Targeted ultra-deep sequencing of a South African Bantu-speaking cohort to comprehensively map and characterize common and novel variants in 65 pharmacologically-related genes

Tshabalala, Sibongile; Choudhury, Ananyo; Beeton-Kempen, Natasha; Martinson, Neil; Ramsay, Michèle; Mancama, D

doi:10.1097/fpc.0000000000000380

Cited by 5 publications

(5 citation statements)

References 83 publications

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“…South Africa in particular has a unique and complex genetic population, resulting from admixture between the native Khoisan with Bantu and European populations [ 20 ]. Recently, deep NGS of the pharmacogenes of a Bantu-speaking cohort in South Africa revealed rare novel variants with predicted functional effects that have not been recorded in other African populations [ 69 ]. This includes the identification of novel deleterious variants in the flavin-containing monooxygenase 2 gene, which is involved in the oxygenation of sulphur-containing drugs in humans [ 69 ].…”

Section: Challenges In Genotyping Pharmacogene Variantsmentioning

confidence: 99%

“…Recently, deep NGS of the pharmacogenes of a Bantu-speaking cohort in South Africa revealed rare novel variants with predicted functional effects that have not been recorded in other African populations [ 69 ]. This includes the identification of novel deleterious variants in the flavin-containing monooxygenase 2 gene, which is involved in the oxygenation of sulphur-containing drugs in humans [ 69 ]. Distinct and highly diverse alleles of the Cytochrome P450 family have been recorded in African populations relative to other populations, highlighting the need for further dedicated PGx and functional studies on these unique variants [ 21 ].…”

Section: Challenges In Genotyping Pharmacogene Variantsmentioning

confidence: 99%

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Barriers to Implementing Clinical Pharmacogenetics Testing in Sub-Saharan Africa. A Critical Review

Tata

Ambele

2020

Pharmaceutics

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Clinical research in high-income countries is increasingly demonstrating the cost- effectiveness of clinical pharmacogenetic (PGx) testing in reducing the incidence of adverse drug reactions and improving overall patient care. Medications are prescribed based on an individual’s genotype (pharmacogenes), which underlies a specific phenotypic drug response. The advent of cost-effective high-throughput genotyping techniques coupled with the existence of Clinical Pharmacogenetics Implementation Consortium (CPIC) dosing guidelines for pharmacogenetic “actionable variants” have increased the clinical applicability of PGx testing. The implementation of clinical PGx testing in sub-Saharan African (SSA) countries can significantly improve health care delivery, considering the high incidence of communicable diseases, the increasing incidence of non-communicable diseases, and the high degree of genetic diversity in these populations. However, the implementation of PGx testing has been sluggish in SSA, prompting this review, the aim of which is to document the existing barriers. These include under-resourced clinical care logistics, a paucity of pharmacogenetics clinical trials, scientific and technical barriers to genotyping pharmacogene variants, and socio-cultural as well as ethical issues regarding health-care stakeholders, among other barriers. Investing in large-scale SSA PGx research and governance, establishing biobanks/bio-databases coupled with clinical electronic health systems, and encouraging the uptake of PGx knowledge by health-care stakeholders, will ensure the successful implementation of pharmacogenetically guided treatment in SSA.

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Section: Challenges In Genotyping Pharmacogene Variantsmentioning

confidence: 99%

Section: Challenges In Genotyping Pharmacogene Variantsmentioning

confidence: 99%

Barriers to Implementing Clinical Pharmacogenetics Testing in Sub-Saharan Africa. A Critical Review

Tata

Ambele

2020

Pharmaceutics

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“…There have been recent studies on variants in ADME (absorption, distribution, metabolism and excretion) genes in different healthy populations which are helping to identify variants and their frequencies that may be relevant in pharmacogenetics. In a study of sequence data from 40 South Africans of Bantu ancestry, 1662 variants were identified in 65 ADME genes, some of which were novel and a few were potential loss-of-function variants [ 127 ]. The novel variants may be important for moderating treatment outcome, but their effect still needs to be determined.…”

Section: Discussion and Future Perspectivementioning

confidence: 99%

A Review of Clinical Pharmacogenetics Studies in African Populations

et al. 2020

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Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.

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“…Tshabalala et al ( 63) analyzed 65 ADME genes using sequence data from 40 South Africans of Bantu ancestry, from which they identified 1,662 variants. Some of these were novel and included variants predicted to be loss of function, highlighting the importance of generating more data to identify new variants and to understand population-specific differences that may have an impact on treatment (63). Additionally, da Rocha et al (62) expanded the analysis to 299 ADME genes, using high-coverage whole-genome data from 458 individuals representative of all the regions of sub-Saharan Africa.…”

Section: Pharmacogenomics Datamentioning

confidence: 99%

African Global Representation in Biomedical Sciences

Mulder

Zass

Hamdi

et al. 2021

Annu. Rev. Biomed. Data Sci.

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African populations are diverse in their ethnicity, language, culture, and genetics. Although plagued by high disease burdens, until recently the continent has largely been excluded from biomedical studies. Along with limitations in research and clinical infrastructure, human capacity, and funding, this omission has resulted in an underrepresentation of African data and disadvantaged African scientists. This review interrogates the relative abundance of biomedical data from Africa, primarily in genomics and other omics. The visibility of African science through publications is also discussed. A challenge encountered in this review is the relative lack of annotation of data on their geographical or population origin, with African countries represented as a single group. In addition to the abovementioned limitations,the global representation of African data may also be attributed to the hesitation to deposit data in public repositories. Whatever the reason, the disparity should be addressed, as African data have enormous value for scientists in Africa and globally.

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Targeted ultra-deep sequencing of a South African Bantu-speaking cohort to comprehensively map and characterize common and novel variants in 65 pharmacologically-related genes

Abstract: Supplemental Digital Content is available in the text.

Cited by 5 publications

References 83 publications

Barriers to Implementing Clinical Pharmacogenetics Testing in Sub-Saharan Africa. A Critical Review

Barriers to Implementing Clinical Pharmacogenetics Testing in Sub-Saharan Africa. A Critical Review

A Review of Clinical Pharmacogenetics Studies in African Populations

African Global Representation in Biomedical Sciences

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