TEX11 is mutated in infertile men with azoospermia and regulates genome‐wide recombination rates in mouse. Issue 9 (1st July 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EMBO molecular medicine. Volume 7:Issue 9(2015:Sep.)
• Page Start: 1198
• Page End: 1210
• Publication Date: 2015-07-01
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.201404967
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="main" id="emmm201404967-abs-0001"> <title>Abstract</title> <p>Genome‐wide recombination is essential for genome stability, evolution, and speciation. Mouse <italic>Tex11</italic>, an X‐linked meiosis‐specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that <italic>TEX11</italic> 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 <italic>TEX11</italic> mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human <italic>TEX11</italic> 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 <italic>Tex11</italic> transgene functionally substitutes for the X‐linked <italic>Tex11</italic> gene, providing genetic evidence for the X‐to‐autosomal retrotransposition evolution phenomenon. Furthermore, we find that TEX11 protein levels modulate genome‐wide recombination rates in both sexes. These studies indicate that <italic>TEX11</italic> alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans.</p> </abstract>