Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa.

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dc.contributor.authorEkure, E.N.
dc.contributor.authorAdeyemo, A.
dc.contributor.authorLiu, H.
dc.contributor.authorSokunbi, O.
dc.contributor.authorKalu, N.
dc.contributor.authorMartinez, A.F.
dc.contributor.authorOwosela, B.
dc.contributor.authorTekendo-Ngongang, C.
dc.contributor.authorAddissie, Y.A.
dc.contributor.authorOlusegun-Joseph, A.
dc.contributor.authorIkebudu, D.
dc.contributor.authorBerger, S.I.
dc.contributor.authorMuenke, M.
dc.contributor.authorHan, Z.
dc.contributor.authorKruszka, P.
dc.date.accessioned2021-02-22T08:20:52Z
dc.date.available2021-02-22T08:20:52Z
dc.date.issued2021-01-15
dc.descriptionScholarly articlesen_US
dc.description.abstractBackground: Congenital heart disease (CHD) is the most common birth defect and affects roughly 1% of the global population. There have been many large CHD sequencing projects in developing countries but none in sub-Saharan Africa. In this exome sequencing study, we recruited families from Lagos, Nigeria, affected by structural heart disease. Methods: Ninety-eight participants with CHD and an average age of 3.6 years were recruited from Lagos, Nigeria. Exome sequencing was performed on probands and parents when available. For genes of high interest, we conducted functional studies in Drosophila using a cardiac-specific RNA interference-based gene silencing system. Results: The 3 most common CHDs were tetralogy of Fallot (20%), isolated ventricular septal defect (14%), and transposition of the great arteries (8%). Ten percent of the cohort had pathogenic or likely pathogenic variants in genes known to cause CHD. In 64 complete trios, we found 34 de novo variants that were not present in the African population in the Genome Aggregation Database (v3). Nineteen loss of function variants were identified using the genome-wide distribution of selection effects for heterozygous protein-truncating variants (shet). Nine genes caused a significant mortality when silenced in the Drosophila heart, including 4 novel disease genes not previously associated with CHD (UBB, EIF4G3, SREBF1, and METTL23). Conclusions: This study identifies novel candidate genes and variants for CHD and facilitates comparisons with previous CHD sequencing studies in predominantly European cohorts. The study represents an important first step in genomic studies of CHD in understudied populations. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01952171.en_US
dc.description.sponsorshipGrants from the NIH to Z.H. (R01-HL134940) and National Human Genome Research Institute Intramural Research Program.en_US
dc.identifier.citationEkure EN, Adeyemo A, Liu H, Sokunbi O, Kalu N, Martinez AF, Owosela B, Tekendo-Ngongang C, Addissie YA, Olusegun-Joseph A, Ikebudu D, Berger SI, Muenke M, Han Z, Kruszka P. Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa. Circ Genom Precis Med. 2021 Feb;14(1):e003108. doi: 10.1161/CIRCGEN.120.003108. Epub 2021 Jan 15. PMID: 33448881; PMCID: PMC7887052.en_US
dc.identifier.otherURL: https://www.ahajournals.org/eprint/YBPMEXBDZQ9VUX65YHZ6/full?redirectUri=%2Fdoi%2F10.1161%2FCIRCGEN.120.003108
dc.identifier.urihttps://ir.unilag.edu.ng/handle/123456789/9179
dc.language.isoenen_US
dc.publisherLippincott Williams and Wilkins Ltden_US
dc.subjectDrosophilaen_US
dc.subjectNigeriaen_US
dc.subjectTetralogy of Falloten_US
dc.subjectExomeen_US
dc.subjectHeart diseaseen_US
dc.subjectResearch Subject Categories::MEDICINEen_US
dc.titleExome Sequencing and Congenital Heart Disease in Sub-Saharan Africa.en_US
dc.typeArticleen_US
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