A de novo paradigm for male infertility.

ABSTRACT: 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 analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10^-5) in infertile men compared to controls. Additionally, we detected a significant increase in predi

SUBMITTER: Oud MS 

PROVIDER: S-EPMC8748898 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature