不育候选基因：基于细胞遗传学分析的计算机研究。

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

机构信息

Department of Human Genetics, Cytogenetics Laboratory, Guru Nanak Dev University (GNDU), Amritsar, Punjab, 143005, India.

出版信息

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

DOI:10.1186/s12920-022-01320-x

PMID:35918717

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9347124/

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.

摘要

背景

在未能自然受孕的育龄夫妇中，仍有很大一部分夫妇不孕的原因不明。染色体异常已被确定为男性和女性不孕的主要遗传原因之一。结构染色体异常可能会破坏各种基因的功能，其中一些基因可能对生育能力很重要。本研究旨在通过对不孕患者外周血淋巴细胞进行培养并进行 GTG 带型分析，利用 Cytoscape v3.8.2 和 Metascape 进行生物信息学分析，鉴定男性和女性不育患者的候选基因和潜在功能互作网络。

方法

对 201 例不孕患者（男性 100 例，女性 101 例）和 201 例年龄和性别匹配的健康对照者（男性 100 例，女性 101 例）进行外周血淋巴细胞培养 72 小时后行核型分析，然后进行 Cytoscape v3.8.2 和 Metascape 生物信息学分析。

结果

在不孕男性（5q2、10q2 和 17q2）和女性（6q2、16q2 和 Xq2）中发现了一些染色体区域的结构异常频率显著升高。根据原发性不孕与继发性不孕对患者进行分类，发现仅在原发性不孕的男性（5q2、17q2）和女性（16q2）中存在染色体区域的结构异常频率显著升高。Cytoscape 确定了两个与这些区域相关的特定网络：一个是男性特异性网络，包含 99 个基因，另一个是女性特异性网络，包含 109 个基因。男性和女性不育网络中富集的 GO 术语分别为“骨骼系统形态发生”和“mRNA 运输”。PSME3、PSMD3 和 CDC27 是男性不育网络中鉴定出的前 3 个枢纽基因。同样，UPF3B、IRF8 和 PSMB1 是女性不育网络中鉴定出的前 3 个枢纽基因。在男性和女性特异性网络中鉴定出的枢纽基因中，PSMB1、PSMD3 和 PSME3 是蛋白酶体复合物的功能成分。这些枢纽基因在其各自在维持小鼠模型和人类生育能力方面的作用方面仅有少量报道，需要在进一步的研究中进行验证。