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

• Published in: Biology of reproduction Vol. 107; no. 1; pp. 157 - 167
• Main Authors: Ling, Li, Li, Fangfang, Yang, Pinglan, Oates, Robert D., Silber, Sherman, Kurischko, Cornelia, Luca, Francis C., Leu, N. Adrian, Zhang, Jinwen, Yue, Qiuling, Skaletsky, Helen, Brown, Laura G., Rozen, Steve G., Page, David C., Wang, P. Jeremy, Zheng, Ke
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 25.07.2022; Oxford University Press
• Subjects: Animals; Asparagine; Aspartic Acid; Cell viability; Characterization of missense mutation in TAF7L gene; China Special Issue; Complementation; Genes, X-Linked - genetics; Humans; Infertility; Infertility, Male - genetics; Male; Mens health; Mice; Missense mutation; Mutation; Mutation, Missense; Oligospermia - genetics; Oligozoospermia; Phenotypes; Risk factors; spermatogenesis; TAF7L; TATA-Binding Protein Associated Factors - genetics; transcription factor; Transcription Factor TFIID - genetics; Transcriptomics; X chromosome; TAF7L; transcription factor; Characterization of missense mutation in TAF7L gene; oligozoospermia; X chromosome; spermatogenesis; infertility
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioac093

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. Summary Sentence A sequencing screen of infertile men identifies a missense mutation in the human TAF7L gene.