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Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes
- Source :
- Human Molecular Genetics. 29:2451-2459
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- Rare coding variants have been proven to be one of the significant factors contributing to spermatogenic failure in patients with non-obstructive azoospermia (NOA) and severe oligospermia (SO). To delineate the molecular characteristics of idiopathic NOA and SO, we performed whole-exome sequencing of 314 unrelated patients of Chinese Han origin and verified our findings by comparing to 400 fertile controls. We detected six pathogenic/likely pathogenic variants and four variants of unknown significance, in genes known to cause NOA/SO, and 9 of which had not been earlier reported. Additionally, we identified 20 novel NOA candidate genes affecting 25 patients. Among them, five (BRDT, CHD5, MCM9, MLH3 and ZFX) were considered as strong candidates based on the evidence obtained from murine functional studies and human single-cell (sc)RNA-sequencing data. These genetic findings provide insight into the aetiology of human NOA/SO and pave the way for further functional analysis and molecular diagnosis of male infertility.
- Subjects :
- Adult
Male
Infertility
Candidate gene
Kruppel-Like Transcription Factors
Nerve Tissue Proteins
MLH3
Biology
Male infertility
Mice
03 medical and health sciences
0302 clinical medicine
Exome Sequencing
Genetics
medicine
Animals
Humans
Genetic Predisposition to Disease
Spermatogenesis
Molecular Biology
Infertility, Male
Genetics (clinical)
Exome sequencing
Azoospermia
030304 developmental biology
0303 health sciences
Minichromosome Maintenance Proteins
DNA Helicases
Nuclear Proteins
Oligospermia
General Medicine
medicine.disease
MutL Proteins
030220 oncology & carcinogenesis
Mutation
Candidate Disease Gene
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....9d90ff341eee731a4ed91bee0aae8ade