60 research outputs found
Pharmacogenetics of African populations : variation in major drug metabolising enzyme genes and potential impact on personalised medicine.
No full textIncludes bibliographical references (leaves 167-200
Challenges and Considerations for Delivering Bioinformatics Training in LMICs: Perspectives From Pan-African and Latin American Bioinformatics Networks
No full text© 2021 Ras, Carvajal-López, Gopalasingam, Matimba, Chauke, Mulder, Guerfali, Del Angel, Reyes, Oliveira, De Las Rivas and Cristancho.In general, institutions and research groups based in Low to Middle Income Countries (LMICs) battle a number of challenges ranging from a shortage of infrastructure, lack of training facilities, and poor internet, to a lack of local expertise (Karikari et al., 2015; Tastan Bishop et al., 2015; Shaffer et al., 2019). A shortage of local experts, particularly within more specialised topics, still remains a key obstacle in developing bioinformatics research capacity within LMICs (Tastan Bishop et al., 2015; Mulder et al., 2018).The authors who contributed to this manuscript are funded in whole, or in part, by the Wellcome Trust (WT108749/Z/15/Z), (WT108749/Z/15/A), H3ABioNet NIH grant U24HG006941, H3ABioNet NIH grant U24HG006942,
CABANA—Capacity building for bioinformatics in Latin America’ (CABANA), funded by UKRI-BBSRC on behalf of the Global Challenges Research Fund (BB/P027849/1), CSIC/ USAL and EMBL-EBI
H3Africa: current perspectives
No full textNicola Mulder,1 Alash’le Abimiku,2 Sally N Adebamowo,3 Jantina de Vries,4 Alice Matimba,5 Paul Olowoyo,6 Michele Ramsay,7 Michelle Skelton,1 Dan J Stein8,9 On behalf of the members of the H3Africa Consortium 1Computational Biology Division, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; 2International Research Center of Excellence, Institute of Human Virology, Abuja, Nigeria; 3Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA; 4Department of Medicine, University of Cape Town, Cape Town, South Africa; 5Advanced Courses and Scientific Conferences, Wellcome Genome Campus, Hinxton, UK; 6Federal Teaching Hospital, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria; 7Sydney Brenner Institute for Molecular Bioscience, Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 8Department of Psychiatry and Mental Health, University of Cape Town, 9MRC Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa Abstract: Precision medicine is being enabled in high-income countries by the growing availability of health data, increasing knowledge of the genetic determinants of disease and variation in response to treatment (pharmacogenomics), and the decreasing costs of data generation, which promote routine application of genomic technologies in the health sector. However, there is uncertainty about the feasibility of applying precision medicine approaches in low- and middle-income countries, due to the lack of population-specific knowledge, skills, and resources. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive new research into the genetic and environmental basis for human diseases of relevance to Africans as well as to build capacity for genomic research on the continent. Precision medicine requires this capacity, in addition to reference data on local populations, and skills to analyze and interpret genomic data from the bedside. The H3Africa consortium is collectively processing samples and data for over 70,000 participants across the continent, accompanied in most cases by rich clinical information on a variety of non-communicable and infectious diseases. These projects are increasingly providing novel insights into the genetic basis of diseases in indigenous populations, insights that have the potential to drive the development of new diagnostics and treatments. The consortium has also invested significant resources into establishing high-quality biorepositories in Africa, a bioinformatic network, and a strong training program that has developed skills in genomic data analysis and interpretation among bioinformaticians, wet-lab researchers, and health-care professionals. Here, we describe the current perspectives of the H3Africa consortium and how it can contribute to making precision medicine in Africa a reality. Keywords: H3Africa, genomic medicine, precision medicine, training, population genetics, diseas
Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects
No full textPharmacogenetics enables personalised therapy based on genetic profiling and is increasingly applied in drug discovery. Medicines are developed and used together with pharmacodiagnostic tools to achieve desired drug efficacy and safety margins. Genetic polymorphism of drug-metabolising enzymes such as cytochrome P450s (CYPs) and N-acetyltransferases (NATs) has been widely studied in Caucasian and Asian populations, yet studies on African variants have been less extensive. The aim of the present study was to search for novel variants of CYP2C9, CYP2C19, CYP2D6 and NAT2 genes in Africans, with a particular focus on their prevalence in different populations, their relevance to enzyme functionality and their potential for personalised therapy. Blood samples from various ethnic groups were obtained from the AiBST Biobank of African Populations. The nine exons and exon-intron junctions of the CYP genes and exon 2 of NAT2 were analysed by direct DNA sequencing. Computational tools were used for the identification, haplotype analysis and prediction of functional effects of novel single nucleotide polymorphisms (SNPs). Novel SNPs were discovered in all four genes, grouped to existing haplotypes or assigned new allele names, if possible. The functional effects of non-synonymous SNPs were predicted and known African-specific variants were confirmed, but no significant differences were found in the frequencies of SNPs between African ethnicities. The low prevalence of our novel variants and most known functional alleles is consistent with the generally high level of diversity in gene loci of African populations. This indicates that profiles of rare variants reflecting interindividual variability might become the most relevant pharmacodiagnostic tools explaining Africans' diversity in drug response
Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects
No full textAbstract Pharmacogenetics enables personalised therapy based on genetic profiling and is increasingly applied in drug discovery. Medicines are developed and used together with pharmacodiagnostic tools to achieve desired drug efficacy and safety margins. Genetic polymorphism of drug-metabolising enzymes such as cytochrome P450s (CYPs) and N-acetyltransferases (NATs) has been widely studied in Caucasian and Asian populations, yet studies on African variants have been less extensive. The aim of the present study was to search for novel variants of CYP2C9, CYP2C19, CYP2D6 and NAT2 genes in Africans, with a particular focus on their prevalence in different populations, their relevance to enzyme functionality and their potential for personalised therapy. Blood samples from various ethnic groups were obtained from the AiBST Biobank of African Populations. The nine exons and exon-intron junctions of the CYP genes and exon 2 of NAT2 were analysed by direct DNA sequencing. Computational tools were used for the identification, haplotype analysis and prediction of functional effects of novel single nucleotide polymorphisms (SNPs). Novel SNPs were discovered in all four genes, grouped to existing haplotypes or assigned new allele names, if possible. The functional effects of non-synonymous SNPs were predicted and known African-specific variants were confirmed, but no significant differences were found in the frequencies of SNPs between African ethnicities. The low prevalence of our novel variants and most known functional alleles is consistent with the generally high level of diversity in gene loci of African populations. This indicates that profiles of rare variants reflecting interindividual variability might become the most relevant pharmacodiagnostic tools explaining Africans' diversity in drug response.</p
Patient-centric research in the time of COVID-19: conducting ethical COVID-19 research in Africa
No full textResearch practices should be ethical and transparent, prioritising patient benefits and provision of health carehealthcare, and respecting participant autonomy.Priority should be given to research studies with the potential for immediate translated patient benefits based on realistic interventions appropriate to an African context. Institutional Ethics Review Boards should be supported to ensure high-quality, rapid review of research proposals. Informed consent models should reflect research risk level and the heightened vulnerability of the study population during a health crisis. Consideration should be made for patients who are too ill to give consent, and inclusion of data from deceased patients. Participant information must be accessible and relevant to participants, in local languages, and include clear, realistic descriptions of potential benefits and risks. Community engagement using appropriate media channels can be effective in providing information and counter dissemination of false information. Funders and journal editors can provide additional checks and balances to ensure funded and published research from Africa is ethical, patient-centric, relevant and transparent
Knowledge, Attitude, and Perceptions of Pharmacists and Pharmacy Students towards Pharmacogenomics in Zimbabwe
No full textThe potential of pharmacogenomics (PGx) to positively impact health outcomes and quality of healthcare is well-established. However, the application of available evidence into clinical practice is still limited due to limited knowledge among healthcare professionals, including pharmacists. As a start towards building capacity for PGx education, we assessed knowledge, attitudes, and perceptions about PGx among practising pharmacists and pharmacy students. A cross-sectional study was conducted among pharmacists and undergraduate pharmacy students selected using a convenient sampling method—a 37-question survey instrument was used to obtain information regarding PGx among the participants. Out of a total of 131 participants, 56% of respondents showed fair-to-good PGx knowledge. Respondents’ self-reported assessment indicated that 88% had average and above knowledge scores in PGx. Practising pharmacists in Zimbabwe have positive attitudes towards PGx and would support its application to improve treatments. However, there were concerns about security and discrimination when genomics data is used by those who do not understand its meaning. Participants agreed that they would play a leading role in PGx testing if provided with appropriate training. The interest in PGx is challenged by their limited knowledge and understanding of genetics, suggesting a need to update curricula for pharmacy students and for continuing health education programmes
Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.
No full textAfrica is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease
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