Male infertility is a multifactorial condition that contributes to around one-third of cases of infertility worldwide. Several chromosomal aberrations, single-gene and polygenic associations with male factor defects have been reported. These defects manifest as sperm number or sperm quality defects leading to infertility. However, in almost 40% of cases, the genetic etiology of male infertility remains unexplained. Understanding the causal genetic factors is crucial for effective patient management and counseling. Integrating the vast amount of available omics data on male infertility is a first step towards understanding, delineating and prioritizing genes associated with the different male reproductive disorders. The Male Infertility Knowledgebase (MIK) is a manually curated repository developed to boost research on the elusive genetic etiology of male infertility. It integrates information on ∼17 000 genes, their associated pathways, gene ontology, diseases and gene and sequence-based analysis tools. In addition, it also incorporates information on reported chromosomal aberrations and syndromic associations with male infertility. Disease enrichment of genes in MIK indicate a shared genetic etiology between cancer, male and female infertility disorders. While the genes involved in cancer pathways were found to be common causal factors for sperm number and sperm quality defects, the interleukin pathways were found to be shared and enriched between male factor defects and non-reproductive conditions like cardiovascular diseases, metabolic diseases, etc. Disease information in MIK can be explored further to identify high-risk conditions associated with male infertility and delineate shared genetic etiology. Utility of the knowledgebase in predicting novel genes is illustrated by identification of 149 novel candidates for cryptorchidism using gene prioritization and network analysis. MIK will serve as a platform for review of genetic information on male infertility, identification pleiotropic genes, prediction of novel candidate genes for the different male infertility diseases and for portending future high-risk diseases associated with male infertility.

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男性不育知识库：解码遗传和疾病格局

男性不育症是一种多因素疾病，导致全球约三分之一的不孕症病例。已经报道了几种染色体畸变、单基因和多基因与男性因素缺陷的关联。这些缺陷表现为精子数量或精子质量缺陷导致不育。然而，在几乎 40% 的病例中，男性不育的遗传病因仍然无法解释。了解因果遗传因素对于有效的患者管理和咨询至关重要。整合大量关于男性不育症的可用组学数据是了解、描绘和优先考虑与不同男性生殖障碍相关的基因的第一步。男性不育知识库 (MIK) 是一个人工管理的知识库，旨在促进对男性不育的难以捉摸的遗传病因学的研究。它整合了约 17 000 个基因、它们的相关通路、基因本体、疾病以及基于基因和序列的分析工具的信息。此外，它还包含有关报告的染色体畸变和与男性不育症相关的信息。MIK 中基因的疾病富集表明癌症、男性和女性不育症之间存在共同的遗传病因。虽然发现参与癌症通路的基因是精子数量和精子质量缺陷的常见原因，但发现白细胞介素通路在男性因素缺陷和心血管疾病、代谢疾病等非生殖疾病之间共享和富集。可以进一步探索 MIK 中的疾病信息，以识别与男性不育相关的高风险疾病，并描绘出共同的遗传病因。知识库在预测新基因中的效用通过使用基因优先级和网络分析识别 149 个新的隐睾症候选者来说明。MIK 将作为一个平台，用于审查男性不育症的遗传信息、鉴定多效性基因、预测不同男性不育症的新候选基因以及预示未来与男性不育症相关的高危疾病。知识库在预测新基因中的效用通过使用基因优先级和网络分析识别 149 个新的隐睾症候选者来说明。MIK 将作为一个平台，用于审查男性不育症的遗传信息、鉴定多效性基因、预测不同男性不育症的新候选基因以及预示未来与男性不育症相关的高危疾病。知识库在预测新基因中的效用通过使用基因优先级和网络分析识别 149 个新的隐睾症候选者来说明。MIK 将作为一个平台，用于审查男性不育症的遗传信息、鉴定多效性基因、预测不同男性不育症的新候选基因以及预示未来与男性不育症相关的高危疾病。