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.

中文翻译：

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靶向下一代测序鉴定了南非黑人和尼日利亚患者帕金森病候选基因的新变异。


背景技术帕金森病（PD）在撒哈拉以南非洲地区的患病率正在增加，但人们对这些人群中帕金森病的遗传学知之甚少。由于其独特的血统和多样性，撒哈拉以南非洲人群有可能揭示帕金森病病理学的新见解。在这项研究中，我们的目的是描述一组南非和尼日利亚黑人患者中已知和新的 PD 基因的遗传变异。方法 我们招募了 33 名南非黑人和 14 名尼日利亚 PD 患者，并使用 Ion AmpliSeq™ 神经学研究小组对他们进行了 751 个基因的序列变异筛查。我们使用 bcftools 来过滤变体并使用 annovar 软件进行注释。使用 MetaLR 和 MetaSVM 预测分数对罕见变异进行优先排序。通过分子建模研究了变体对 ATP13A2 蛋白质结构的影响。结果 我们鉴定了 14,655 个次要等位基因频率≤ 0.01 的罕见变异，其中包括 2448 个错义变异。值得注意的是，在这些患者中没有发现常见的致病突变。此外，没有发现任何已知的帕金森病相关突变，这凸显了在非洲人群中进行更多研究的必要性。总共，42 个基因中的 54 个罕见变异被认为是有害的，并根据 MetaLR 和 MetaSVM 评分优先进行后续研究。蛋白质模型显示 ATP13A2 中的 S1004R 变体可能会改变蛋白质的构象。结论 我们发现了几种预计对撒哈拉以南非洲帕金森病患者有害的罕见变异。然而，还需要进一步的研究来确定这些变异的生物学效应及其在帕金森病中可能的作用。 诸如此类的研究对于阐明非洲血统患者这种疾病的遗传病因学非常重要。