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

Autor: Oluwole OG; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa., Kuivaniemi H; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa., Abrahams S; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa., Haylett WL; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.; Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Vorster AA; DNA Sequencing Unit, Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa., van Heerden CJ; DNA Sequencing Unit, Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa., Kenyon CP; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.; Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa.; DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa., Tabb DL; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.; Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa.; DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.; Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa., Fawale MB; Neurology Unit, Department of Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Sunmonu TA; Neurology Unit, Department of Medicine, Federal Medical Centre, Owo, Nigeria., Ajose A; Department of Chemical Pathology, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Olaogun MO; Department of Medical Rehabilitation, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Rossouw AC; Division of Neurology, Department of Medicine, Faculty of Health Sciences, Walter Sisulu University, East London, South Africa., van Hillegondsberg LS; Division of Neurology, Department of Medicine, Faculty of Health Sciences, Walter Sisulu University, East London, South Africa.; Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Carr J; Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Ross OA; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.; Department of Clinical Genomics, Mayo Clinic College of Medicine, Jacksonville, Florida, USA., Komolafe MA; Neurology Unit, Department of Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Tromp G; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa. gctromp@sun.ac.za., Bardien S; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa. sbardien@sun.ac.za.
Jazyk: angličtina
Zdroj: BMC medical genetics [BMC Med Genet] 2020 Feb 04; Vol. 21 (1), pp. 23. Date of Electronic Publication: 2020 Feb 04.
DOI: 10.1186/s12881-020-0953-1
Abstrakt: Background: 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.
Databáze: MEDLINE
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