Cargando…

Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance

Deciphering the functional relationships of genes resulting from genome-wide screens for polymorphisms that are associated with phenotypic variations can be challenging. However, given the common association with certain phenotypes, a functional link should exist. We have tested this prediction in n...

Descripción completa

Detalles Bibliográficos
Autores principales: Greither, Thomas, Behre, Hermann M., Herlyn, Holger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820667/
https://www.ncbi.nlm.nih.gov/pubmed/36613967
http://dx.doi.org/10.3390/ijms24010524
_version_ 1784865517856620544
author Greither, Thomas
Behre, Hermann M.
Herlyn, Holger
author_facet Greither, Thomas
Behre, Hermann M.
Herlyn, Holger
author_sort Greither, Thomas
collection PubMed
description Deciphering the functional relationships of genes resulting from genome-wide screens for polymorphisms that are associated with phenotypic variations can be challenging. However, given the common association with certain phenotypes, a functional link should exist. We have tested this prediction in newly sequenced exomes of altogether 100 men representing different states of fertility. Fertile subjects presented with normal semen parameters and had naturally fathered offspring. In contrast, infertile probands were involuntarily childless and had reduced sperm quantity and quality. Genome-wide association study (GWAS) linked twelve non-synonymous single-nucleotide polymorphisms (SNPs) to fertility variation between both cohorts. The SNPs localized to nine genes for which previous evidence is in line with a role in male fertility maintenance: ANAPC1, CES1, FAM131C, HLA-DRB1, KMT2C, NOMO1, SAA1, SRGAP2, and SUSD2. Most of the SNPs residing in these genes imply amino acid exchanges that should only moderately affect protein functionality. In addition, proteins encoded by genes from present GWAS occupied peripheral positions in a protein–protein interaction network, the backbone of which consisted of genes listed in the Online Mendelian Inheritance in Man (OMIM) database for their implication in male infertility. Suggestive of an indirect impact on male fertility, the genes focused were indeed linked to each other, albeit mediated by other interactants. Thus, the chances of identifying a central player in male infertility by GWAS could be limited in general. Furthermore, the SNPs determined and the genes containing these might prove to have potential as biomarkers in the diagnosis of male fertility.
format Online
Article
Text
id pubmed-9820667
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98206672023-01-07 Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance Greither, Thomas Behre, Hermann M. Herlyn, Holger Int J Mol Sci Article Deciphering the functional relationships of genes resulting from genome-wide screens for polymorphisms that are associated with phenotypic variations can be challenging. However, given the common association with certain phenotypes, a functional link should exist. We have tested this prediction in newly sequenced exomes of altogether 100 men representing different states of fertility. Fertile subjects presented with normal semen parameters and had naturally fathered offspring. In contrast, infertile probands were involuntarily childless and had reduced sperm quantity and quality. Genome-wide association study (GWAS) linked twelve non-synonymous single-nucleotide polymorphisms (SNPs) to fertility variation between both cohorts. The SNPs localized to nine genes for which previous evidence is in line with a role in male fertility maintenance: ANAPC1, CES1, FAM131C, HLA-DRB1, KMT2C, NOMO1, SAA1, SRGAP2, and SUSD2. Most of the SNPs residing in these genes imply amino acid exchanges that should only moderately affect protein functionality. In addition, proteins encoded by genes from present GWAS occupied peripheral positions in a protein–protein interaction network, the backbone of which consisted of genes listed in the Online Mendelian Inheritance in Man (OMIM) database for their implication in male infertility. Suggestive of an indirect impact on male fertility, the genes focused were indeed linked to each other, albeit mediated by other interactants. Thus, the chances of identifying a central player in male infertility by GWAS could be limited in general. Furthermore, the SNPs determined and the genes containing these might prove to have potential as biomarkers in the diagnosis of male fertility. MDPI 2022-12-28 /pmc/articles/PMC9820667/ /pubmed/36613967 http://dx.doi.org/10.3390/ijms24010524 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Greither, Thomas
Behre, Hermann M.
Herlyn, Holger
Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance
title Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance
title_full Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance
title_fullStr Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance
title_full_unstemmed Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance
title_short Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance
title_sort genome-wide association screening determines peripheral players in male fertility maintenance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820667/
https://www.ncbi.nlm.nih.gov/pubmed/36613967
http://dx.doi.org/10.3390/ijms24010524
work_keys_str_mv AT greitherthomas genomewideassociationscreeningdeterminesperipheralplayersinmalefertilitymaintenance
AT behrehermannm genomewideassociationscreeningdeterminesperipheralplayersinmalefertilitymaintenance
AT herlynholger genomewideassociationscreeningdeterminesperipheralplayersinmalefertilitymaintenance