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H3africa Newsletter 2 August 2018 Newsletter Issue 6 A New Dawn for Genomics in Africa We all know about sickle cell disease which by Dwomoa Adu causes anaemia and episodes of bone pain. First published in Business Times Africa Some 20% of individuals in sub-Saharan Africa (http://businesstimesafrica.net/) (SSA) carry one copy of the sickle cell gene (haemoglobin S). Professor Charles Rotimi and Body tissues are made up of cells which contain colleagues from the National Institutes of DNA, the unique genetic material that carries Health in the USA have shown that the instructions or blueprint for all our body’s haemoglobin S (sickle cell trait) evolved some development and function. A genome is all our 7 300 years ago in SSA and because it protects genetic material. The human genome is made against fatal malarial infections increased in up of 23 pairs of chromosomes including the frequency. Individuals with two genes for sex chromosomes - male XY and female XX. haemoglobin S however develop sickle cell DNA is made up of building blocks called anaemia. nucleotides and these are wound up in a double helix. What is completely amazing is that these four nucleotides: A, T, G or C in combination In this issue: provide enough information for the body to ● A New Dawn for Genomics in Africa make any protein and to transmit information ●The H3Africa Whole Genome Study from one generation to the next, thus forming ● The Launch of GeneMAP the basis of heredity. For describing and ● Conversation with an Early-Stage Career PI explaining this amazing structure Watson and ● Genetics Teacher Workshop Crick at the Cavendish Laboratory in ● Young Researchers Forum Cambridge were awarded the Nobel Prize in ● The 11th H3Africa Consortium meeting 1962. Some 50 years later the whole human ● Training Corner genome was sequenced. Of importance, ● Publications from the Consortium sequencing the genome of Africans showed us to have the most complex arrangements and Editorial Team: confirmed that humanity originated from Michelle Skelton Harry Wedel Africa around 60 000 years ago. Dan Lackland Laura Povlich Jennifer Troyer Co-Editor: Rolanda Julius Editor-in-Chief: Busisiwe Mlotshwa www.h3africa.org 1 August 2018 Newsletter Issue 6 Similarly, individuals with variants in the gene the gene of the enzyme that metabolizes for glucose 6 phosphate dehydrogenase (G6PD) Codeine rapidly are found at high levels in are protected from fatal malaria but are also North Africans and Ethiopians who are more at risk of destroying their red blood cells and likely to develop side effects from this drug. It developing anaemia. A further example is the is not known whether the tragedy addiction to Apolipoprotein L1 gene (APOL1) which carries Codeine-containing cough syrups recently a type of cholesterol in the blood stream. reported in Nigeria and of the abuse of Recent studies show that variants in the APOL1 tramadol in Ghana may also have a genetic gene evolved in Africans some 10 000 years ago basis. because they protected our forebears from fatal sleeping sickness (Trypanosomiasis). Thus, sequencing of the human genome led to However, the same APOL1 gene variants genome-wide studies that have provided increase the risk of developing chronic kidney crucial information on the causes of disease. Some of these studies suggest new mechanisms disease in African Americans and in Africans. Evolution in our genes can lead to protection for disease causation that can lead to new and improved treatments. Few of these important against infectious diseases but by the law of unintended consequences can also lead to studies have been carried out in Africans. Currently, researchers and doctors know some completely unrelated disease. If we can understand how this occurs, then we can of the genetic changes that can cause disease, develop new ways of treatment. but they do not know all of the genetic changes that can cause disease. The ability to rapidly sequence the Ebola virus genome by Professor Christian Happi’s group By studying many different kinds of diseases through genomics we expect to identify some from Redeemer’s University in Nigeria provided critical insights that allowed the of the genetic changes associated with patterns of transmission of this virus to be diseases. Since we also will combine genetic tracked. Our genes also shape the ways we information with information about handle drugs, and this can lead to either environmental exposures and responses to drug inadequate effectiveness or side effects from treatments we can obtain a better the medication. This is called understanding of why some people fall ill and pharmacogenomics. An example of this is the respond differently to treatment. With such drug Efavirenz which is used to treat HIV knowledge, future treatments could infection. Variants in the gene for the enzyme potentially become customized to a patient’s unique genetic make-up. that metabolizes Efavirenz are found at high levels in some African populations and this An initiative by the USA National Institutes of leads to high levels of the drug and toxicity. Health, and the UK Wellcome Trust and the Other examples include the drug Codeine African Society of Human Genetics in 2012 which is metabolized into Morphine; variants in established the Human Heredity and Health in www.h3africa.org 2 August 2018 Newsletter Issue 6 Africa (https://h3africa.org/) initiative and H3Africa also strongly supports collaborations funded studies on the genetic basis of disease among scientists in Africa and outside. in Africa with over 100 million US dollars. Other Accordingly, H3Africa scientists have reached funders include the Bill & Melinda Gates out to scientists of African origin in the Foundation and the Alliance for Accelerating diaspora to collaborate with their colleagues in Excellence in Science in Africa (AESA). developing genomic research on the continent. There has also been a gratifying willingness of The major areas of H3Africa research include scientists in high income countries to stroke, septicemia, cardiovascular disease, collaborate in this endeavor. All of this means diabetes, sickle cell disease, cardiometabolic that the health of people in Africa will benefit disorders, trypanosomiasis, kidney disease, from the rapid advances in genomic medicine nasopharyngeal and respiratory disease, that are currently taking place. Crucial to tuberculosis, rheumatic heart disease, developing and sustaining genomic science in schizophrenia and inherited neurologic Africa is training and this is occurring at all the disorders. These research projects are levels that allow the development of research. underpinned by a bioinformatics network and biorepositories in Africa, reflecting the “…the future wellbeing of our interest of the program in improving research infrastructure in Africa. people requires funding from The H3Africa Consortium has already made a African governments to sustain huge impact on ways in which the ethical, legal and social implications of genomic research in the achievements made so far” Africa can be addressed. For example, H3Africa has engaged national research ethics The platform for genomics research has been boards of most African countries where there established in Africa, but the sustainability of are research projects. This has allowed the these projects is critically dependent on the establishment of important principles willingness of African governments to provide governing the autonomy of the research funding for this research. The US Precision subject. Similarly, wide-spread engagement of Medicine project plans to recruit one million the communities in which research is being subjects for genomic research. The UK has a undertaken has helped to refine the ethical 100,000 Genomes Project. The European Union principles of informed consent, issues of broad and China all have planned or ongoing genome consent for secondary studies and data and projects. The important benefits of genomics biospecimen sharing to ensure that local needs to the future wellbeing of our people require and issues relating to genomic research are funding from African governments to sustain addressed. the achievements made so far. We foresee a future in which Africa joins the genomic www.h3africa.org 3 August 2018 Newsletter Issue 6 revolution that promises to transform the way genomics. in which we understand and treat diseases that blight our people’s health. As datasets of available whole genome sequences were being assembled for the design of an efficient Africa-centric H3Africa- genotyping SNP array, the chip design team The H3Africa Whole Genome recognized these gaps and pressed for a set of Sequence Study high-coverage whole genome sequences (WGS) from the consortium to facilitate the design by Ananyo Choudhury and Neil Hanchard process. The Genome Analysis working group in The dataset and history turn contacted H3Africa Principal Investigators for potential samples to fill these gaps. Once Despite recent reductions in the cost of whole the list of potential samples was received, the genome sequencing and the increasing working group carefully scrutinized the popularity of large-scale genome-sequencing available genomic data and proposed the best projects, the genomic diversity of Africa - with samples to be sequenced, focusing on only a few hundred low coverage genomes in geographic regions and ethnolinguistic the public domain - remains highly under- groups that have not been surveyed or might represented. Moreover, samples that have differ significantly from existing datasets.
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