The potential impact of tumor suppressor genes on human gametogenesis: a case-control study

Hershlag, A., Peyser, A., Bristow, S. L., Puig, O., Pollock, A., Niknazar, M., Mills, A. A. (December 2019) The potential impact of tumor suppressor genes on human gametogenesis: a case-control study. J Assist Reprod Genet. ISSN 1058-0468

URL: https://www.ncbi.nlm.nih.gov/pubmed/31792669
DOI: 10.1007/s10815-019-01634-3

Abstract

PURPOSE: To study the incidence of tumor suppressor gene (TSG) mutations in men and women with impaired gametogenesis. METHODS: Gene association analyses were performed on blood samples in two distinct patient populations: males with idiopathic male infertility and females with unexplained diminished ovarian reserve (DOR). The male study group consisted of men with idiopathic azoospermia, oligozoospermia, asthenozoospermia, or teratozoospermia. Age-matched controls were men with normal semen analyses. The female study group consisted of women with unexplained DOR with anti-Mullerian hormone levels </= 1.1 ng/mL. Controls were age-matched women with normal ovarian reserve (> 1.1 ng/mL). RESULTS: Fifty-seven male cases (mean age = 38.4; mean sperm count = 15.7 +/- 12.1; mean motility = 38.2 +/- 24.7) and 37 age-matched controls (mean age = 38.0; mean sperm count = 89.6 +/- 37.5; mean motility = 56.2 +/- 14.3) were compared. Variants observed in CHD5 were found to be enriched in the study group (p = 0.000107). The incidence of CHD5 mutation c.*3198_*3199insT in the 3'UTR (rs538186680) was significantly higher in cases compared to controls (p = 0.0255). 72 DOR cases (mean age = 38.7; mean AMH = 0.5 +/- 0.3; mean FSH = 11.7 +/- 12.5) and 48 age-matched controls (mean age = 37.6; mean AMH = 4.1 +/- 3.0; mean FSH = 7.1 +/- 2.2) were compared. Mutations in CHD5 (c.-140A>C), RB1 (c.1422-18delT, rs70651121), and TP53 (c.376-161A>G, rs75821853) were found at significantly higher frequencies in DOR cases compared to controls (p </= 0.05). In addition, 363 variants detected in the DOR patients were not present in the control group. CONCLUSION: Unexplained impaired gametogenesis in both males and females may be associated with genetic variation in TSGs. TSGs, which play cardinal roles in cell-cycle control, might also be critical for normal spermatogenesis and oogenesis. If validated in larger prospective studies, it is possible that TSGs provide an etiological basis for some patients with impaired gametogenesis.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > helicase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Inheritance Program
CSHL labs > Mills lab
CSHL Cancer Center Program
Depositing User: Adrian Gomez
Date: 2 December 2019
Date Deposited: 18 Dec 2019 18:07
Last Modified: 13 Feb 2024 21:21
PMCID: PMC7056797
URI: https://repository.cshl.edu/id/eprint/38784

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