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

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dc.contributor.authorAboagye, Elvis Twumasi
dc.contributor.authorAdadey, Samuel Mawuli
dc.contributor.authorEsoh, Kevin
dc.contributor.authorJonas, Mario
dc.contributor.authorde Kock, Carmen
dc.contributor.authorAmenga-Etego, Lucas
dc.contributor.authorAwandare, Gordon A
dc.contributor.authorWonkam, Ambroise
dc.date.accessioned2022-04-13T08:14:59Z
dc.date.available2022-04-13T08:14:59Z
dc.date.issued2022-03-21
dc.date.updated2022-03-24T14:46:56Z
dc.description.abstractGap junction protein beta 2 (GJB2) (connexin 26) variants are commonly implicated in non-syndromic hearing impairment (NSHI). In Ghana, the GJB2 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, GJB2-p.(Arg143Trp) has only been reported in Ghana. Using wholeexome 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 GJB2-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 GJB2-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 GJB2- p.(Arg143Trp) compared to the GJB2-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 GJB2-p.(Arg143Trp). The present study evaluates the age of GJB2-p.(Arg143Trp) at 9625 years and supports the multiple independent origins of this variant in the global population.en_US
dc.identifierdoi: 10.3390/biology11030476
dc.identifier.apacitationAboagye, E. T., Adadey, S. M., Esoh, K., Jonas, M., de Kock, C., Amenga-Etego, L., ... Wonkam, A. (2022). Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations. <i>Biology</i>, 11(3), 476. http://hdl.handle.net/11427/36356en_ZA
dc.identifier.chicagocitationAboagye, Elvis Twumasi, Samuel Mawuli Adadey, Kevin Esoh, Mario Jonas, Carmen de Kock, Lucas Amenga-Etego, Gordon A Awandare, and Ambroise Wonkam "Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations." <i>Biology</i> 11, 3. (2022): 476. http://hdl.handle.net/11427/36356en_ZA
dc.identifier.citationAboagye, E.T., Adadey, S.M., Esoh, K., Jonas, M., de Kock, C., Amenga-Etego, L., Awandare, G.A. & Wonkam, A. et al. 2022. Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations. <i>Biology.</i> 11(3):476. http://hdl.handle.net/11427/36356en_ZA
dc.identifier.risTY - Journal Article AU - Aboagye, Elvis Twumasi AU - Adadey, Samuel Mawuli AU - Esoh, Kevin AU - Jonas, Mario AU - de Kock, Carmen AU - Amenga-Etego, Lucas AU - Awandare, Gordon A AU - Wonkam, Ambroise AB - 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. DA - 2022-03-21 DB - OpenUCT DP - University of Cape Town IS - 3 J1 - Biology KW - connexin 26 (Cx26) LK - https://open.uct.ac.za PY - 2022 T1 - Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations TI - Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations UR - http://hdl.handle.net/11427/36356 ER -en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/36356
dc.identifier.vancouvercitationAboagye ET, Adadey SM, Esoh K, Jonas M, de Kock C, Amenga-Etego L, et al. Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations. Biology. 2022;11(3):476. http://hdl.handle.net/11427/36356.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDivision of Human Geneticsen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceBiologyen_US
dc.source.journalissue3en_US
dc.source.journalvolume11en_US
dc.source.pagination476en_US
dc.source.urihttps://www.mdpi.com/journal/biology
dc.subjectconnexin 26 (Cx26)en_US
dc.subjectnon-syndromic hearing impairment
dc.subjectGJB2-p.Arg143Trp (c.427C > T) founder variant
dc.subjectvariant origin
dc.subjectGhana
dc.titleAge Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populationsen_US
dc.typeJournal Articleen_US
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