Application of clinical exome sequencing in sperm donor screening in China

In China, genetic testing is conducted by only a small proportion of sperm banks. Traditional sperm donor screening primarily relies on family history to exclude individuals with known genetic diseases. However, this method does not fully address the genetic risks associated with recessive and late-onset dominant disorders. This study aims to conduct genetic testing for sperm donors using high-coverage clinical exome sequencing (CES) to identify disease-causing mutations in voluntarily submitted blood samples.

Peripheral blood samples from sperm donors were collected for clinical exome sequencing (CES), which targeted the coding exons of approximately 5595 clinically relevant disease-causing genes.

Among the 391 donors, 372 (95.14%) were identified as carriers of at least one pathogenic or likely pathogenic variant, including those related to autosomal recessive, digenic recessive, and complex inheritance patterns. The carrier rate for autosomal dominant and X-linked conditions was 4.86% (19/391). On average, each donor carried 3.53 recessive genetic defects. The most frequent variants were found in UGT1 A, FLG, and GJB2. Six donors with high-frequency SMN1 exon 7-8 deletions were excluded. Ultimately, 45 donors (11.51%) were rejected, resulting in a qualification rate of 88.49%.

Clinical exome sequencing (CES) of sperm donors identified carriers of genetic conditions and excluded those with a history of dominant genetic disorders. Additionally, joint donor-recipient matching for recessive gene carriers can reduce the risk of congenital defects in offspring conceived through assisted reproduction, ensuring genetic compatibility and preventing unintended transmission of genetic disorders.