4 documents found, page 1 of 1
A de novo paradigm for male infertility
Oud, M.S.; Smits, R.M.; Smith, H.E.; Mastrorosa, F.K.; Holt, G.S.; Houston, B.J.; de Vries, P.F.; Alobaidi, B.K.S.; Batty, L.E.; Ismail, H.De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic an...
Biallelic mutations in M1AP are associated with meiotic arrest, severely impair...
Friedrich, C.; Temel, S.G.; Nagirnaja, L.; Oud, M.S.; Lopes, A.M.; van der Heijden, G.W.; Heald, J.; Rotte, N.; Heald, J.; Rotte, N.; Wistuba, J.Male infertility affects ~7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis, but so far only few validated causal genes have been reported. To address this gap, we performed whole exome sequencing in 58 men with unexplained meiotic arrest and identified in three unrelated men the same homozygous frames...
Rare double sex and mab-3-related transcription factor 1 regulatory variants in...
Lima, A.C.; Carvalho, F.; Gonçalves, J.; Fernandes, S.; Marques, P.I.; Sousa, M.; Barros, A.; Seixas, A.; Amorim, A.; Conrad, D.F.; Lopes, M.The double sex and mab-3-related transcription factor 1 (DMRT1) gene has long been linked to sex-determining pathways across vertebrates and is known to play an essential role in gonadal development and maintenance of spermatogenesis in mice. In humans, the genomic region harboring the DMRT gene cluster has been implicated in disorders of sex development and recently DMRT1 deletions were shown to be associated ...
Human spermatogenic failure purges deleterious mutation load from the autosomes...
Lopes, Alexandra; Aston, Kenneth I.; Thompson, Emma E; Carvalho, Filipa; Gonçalves, João; Huang, N.; Matthiesen, Rune; Noordam, Michiel J.Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying...