Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

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dc.contributor.authorOluwole, Oluwafemi G.en_ZA
dc.contributor.authorKuivaniemi, Helenaen_ZA
dc.contributor.authorAbrahams, Shameemahen_ZA
dc.contributor.authorHaylett, William L.en_ZA
dc.contributor.authorVorster, Alvera A.en_ZA
dc.contributor.authorVan Heerden, Carel J.en_ZA
dc.contributor.authorKenyon, Colin P.en_ZA
dc.contributor.authorTabb, David L.en_ZA
dc.contributor.authorFawale, Michael B.en_ZA
dc.contributor.authorSunmonu, Taofiki A.en_ZA
dc.contributor.authorAjose, Abiodunen_ZA
dc.contributor.authorOlaogun, Matthew O.en_ZA
dc.contributor.authorRossouw, Anastasia C.en_ZA
dc.contributor.authorVan Hillegondsberg, Ludo S.en_ZA
dc.contributor.authorCarr, Jonathanen_ZA
dc.contributor.authorRoss, Owen A.en_ZA
dc.contributor.authorKomolafe, Morenikeji A.en_ZA
dc.contributor.authorTromp, Gerarden_ZA
dc.contributor.authorBardien, Sorayaen_ZA
dc.date.accessioned2020-02-10T06:31:02Z
dc.date.available2020-02-10T06:31:02Z
dc.date.issued2020-02-04
dc.date.updated2020-02-09T04:57:36Z
dc.descriptionCITATION: Oluwole, O. G., et al. 2020. Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients. BMC Medical Genetics, 21:23, doi:10.1186/s12881-020-0953-1.
dc.descriptionThe original publication is available at https://bmcmedgenet.biomedcentral.com
dc.description.abstractBackground: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.en_ZA
dc.description.urihttps://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-020-0953-1
dc.description.versionPublisher's version
dc.format.extent11 pages
dc.identifier.citationOluwole, O. G., et al. 2020. Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients. BMC Medical Genetics, 21:23, doi:10.1186/s12881-020-0953-1
dc.identifier.issn1471-2350 (online)
dc.identifier.otherdoi:10.1186/s12881-020-0953-1
dc.identifier.urihttp://hdl.handle.net/10019.1/107454
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Central
dc.rights.holderAuthors retain copyright
dc.subjectParkinson’s disease -- Africa, Sub-Saharanen_ZA
dc.subjectParkinson’s disease -- Genetic aspectsen_ZA
dc.subjectGene targetingen_ZA
dc.titleTargeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patientsen_ZA
dc.typeArticle
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