
<title>Author Summary</title><p>Infertility is a disease that prevents the transmission of DNA from one generation to the next, and consequently it has been difficult to study the genetics of infertility using classical human genetics methods. Now, new technologies for screening entire genomes for rare and patient-specific mutations are revolutionizing our understanding of reproductively lethal diseases. Here, we apply techniques for variation discovery to study a condition called azoospermia, the failure to produce sperm. Large deletions of the Y chromosome are the primary known genetic risk factor for azoospermia, and genetic testing for these deletions is part of the standard treatment for this condition. We have screened over 300 men with azoospermia for rare deletions and duplications, and find an enrichment of these mutations throughout the genome compared to unaffected men. Our results indicate that sperm production is affected by mutations beyond the Y chromosome and will motivate whole-genome analyses of larger numbers of men with impaired spermatogenesis. Our finding of an enrichment of rare deleterious mutations in men with poor sperm production also raises the possibility that the slightly increased rate of birth defects reported in children conceived by <italic>in vitro</italic> fertilization may have a genetic basis.</p>
