Hearing Impairment Genetics Studies in Africa (HI-GENES Africa)

非洲听力障碍遗传学研究（HI-GENES Africa）

• 批准号: 10204072
• 负责人: AMBROISE WONKAM
• 金额: $ 26.2万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204072
• 关键词: 6 year old; Affect; Africa; African; African American; American; Asia; Auditory; Bioinformatics; Cameroon; Cochlear Implants; Copy Number Polymorphism; Country; Data; Data Analyses; Data Set; Databases; Diagnosis; Diagnostic; Dideoxy Chain Termination DNA Sequencing; East Indian; Europe; Evaluation; Family; Family history of; Family member; Functional disorder; Future; GJB2 gene; GJB6 gene; Gene Frequency; Generations; Genes; Genetic Predisposition to Disease; Genetic Screening; Genetic study; Genomics; Ghana; Hearing; Hearing Tests; Hispanic Americans; Knowledge; Mali; Maps; Massive Parallel Sequencing; Middle East; Minority Groups; Modality; Mutation; Parents; Pathogenicity; Population; Prevalence; Probability; Process; Public Health; Quality Control; Sample Size; Sampling; Siblings; South Africa; Syndrome; Testing; Therapeutic Intervention; Treatment outcome; Untranslated RNA; Variant; causal variant; early onset; early screening; exome; exome sequencing; experience; follow-up; genetic variant; genome sequencing; hearing impairment; hereditary hearing loss; improved; insight; member; mitochondrial genome; next generation sequence data; novel; ototoxicity; proband; rare variant; research clinical testing; segregation; therapeutic development; tool; whole genome

HI-GENES Africa Project Summary/Abstract Despite a large number of identified genes, only GJB2 and GJB6 have been systematically studied in sub-Saharan Africans, for which prevalence of NSHI-causal variants is close to zero and we estimate known NSHI genes only explain ~4.1% of autosomal recessive (AR) NSHI in African-Americans. In the current project called HI-GENES Africa, referring to Hearing Impairment Genetics Studies in Africa, we propose to use Whole genome sequencing (WES), to study to date, the largest sample of sub-Saharan Africans from Cameroon, Mali, Ghana, and South Africa with prelingual ARNSHI in order to identify novel NSHI genes and to better understand the genetic etiology of NSHI in African populations. Aim 1) Ascertain families and probands with early-onset NSHI from Cameroon, Mali, Ghana, and South Africa. We will ascertain 125 families that segregate early-onset (<6 years of age) ARNSHI. For each family multiple affected (at least two per family) and unaffected members will be ascertained. Additionally, 500 probands with early-onset HI (<6 years of age) with strong evidence of having ARNSHI will be ascertained. The probands and family members will be carefully evaluated by clinical and audiometric testing to rule out syndromic HI and HI due to infectious and ototoxic exposures. Aim 2) Generate next generation sequence data on hearing-impaired family members. For each family, we will exome-sequence (including the mitochondrial genome) samples, from two affected family members, and follow up variants segregating in their parents and at least one non-affected sibling and a control non- affected population. We anticipate from previous experience that for ~5% of the families (n=~8) a causal variant will not be identified using exome sequencing, due to insufficient read depth or variant is in non-coding region. These families will be followed-up by generating whole genome sequence (WGS) data that also help to identify copy number variants. Aim 3) Analyze sequence data to identify novel NSHI genes. Using Variant Mendelian Tools we will annotate the identified variants and analyze rare variants (allele frequency<0.005 according to the ExAC database and sequencing data from Cameroon, Mali, Ghana, and South Africa Controls). Bioinformatic evaluation using multiple tools will be used to predict which variants are deleterious. Segregation of rare damaging variants will be tested in families. Given the large sample size there is a very high probability of identifying a number of novel NSHI genes in multiple families. HI-GENES Africa has high public health significance in particular for minority populations, since it will improve genetic screening and in the future prediction of cochlear implant and treatment outcomes in sub-Saharan Africans, African-Americans and Hispanic-Americans of African descent.

HI-GENES非洲项目摘要/摘要

项目成果

Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali.

• DOI: 10.3389/fped.2021.726776
• 发表时间: 2021
• 期刊: Frontiers in pediatrics
• 影响因子: 2.6
• 作者: Yalcouyé A;Traoré O;Taméga A;Maïga AB;Kané F;Oluwole OG;Guinto CO;Kéita M;Timbo SK;DeKock C;Landouré G;Wonkam A
• 通讯作者: Wonkam A

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

• DOI: 10.3390/biology11030476
• 发表时间: 2022-03-21
• 期刊: Biology
• 影响因子: 4.2
• 作者: Aboagye ET;Adadey SM;Esoh K;Jonas M;de Kock C;Amenga-Etego L;Awandare GA;Wonkam A
• 通讯作者: Wonkam A

Craniofacial, dental, and molecular features of Pyle disease in a South African child.

• DOI: 10.1038/s41405-022-00120-w
• 发表时间: 2022-09-22
• 期刊: BDJ OPEN
• 影响因子: 3
• 作者: Chetty, Manogari;Roomaney, Imaan;Oosterwyk, Chandre;Manyisa, Noluthando;Bope, Christian Domilongo;Agenbag, Gloudi;Wonkam, Ambroise
• 通讯作者: Wonkam, Ambroise

Cell-based analysis of CLIC5A and SLC12A2 variants associated with hearing impairment in two African families.

• DOI: 10.3389/fgene.2022.924904
• 发表时间: 2022
• 期刊: FRONTIERS IN GENETICS
• 影响因子: 3.7
• 作者: Adadey, Samuel Mawuli;Wonkam-Tingang, Edmond;de Souza Rios, Leonardo Alves;Aboagye, Elvis Twumasi;Esoh, Kevin;Manyisa, Noluthando;De Kock, Carmen;Awandare, Gordon A.;Mowla, Shaheen;Wonkam, Ambroise
• 通讯作者: Wonkam, Ambroise

Childhood Hearing Impairment in Senegal.

• DOI: 10.3390/genes14030562
• 发表时间: 2023-02-23
• 期刊: Genes
• 影响因子: 3.5