Male Infertility Knowledgebase: decoding the genetic and disease landscape.

Area of Science:

• Genetics
• Reproductive Biology
• Bioinformatics

Background:

• Male infertility affects one-third of global infertility cases, often with an unexplained genetic origin.
• Understanding the genetic basis of male infertility is crucial for diagnosis, management, and genetic counseling.
• Existing research has identified chromosomal aberrations and gene associations, but a significant portion of cases remain genetically elusive.

Purpose of the Study:

• To develop a comprehensive, manually curated knowledgebase (MIK) integrating omics data to facilitate research into the genetic etiology of male infertility.
• To provide tools for analyzing gene associations, pathways, and disease links related to male reproductive disorders.
• To identify shared genetic etiologies between male infertility and other conditions like cancer and cardiovascular diseases.

Main Methods:

• Manual curation of a repository (MIK) integrating information on approximately 17,000 genes, pathways, gene ontology, and disease associations.
• Incorporation of data on chromosomal aberrations and syndromic associations with male infertility.
• Application of gene prioritization and network analysis for identifying novel candidate genes, exemplified by cryptorchidism.

Main Results:

• The MIK database integrates extensive genetic and disease information relevant to male infertility.
• Analysis revealed shared genetic etiologies between male infertility, cancer, and other non-reproductive conditions (e.g., cardiovascular, metabolic diseases) via specific pathways like interleukin signaling.
• The knowledgebase successfully identified 149 novel candidate genes for cryptorchidism through advanced analysis.

Conclusions:

• The Male Infertility Knowledgebase (MIK) serves as a vital platform for reviewing genetic information and identifying novel candidate genes for male infertility.
• MIK aids in understanding pleiotropic genes and predicting potential future high-risk diseases associated with male infertility.
• The findings highlight shared genetic underpinnings between male infertility and other complex diseases, paving the way for integrated research and therapeutic strategies.