Abstract
The mutations in the GJB2 gene are known to be a major cause of autosomal recessive deafness 1A (OMIM 220290). The most common pathogenic variants of the GJB2 gene have high ethno-geographic specificity in their distribution that being attributed to a founder effect related with Neolithic migration routes of Homo sapiens. Curiously, the c.-23+1G>A splice site variant is frequently found among deaf patients of both Caucasian and Asian origin. It is currently unknown whether this mutation did spread across Eurasia as a result of the founder effect or it could have multiple local centers of origin. To determine the origin of the c.-23+1G>A we reconstructed 𝑓2-haplotypes by genotyping SNPs on the Illumina OmniExpress 730K platform in 23 deaf individuals homozygous for this variant from different populations of Eurasia (Yakuts, Tuvinians, Evenk, Kumyk, Armenian, Russians and Slovak). The analysis revealed that the homozygosity regions in different individuals overlapped in one short region with the length of ~5.2 kb. These data support the hypothesis of the common founder effect in distribution of the c.-23+1G>A variant of GJB2 gene. Based on the published data on the c.-23+1G>A prevalence among 16,177 deaf people and calculation of TMRCA of the 𝑓2-haplotypes carrying this variant we reconstructed the potential migration routes of the c.-23+1G>A carriers around the world. This analysis indicates that the c.-23+1G>A variant may have originated approximately 6,000 years ago in the territory of the Caucasus or Middle East, followed by spread throughout Europe, South and Central Asia and other regions of the world.
Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect