title: Sequencing of GJB2 in Cameroonians and Black South Africans and comparison to 1000 Genomes Project Data Support Need to Revise Strategy for Discovery of Nonsyndromic Deafness Genes in Africans.
abstract: Mutations in the GJB2 gene, encoding connexin 26, could account for 50% of congenital, nonsyndromic, recessive deafness cases in some Caucasian/Asian populations. There is a scarcity of published data in sub-Saharan Africans. We Sanger sequenced the coding region of the GJB2 gene in 205 Cameroonian and Xhosa South Africans with congenital, nonsyndromic deafness; and performed bioinformatic analysis of variations in the GJB2 gene, incorporating data from the 1000 Genomes Project. Amongst Cameroonian patients, 26.1% were familial. The majority of patients (70%) suffered from sensorineural hearing loss. Ten GJB2 genetic variants were detected by sequencing. A previously reported pathogenic mutation, g.3741_3743delTTC (p.F142del), and a putative pathogenic mutation, g.3816G>A (p.V167M), were identified in single heterozygous samples. Amongst eight the remaining variants, two novel variants, g.3318-41G>A and g.3332G>A, were reported. There were no statistically significant differences in allele frequencies between cases and controls. Principal Components Analyses differentiated between Africans, Asians, and Europeans, but only explained 40% of the variation. The present study is the first to compare African GJB2 sequences with the data from the 1000 Genomes Project and have revealed the low variation between population groups. This finding has emphasized the hypothesis that the prevalence of mutations in GJB2 in nonsyndromic deafness amongst European and Asian populations is due to founder effects arising after these individuals migrated out of Africa, and not to a putative "protective" variant in the genomic structure of GJB2 in Africans. Our results confirm that mutations in GJB2 are not associated with nonsyndromic deafness in Africans.
authors.affiliation: 1 Division of Human Genetics, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Jason
authors.initials: J
authors.lastname: Bosch
authors.forename: Jean Jacques N
authors.initials: JJ
authors.lastname: Noubiap
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.forename: Nomlindo
authors.initials: N
authors.lastname: Makubalo
authors.forename: Galen
authors.initials: G
authors.lastname: Wright
authors.forename: Jean-Baka Domelevo
authors.initials: JB
authors.lastname: Entfellner
authors.forename: Nicki
authors.initials: N
authors.lastname: Tiffin
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D002163:Cameroon; D019295:Computational Biology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000151:congenital / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010802:Phylogeny; D013019:South Africa
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26