Browsing by Author "Abrahams, Shameemah"

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    Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients
    (BioMed Central, 2020-02-04) Oluwole, Oluwafemi G.; Kuivaniemi, Helena; Abrahams, Shameemah; Haylett, William L.; Vorster, Alvera A.; Van Heerden, Carel J.; Kenyon, Colin P.; Tabb, David L.; Fawale, Michael B.; Sunmonu, Taofiki A.; Ajose, Abiodun; Olaogun, Matthew O.; Rossouw, Anastasia C.; Van Hillegondsberg, Ludo S.; Carr, Jonathan; Ross, Owen A.; Komolafe, Morenikeji A.; Tromp, Gerard; Bardien, Soraya
    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.
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    Unravelling the interaction between the DRD2 and DRD4 genes, personality traits and concussion risk
    (BMJ Publishing Group, 2019) Abrahams, Shameemah; McFie, Sarah; Lacerda, Miguel; Patricios, Jon; Suter, Jason; September, Alison V.; Posthumus, Michael
    Background: Concussion occurs when biomechanical forces transmitted to the head result in neurological deficits. Personality may affect the balance between safe and dangerous play potentially influencing concussion risk. Dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) genetic polymorphisms were previously associated with personality traits. Objectives: This case–control genetic association study investigated the associations of (1) DRD2 and DRD4 genotypes with concussion susceptibility and personality, (2) personality with concussion susceptibility and (3) the statistical model of genotype, personality and concussion susceptibility. Methods: In total, 138 non-concussed controls and 163 previously concussed cases were recruited from high school (n=135, junior), club and professional rugby teams (n=166, senior). Participants were genotyped for DRD2 rs12364283 (A>G), DRD2 rs1076560 (C>A) and DRD4 rs1800955 (T>C) genetic variants. Statistical analyses including structural equation modelling were performed using the R environment and STATA. Results: The rs1800955 CC genotype (p=0.014) and inferred DRD2 (rs12364283–rs1076560)–DRD4 (rs1800955) A–C–C allele combination (p=0.019) were associated with decreased concussion susceptibility in juniors. The rs1800955 TT and CT genotypes were associated with low reward dependence in juniors (p<0.001) and seniors (p=0.010), respectively. High harm avoidance was associated with decreased concussion susceptibility in juniors (p=0.009) and increased susceptibility in seniors (p=0.001). The model showed that a genetic variant was associated with personality while personality was associated with concussion susceptibility. Conclusion: These findings highlight the linear relationship between genetics, personality and concussion susceptibility. Identifying a genetic profile of ‘high risk’ behaviour, together with the development of personalised behavioural training, can potentially reduce concussion risk.