Browsing by Author "Pepper, Michael S."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    ASSAf consensus study on the ethical, legal and social implications of genetics and genomics in South Africa
    (Academy of Science of South Africa, 2018) Pepper, Michael S.; Dandara, Collet; De Vries, Jantina; Dhai, Amaboo; Labuschaigne, Melodie; Mnyongani, Freddy; Moodley, Keymanthri; Olckers, Antonel; Pope, Anne; Ramesar, Raj; Ramsay, Michele; Soodyall, Himla; Towers, Wayne
    No abstract available.
  • Thumbnail Image
    Item
    Introduction of the AmpliChip CYP450 Test to a South African cohort : a platform comparative prospective cohort study
    (BioMed Central, 2013-01) Dodgen, Tyren M.; Hochfeld, Warren E.; Fickl, Heidi; Asfaha, Sahle M.; Durandt, Chrisna; Rheeder, Paul; Drogemoller, Britt I.; Wright, Galen E. B.; Warnich, Louise; Labuschagne, Christiaan D. J.; Van Schalkwyk, Antoinette; Gaedigk, Andrea; Pepper, Michael S.
    Abstract Background Adverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 Test® (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population. Methods AmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles. Results Even though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. The CYP2D6 XL-PCR + Sequencing platform detected CYP2D6*5 more reliably and could correctly distinguish between CYP2D6*2 and *41 in the Black African individuals. Alleles not covered by the AmpliChip were identified and four novel CYP2D6 alleles were also detected. CYP2C19 PCR-RFLP identified CYP2C19*9,*15, *17 and *27 in the Black African individuals, with *2, *17 and *27 being relatively frequent in the cohort. Eliminating mismatches and identifying additional alleles will contribute to improving phenotype prediction for both enzymes. Phenotype prediction differed between platforms for both genes. Conclusion Comprehensive genotyping of CYP2D6 and CYP2C19 with the platforms used in this study, would be more appropriate than AmpliChip for phenotypic prediction in the South African population. Pharmacogenetically important novel alleles may remain undiscovered when using assays that are designed according to Caucasian specific variation, unless alternate strategies are utilised.
  • Thumbnail Image
    Item
    Pharmacogenomic research in South Africa : lessons learned and future opportunities in the rainbow nation
    (Bentham Science, 2011-09) Warnich, Louise; Drogemoller, Britt I.; Pepper, Michael S.; Dandara, Collet; Wright, Galen E.B.
    ENGLISH ABSTRACT: South Africa, like many other developing countries, stands to benefit from novel diagnostics and drugs developed by pharmacogenomics guidance due to high prevalence of disease burden in the region. This includes both communicable (e.g., HIV/AIDS and tuberculosis) and non-communicable (e.g., diabetes and cardiovascular) diseases. For example, although only 0.7% of the world’s population lives in South Africa, the country carries 17% of the global HIV/AIDS burden and 5% of the global tuberculosis burden. Nobel Peace Prize Laureate Archbishop Emeritus Desmond Tutu has coined the term Rainbow Nation, referring to a land of wealth in its many diverse peoples and cultures. It is now timely and necessary to reflect on how best to approach new genomics biotechnologies in a manner that carefully considers the public health needs and extant disease burden in the region. The aim of this paper is to document and review the advances in pharmacogenomics in South Africa and importantly, to evaluate the direction that future research should take. Previous research has shown that the populations in South Africa exhibit unique allele frequencies and novel genetic variation in pharmacogenetically relevant genes, often differing from other African and global populations. The high level of genetic diversity, low linkage disequilibrium and the presence of rare variants in these populations question the feasibility of the use of current commercially available genotyping platforms, and may partially account for genotypephenotype discordance observed in past studies. However, the employment of high throughput technologies for genomic research, within the context of large clinical trials, combined with interdisciplinary studies and appropriate regulatory guidelines, should aid in acceleration of pharmacogenomic discoveries in high priority therapeutic areas in South Africa. Finally, we suggest that projects such as the H3Africa Initiative, the SAHGP and PGENI should play an integral role in the coordination of genomic research in South Africa, but also other African countries, by providing infrastructure and capital to local researchers, as well as providing aid in addressing the computational and statistical bottlenecks encountered at present.
  • Thumbnail Image
    Item
    Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans
    (Nature Research (part of Springer Nature), 2017) Choudhury, Ananyo; Ramsay, Michele; Hazelhurst, Scott; Aron, Shaun; Bardien, Soraya; Botha, Gerrit; Chimusa, Emile R.; Christoffels, Alan; Gamieldien, Junaid; Sefid-Dashti, Mahjoubeh J.; Joubert, Fourie; Meintjes, Ayton; Mulder, Nicola; Ramesar, Raj; Rees, Jasper; Scholtz, Kathrine; Sengupta, Dhriti; Soodyall, Himla; Venter, Philip; Warnich, Louise; Pepper, Michael S.
    ENGLISH ABSTRACT: The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.