Browsing by Author "Gamieldien, Junaid"

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    Open Access
    The development of computational biology in South Africa: successes achieved and lessons learnt
    (Public Library of Science, 2016) Mulder, Nicola J; Christoffels, Alan; De Oliveira, Tulio; Gamieldien, Junaid; Hazelhurst, Scott; Joubert, Fourie; Kumuthini, Judit; Pillay, Ché S; Snoep, Jacky L; Bishop, Özlem Tastan; Tiffin, Nicki
    Bioinformatics is now a critical skill in many research and commercial environments as biological data are increasing in both size and complexity. South African researchers recognized this need in the mid-1990s and responded by working with the government as well as international bodies to develop initiatives to build bioinformatics capacity in the country. Significant injections of support from these bodies provided a springboard for the establishment of computational biology units at multiple universities throughout the country, which took on teaching, basic research and support roles. Several challenges were encountered, for example with unreliability of funding, lack of skills, and lack of infrastructure. However, the bioinformatics community worked together to overcome these, and South Africa is now arguably the leading country in bioinformatics on the African continent. Here we discuss how the discipline developed in the country, highlighting the challenges, successes, and lessons learnt.
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    Open Access
    Exome sequencing identifies novel dysferlin mutation in a family with pauci-symptomatic heterozygous carriers
    (BioMed Central, 2018-06-07) Jalali-Sefid-Dashti, Mahjoubeh; Nel, Melissa; Heckmann, Jeannine M; Gamieldien, Junaid
    Background We investigated a South African family of admixed ancestry in which the first generation (G1) developed insidious progressive distal to proximal weakness in their twenties, while their offspring (G2) experienced severe unexpected symptoms of myalgia and cramps since adolescence. Our aim was to identify deleterious mutations that segregate with the affected individuals in this family. Methods Exome sequencing was performed on five cases, which included three affected G1 siblings and two pauci-symptomatic G2 offspring. As controls we included an unaffected G1 sibling and a spouse of one of the G1 affected individuals. Homozygous or potentially compound heterozygous variants that were predicted to be functional and segregated with the affected G1 siblings, were further evaluated. Additionally, we considered variants in all genes segregating exclusively with the affected (G1) and pauci-symptomatic (G2) individuals to address the possibility of a pseudo-autosomal dominant inheritance pattern in this family. Results All affected G1 individuals were homozygous for a novel truncating p.Tyr1433Ter DYSF (dysferlin) mutation, with their asymptomatic sibling and both pauci-symptomatic G2 offspring carrying only a single mutant allele. Sanger sequencing confirmed segregation of the variant. No additional potentially contributing variant was found in the DYSF or any other relevant gene in the pauci-symptomatic carriers. Conclusion Our finding of a truncating dysferlin mutation confirmed dysferlinopathy in this family and we propose that the single mutant allele is the primary contributor to the neuromuscular symptoms seen in the second-generation pauci-symptomatic carriers.
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    Population-specific common SNPs reflect demographic histories and highlight regions of genomic plasticity with functional relevance
    (2014-06-06) Choudhury, Ananyo; Hazelhurst, Scott; Meintjes, Ayton; Achinike-Oduaran, Ovokeraye; Aron, Shaun; Gamieldien, Junaid; Jalali Sefid Dashti, Mahjoubeh; Mulder, Nicola; Tiffin, Nicki; Ramsay, Michèle
    Abstract Background Population differentiation is the result of demographic and evolutionary forces. Whole genome datasets from the 1000 Genomes Project (October 2012) provide an unbiased view of genetic variation across populations from Europe, Asia, Africa and the Americas. Common population-specific SNPs (MAF > 0.05) reflect a deep history and may have important consequences for health and wellbeing. Their interpretation is contextualised by currently available genome data. Results The identification of common population-specific (CPS) variants (SNPs and SSV) is influenced by admixture and the sample size under investigation. Nine of the populations in the 1000 Genomes Project (2 African, 2 Asian (including a merged Chinese group) and 5 European) revealed that the African populations (LWK and YRI), followed by the Japanese (JPT) have the highest number of CPS SNPs, in concordance with their histories and given the populations studied. Using two methods, sliding 50-SNP and 5-kb windows, the CPS SNPs showed distinct clustering across large genome segments and little overlap of clusters between populations. iHS enrichment score and the population branch statistic (PBS) analyses suggest that selective sweeps are unlikely to account for the clustering and population specificity. Of interest is the association of clusters close to recombination hotspots. Functional analysis of genes associated with the CPS SNPs revealed over-representation of genes in pathways associated with neuronal development, including axonal guidance signalling and CREB signalling in neurones. Conclusions Common population-specific SNPs are non-randomly distributed throughout the genome and are significantly associated with recombination hotspots. Since the variant alleles of most CPS SNPs are the derived allele, they likely arose in the specific population after a split from a common ancestor. Their proximity to genes involved in specific pathways, including neuronal development, suggests evolutionary plasticity of selected genomic regions. Contrary to expectation, selective sweeps did not play a large role in the persistence of population-specific variation. This suggests a stochastic process towards population-specific variation which reflects demographic histories and may have some interesting implications for health and susceptibility to disease.