TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse
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 analogo...
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| Format: | Article |
| Language: | en_US |
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EMBO Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/107724 https://orcid.org/0000-0001-9920-3411 |
| _version_ | 1826202430161813504 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 |
| author_sort | Yang, Fang |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:07:21Z |
| format | Article |
| id | mit-1721.1/107724 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:07:21Z |
| publishDate | 2017 |
| publisher | EMBO Press |
| record_format | dspace |
| spelling | mit-1721.1/1077242022-10-01T08:20:27Z TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse 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 Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Page, David C 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. Howard Hughes Medical Institute (Award) National Institutes of Health (U.S.) (NIH/NIGMS grant R01GM076327) 2017-03-27T16:08:04Z 2017-03-27T16:08:04Z 2015-07 2015-06 Article http://purl.org/eprint/type/JournalArticle 1757-4676 1757-4684 http://hdl.handle.net/1721.1/107724 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. https://orcid.org/0000-0001-9920-3411 en_US http://dx.doi.org/10.15252/emmm.201404967 EMBO Molecular Medicine Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf EMBO Press European Molecular Biology Organization (EMBO) |
| spellingShingle | 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 TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse |
| title | TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse |
| title_full | TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse |
| title_fullStr | TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse |
| title_full_unstemmed | TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse |
| title_short | TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse |
| title_sort | tex11 is mutated in infertile men with azoospermia and regulates genome wide recombination rates in mouse |
| url | http://hdl.handle.net/1721.1/107724 https://orcid.org/0000-0001-9920-3411 |
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