Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations
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...
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MDPI AG
2022-03-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/11/3/476 |
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| author | Elvis Twumasi Aboagye Samuel Mawuli Adadey Kevin Esoh Mario Jonas Carmen de Kock Lucas Amenga-Etego Gordon A. Awandare Ambroise Wonkam |
| author_facet | Elvis Twumasi Aboagye Samuel Mawuli Adadey Kevin Esoh Mario Jonas Carmen de Kock Lucas Amenga-Etego Gordon A. Awandare Ambroise Wonkam |
| author_sort | Elvis Twumasi Aboagye |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T13:48:57Z |
| format | Article |
| id | doaj.art-48277725a2b240b086e2f01f96c1e1dd |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T13:48:57Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
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| series | Biology |
| spelling | doaj.art-48277725a2b240b086e2f01f96c1e1dd2023-11-30T20:52:37ZengMDPI AGBiology2079-77372022-03-0111347610.3390/biology11030476Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across PopulationsElvis Twumasi Aboagye0Samuel Mawuli Adadey1Kevin Esoh2Mario Jonas3Carmen de Kock4Lucas Amenga-Etego5Gordon A. Awandare6Ambroise Wonkam7West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, GhanaDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, GhanaDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaGap 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.https://www.mdpi.com/2079-7737/11/3/476connexin 26 (Cx26)non-syndromic hearing impairment<i>GJB2</i>-p.Arg143Trp (c.427C > T) founder variantvariant originGhana |
| spellingShingle | Elvis Twumasi Aboagye Samuel Mawuli Adadey Kevin Esoh Mario Jonas Carmen de Kock Lucas Amenga-Etego Gordon A. Awandare Ambroise Wonkam Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations Biology connexin 26 (Cx26) non-syndromic hearing impairment <i>GJB2</i>-p.Arg143Trp (c.427C > T) founder variant variant origin Ghana |
| title | Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations |
| title_full | Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations |
| title_fullStr | Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations |
| title_full_unstemmed | Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations |
| title_short | Age Estimate of <i>GJB2</i>-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations |
| title_sort | age estimate of i gjb2 i p arg143trp founder variant in hearing impairment in ghana suggests multiple independent origins across populations |
| topic | connexin 26 (Cx26) non-syndromic hearing impairment <i>GJB2</i>-p.Arg143Trp (c.427C > T) founder variant variant origin Ghana |
| url | https://www.mdpi.com/2079-7737/11/3/476 |
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