Analysis of partial Y chromosome microdeletions and NGS data in Lithuanian infertile men

Infertility is a complex pathological condition that affects the male population worldwide. Male infertility is often caused by changes in the morphology and number of spermatozoa. Many of infertility cases remain unexplained, genetic causes are being discovered, including changes in chromosomes and single genes. While Y chromosome microdeletions are the most common cause of spermatogenesis disorders, failure to identify them leads to the search for new candidate genes, de novo pathogenic genomic variants associated with male infertility using next generation sequencing. The aim of this study is to investigate genetic profile of infertile men in the Lithuanian population using candidate gene approach as well as to evaluate the significance of partial Y chromosome microdeletions. The obtained results showed that the detected partial Y chromosome (sY121, sY1192, sY153 and sY1191 markers) microdeletions in the azoospermia factor region do not explain infertility cases and require more research. After candidate-gene next generation sequencing analysis in the cohort of 18 infertile men from Lithuania, genome variants in genes DPY19L2, DCC , and MTHFR were identified for three (17%) individuals, confirming the infertility phenotype. In five (28%) of individuals variants of uncertain clinical significance were identified in BRCA1 , BRCA2 , PKD1 , CSMD1 , SBF1 , DNAH8 , and TP63 genes, which are potentially associated with male infertility. This confirms that the next generation method based on the supplemented gene candidate list is useful for the identification of genetic causes of male infertility.