Aboagye Elvis Twumasi, Adadey Samuel Mawuli, Esoh Kevin, Jonas Mario, de Kock Carmen, Amenga-Etego Lucas, Awandare Gordon A, Wonkam Ambroise
West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana.
Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Biology (Basel). 2022 Mar 21;11(3):476. doi: 10.3390/biology11030476.
Gap junction protein beta 2 () (connexin 26) variants are commonly implicated in non-syndromic hearing impairment (NSHI). In Ghana, the 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, -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 -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 -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 -p.(Arg143Trp) compared to the -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 -p.(Arg143Trp). The present study evaluates the age of -p.(Arg143Trp) at 9625 years and supports the multiple independent origins of this variant in the global population.
缝隙连接蛋白β2（）（连接蛋白26）变体通常与非综合征性听力损失（NSHI）有关。在加纳，p.（Arg143Trp）变体是NSHI的最大致病因素，在受影响的多重家庭中报告的患病率为25.9%。迄今为止，在非洲大陆，-p.（Arg143Trp）仅在加纳有报道。利用来自16个分离NSHI的家庭的32名个体以及38名具有相同民族语言背景的无关听力正常对照的全外显子测序数据，我们使用连锁标记研究了加纳p.（Arg143Trp）的出现时间和起源。通过贝叶斯连锁不平衡基因定位方法，我们估计-p.（Arg143Trp）大约在9625年前（385代）起源于加纳。一项单倍型分析比较了从加纳人以及千人基因组计划中提取的数据，结果显示-p.（Arg143Trp）在加纳人和日本人以及欧洲血统人群中携带于不同的单倍型背景上，这进一步支持了该变体的多个独立起源。此外，我们发现与加纳听力正常的-p.（Arg143Trp）阴性组相比，双等位基因-p.（Arg143Trp）的加纳个体的遗传背景中存在大量单倍型保守性，这表明在加纳人群中该基因组区域对于-p.（Arg143Trp）纯合子存在强烈的进化限制。本研究评估-p.（Arg143Trp）的出现时间为9625年，并支持该变体在全球人群中的多个独立起源。
