TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse
Name
Page_TEX11 is mutated.pdf
Size
2.13 MB
Format
Adobe PDF
Checksum (MD5)
bab4c23b84482d607a82803a609692f7
Author(s)
Yang, Fang
Silber, Sherman
Leu, N. Adrian
Oates, Robert D.
Marszalek, Janet D.
Skaletsky, Helen
Brown, Laura G.
Rozen, Steve
Wang, P. Jeremy
Page, David C
Date Issued
July 2015
Journal
EMBO Molecular Medicine
Publisher
EMBO Press
Citation
Yang, Fang, Sherman Silber, N. Adrian Leu, Robert D. Oates, Janet D. Marszalek, . Skaletsky, Laura G. Brown, Steve Rozen, David C. Page, and P. Jeremy Wang. “TEX11 Is Mutated in Infertile Men with Azoospermia and Regulates Genome-Wide Recombination Rates in Mouse.” EMBO Molecular Medicine 7, no. 9 (July 1, 2015): 1198–1210.
Version
Final published version
Abstract
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 TEX11 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 TEX11 mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human TEX11 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 TEX11 protein levels modulate genome‐wide recombination rates in both sexes. These studies indicate that TEX11 alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.15252/emmm.201404967
