Identifying potential genetic biomarkers for sperm dysfunction through whole-genome sequencing.

Area of Science:

• Genetics
• Reproductive Biology
• Genomic Medicine

Background:

• Male infertility affects nearly 50% of infertile couples globally.
• The genetic underpinnings of idiopathic male infertility remain largely unknown.
• Identifying genetic factors is crucial for diagnosis and treatment.

Purpose of the Study:

• To investigate the genomic landscape of male infertility.
• To identify novel genetic variants associated with sperm dysfunction.
• To explore the molecular basis of male infertility.

Main Methods:

• Whole-genome sequencing (WGS) was performed on men with and without infertility.
• Sanger sequencing was used for variant validation.
• Comparative genomic analysis identified variants specific to the infertility group.

Main Results:

• A higher burden of genomic variants was observed in men with sperm dysfunction infertility compared to normozoospermic controls.
• Several novel missense variants in genes like DNAJB13, MNS1, DNAH6, HYDIN, DNAH7, DNAH17, and CATSPER1 were exclusively found in infertile men.
• Likely pathogenic variants, including frameshift and nonsense mutations in DNAH2, CFAP61, and FSIP2, were identified, impacting sperm function.

Conclusions:

• Novel genetic variants are associated with male infertility, particularly affecting sperm flagellar function and motility.
• These findings provide new insights into the molecular causes of male infertility.
• The identified variants have implications for future diagnostic and therapeutic strategies in male infertility.