Open AccessTEX 11 is mutated in infertile men with azoospermia and regulates genome‐wide recombination rates in mouse
Author(s) -
Yang Fang,
Silber Sherman,
Leu N Adrian,
Oates Robert D,
Marszalek Janet D,
Skaletsky Helen,
Brown Laura G,
Rozen Steve,
Page David C,
Wang P Jeremy
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404967
Subject(s) - azoospermia , recombination , biology , genetics , genome , homologous recombination , infertility , andrology , gene , medicine , pregnancy
Genome‐wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11 , an X‐linked meiosis‐specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX 11 is mutated in infertile men with non‐obstructive azoospermia and that an analogous mutation in the mouse impairs meiosis. Genetic screening of a large cohort of idiopathic infertile men reveals that TEX 11 mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human TEX 11 missense mutations in transgenic mouse models identified one mutation (V748A) as a potential infertility allele and found two mutations non‐causative. In the mouse model, an intronless autosomal Tex11 transgene functionally substitutes for the X‐linked Tex11 gene, providing genetic evidence for the X‐to‐autosomal retrotransposition evolution phenomenon. Furthermore, we find that TEX 11 protein levels modulate genome‐wide recombination rates in both sexes. These studies indicate that TEX 11 alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans.