Genetic characterization of a missense mutation in the X-linked TAF7L gene identified in an oligozoospermic man

Autor:	Li Ling, Fangfang Li, Pinglan Yang, Robert D Oates, Sherman Silber, Cornelia Kurischko, Francis C Luca, N Adrian Leu, Jinwen Zhang, Qiuling Yue, Helen Skaletsky, Laura G Brown, Steve G Rozen, David C Page, P Jeremy Wang, Ke Zheng
Rok vydání:	2022
Předmět:	Male China Special Issue Aspartic Acid TATA-Binding Protein Associated Factors Mutation Missense Oligospermia Cell Biology General Medicine Mice Reproductive Medicine Genes X-Linked Mutation Animals Humans Transcription Factor TFIID Infertility Male
Zdroj:	Biol Reprod
ISSN:	1529-7268 0006-3363
Popis:	Although hundreds of knockout mice show infertility as a major phenotype, the causative genic mutations of male infertility in humans remain rather limited. Here, we report the identification of a missense mutation (D136G) in the X-linked TAF7L gene as a potential cause of oligozoospermia in men. The human aspartate (D136) is evolutionally conserved across species, and its change to glycine (G) is predicted to be detrimental. Genetic complementation experiments in budding yeast demonstrate that the conserved aspartate or its analogous asparagine (N) residue in yeast TAF7 is essential for cell viability and thus its mutation to G is lethal. Although the corresponding D144G substitution in the mouse Taf7l gene does not affect male fertility, RNA-seq analyses reveal alterations in transcriptomic profiles in the Taf7l (D144G) mutant testes. These results support TAF7L mutation as a risk factor for oligozoospermia in humans.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d04a0f0fbcbcc9d237e3ee33661a7f79 https://doi.org/10.1093/biolre/ioac093 Zobrazit plný text záznamu