Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations

oleh: Elvis Twumasi Aboagye, Samuel Mawuli Adadey, Kevin Esoh, Mario Jonas, Carmen de Kock, Lucas Amenga-Etego, Gordon A. Awandare, Ambroise Wonkam

Format: Article
Diterbitkan: MDPI AG 2022-03-01

Deskripsi

Gap junction protein beta 2 (<i>GJB2</i>) (connexin 26) variants are commonly implicated in non-syndromic hearing impairment (NSHI). In Ghana, the <i>GJB2</i> variant p.(Arg143Trp) is the largest contributor to NSHI and has a reported prevalence of 25.9% in affected multiplex families. To date, in the African continent, <i>GJB2</i>-p.(Arg143Trp) has only been reported in Ghana. Using whole-exome sequencing data from 32 individuals from 16 families segregating NSHI, and 38 unrelated hearing controls with the same ethnolinguistic background, we investigated the date and origin of p.(Arg143Trp) in Ghana using linked markers. With a Bayesian linkage disequilibrium gene mapping method, we estimated <i>GJB2</i>-p.(Arg143Trp) to have originated about 9625 years (385 generations) ago in Ghana. A haplotype analysis comparing data extracted from Ghanaians and those from the 1000 Genomes project revealed that <i>GJB2</i>-p.(Arg143Trp) is carried on different haplotype backgrounds in Ghanaian and Japanese populations, as well as among populations of European ancestry, lending further support to the multiple independent origins of the variant. In addition, we found substantial haplotype conservation in the genetic background of Ghanaian individuals with biallelic <i>GJB2</i>-p.(Arg143Trp) compared to the <i>GJB2</i>-p.(Arg143Trp)-negative group with normal hearing from Ghana, suggesting a strong evolutionary constraint in this genomic region in Ghanaian populations that are homozygous for <i>GJB2</i>-p.(Arg143Trp). The present study evaluates the age of <i>GJB2</i>-p.(Arg143Trp) at 9625 years and supports the multiple independent origins of this variant in the global population.