Analysis of genetic variants in the exon 2 and 3 of autosomal DAZLA gene among infertile South Indian men

Abstract

Abstract Background Boule, DAZLA, and DAZ are members of the Deleted in Azoospermia family of genes, which play significant roles in gametogenesis and are important fertility factors in humans. In a few studies, deletion of the Y chromosomal DAZ cluster and single nucleotide polymorphisms in the DAZLA gene were reported to affect male fertility, although this is paradoxical because they were found in both control and fertile men. As a result, the goal of this study was to check if Y chromosomal DAZ cluster deletion and SNPs in the DAZLA gene on chromosome 3 of humans are associated to male infertility in the population. For computational analysis, different bioinformatics tools such as SIFT, PolyPhen2, Mutation Taster, FATHMM, and PROVEAN were used to analyse mutations. Results Within the studied population, we found no association between DAZ deletion and the most prevalent DAZLA SNPs A260G (rs11710967) and A386G (rs1219183446). We also discovered two new deleterious genetic variations in exon 3 of the DAZLA gene, one nonsynonymous mutation that replaced Valine with Glutamate at the 66 codon position and the other a stop gain mutation at the 74 amino acid position. These genetic changes are found in the RRM domain of the DAZLA gene, which is confirmed by Motif scan analysis and results in a change in the DAZLA protein's secondary structure. The RRM domain is a highly conserved regulatory domain for mRNA transport and translation. Azoospermia and necrospermia infertility phenotypes were shown in infertile male samples with these genotypes. Conclusion We can conclude that further investigation of the aforesaid new mutations in the DAZLA gene may be valuable in understanding their significance in male infertility in different populations due to the multifactorial nature of male infertility and arrays of gene expression required at every stage of spermatogenesis.