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. 2022 Aug 2;15(1):170.
doi: 10.1186/s12920-022-01320-x.

Candidate genes for infertility: an in-silico study based on cytogenetic analysis

Jatinder Singh Sahota  1 , Bhavna Sharma  1 , Kamlesh Guleria  1 , Vasudha Sambyal  2
Affiliations

Candidate genes for infertility: an in-silico study based on cytogenetic analysis

Jatinder Singh Sahota et al. BMC Med Genomics. .

Abstract

Background: The cause of infertility remains unclear in a significant proportion of reproductive-age couples who fail to conceive naturally. Chromosomal aberrations have been identified as one of the main genetic causes of male and female infertility. Structural chromosomal aberrations may disrupt the functioning of various genes, some of which may be important for fertility. The present study aims to identify candidate genes and putative functional interaction networks involved in male and female infertility using cytogenetic data from cultured peripheral blood lymphocytes of infertile patients.

Methods: Karyotypic analyses was done in 201 infertile patients (100 males and 101 females) and 201 age and gender matched healthy controls (100 males and 101 females) after 72 h peripheral lymphocyte culturing and GTG banding, followed by bioinformatic analysis using Cytoscape v3.8.2 and Metascape.

Results: Several chromosomal regions with a significantly higher frequency of structural aberrations were identified in the infertile males (5q2, 10q2, and 17q2) and females (6q2, 16q2, and Xq2). Segregation of the patients based on type of infertility (primary v/s secondary infertility) led to the identification of chromosomal regions with a significantly higher frequency of structural aberrations exclusively within the infertile males (5q2, 17q2) and females (16q2) with primary infertility. Cytoscape identified two networks specific to these regions: a male specific network with 99 genes and a female specific network with 109 genes. The top enriched GO terms within the male and female infertility networks were "skeletal system morphogenesis" and "mRNA transport" respectively. PSME3, PSMD3, and CDC27 were the top 3 hub genes identified within the male infertility network. Similarly, UPF3B, IRF8, and PSMB1 were the top 3 hub genes identified with the female infertility network. Among the hub genes identified in the male- and female-specific networks, PSMB1, PSMD3, and PSME3 are functional components of the proteasome complex. These hub genes have a limited number of reports related to their respective roles in maintenance of fertility in mice model and humans and require validation in further studies.

Conclusion: The candidate genes predicted in the present study can serve as targets for future research on infertility.

Keywords: Female infertility; In-silico; Karyotyping; Male infertility; Network analysis; Protein–protein interaction.

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Conflict of interest statement

Corresponding author, Vasudha Sambyal and co-author, Kamlesh Guleria are Associate Editors of the journal BMC Medical Genomics. Rest of the authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Biological interaction network generated using Cytoscape v3.8.2 for the male infertility dataset
Fig. 2
Fig. 2
Biological interaction network generated using Cytoscape v3.8.2 for the female infertility dataset
Fig. 3
Fig. 3
A list of the top 20 enriched gene ontology categories identified by Metascape for the male infertility dataset
Fig. 4
Fig. 4
A list of the top 20 enriched gene ontology categories identified by Metascape for the female infertility dataset
See this image and copyright information in PMC

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