STRC gene and STRCP1 pseudogene copy number variant analysis in a sample of Yakuts with normal hearing

Copy number variations (CNV) in the STRC gene are the main cause of autosomal recessive deafness type 16 (DFNB16, OMIM #603720). Genetic testing of DFNB16 is complicated by the complexity of the chromosomal region (15q15.3) containing a segmental duplication of five genes, including the STRC gene and its highly homologous pseudogene STRCP1. Clinically, DFNB16 is associated with a mild and moderate form of hearing loss, which, in our opinion, is due to the compensatory effect of the pseudogene, as was shown in spinal muscular atrophy. In this regard, to understand the molecular mechanisms of occurrence and clinical features of DFNB16, it is relevant to study the number of copies of not only the STRC gene, but also the STRCP1 pseudogene. In total, copy number changes in the STRC gene were detected in 7 (6.2%) individuals, and in the STRCP1 pseudogene in 16 (14.1%) individuals. It was found that these copy number changes most likely occurred as a result of unequal crossing over (STRC/STRCP1 – deletion/deletion or norm), cases associated with gene conversion (STRC/STRCP1 – deletion/duplication or vice versa duplication/deletion) were not detected. Comparative analysis of the frequency of altered copies of the STRC gene and the STRCP1 pseudogene revealed reliable differences between deletions (1.8%) and duplications (11.5%) in the STRCP1 pseudogene region (χ²=8.64, p<0.01), while in the STRC gene region, such differences were not observed (deletions – 2.6%, duplications – 3.5%, χ²=0.15, p>0.05). A decrease in the frequency of extended deletions in the STRCP1 pseudogene region in the Yakut population is probably associated with selection pressure, which indicates a possible compensatory role of the pseudogene in the absence of a functional copy of STRC.

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