Genetic characterization of a missense mutation in the X-linked TAF7L gene identified in an oligozoospermic man.
Biol Reprod
; 107(1): 157-167, 2022 07 25.
Article
in En
| MEDLINE
| ID: mdl-35554494
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligospermia
/
TATA-Binding Protein Associated Factors
/
Transcription Factor TFIID
/
Infertility, Male
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Biol Reprod
Year:
2022
Document type:
Article
Affiliation country:
China