TMC PULSE

t m c » p u l s e | m a y 7, 2 0 1 4 28 T he Human Genome Project, a 13-year project initiated by the National Institutes of Health (NIH), the Department of Energy and others, gave researchers an unprecedented under- standing of DNA and the sequencing of genomes. It helped develop new technologies for genomics research, and the role that research can play in treating, curing and preventing disease in populations worldwide. To date, the project has led to the discovery of more than 1,800 disease genes. In 2009, twenty years after the Human Genome Project was first pro- posed, the African Society of Human Genetics, NIH, and the Wellcome Trust, met in Cameroon to discuss issues sur- rounding genetics research in Africa. One issue of concern was the fact that the continent's genetic research was not keeping pace with the rest of the world, despite the tremendous need. Out of the Cameroon meetings emerged Human Heredity and Health in Africa (H3Africa), which seeks to study the connection between genet- ics and disease susceptibility and treatment in African populations. The multi-institutional effort houses the Collaborative African Genomics Network (CAfGEN), led by primary grant awardee Botswana-Baylor Children's Clinical Centre of Excellence (COE). CAfGEN and the other centers and projects under H3Africa aim to build a sustainable genomics research presence in Africa, beginning with training and infrastructure. "The whole problem is that the disease burden in the world is the com- plete opposite of where the majority of genomics research has been con- ducted historically. There is a massive imbalance," explained Graeme Mardon, Ph.D., professor of Molecular and Human Genetics at Baylor College of Medicine and a co-principal investiga- tor of CAfGEN. Mardon adds that for many decades, foreign researchers have typically con- ducted studies in developing countries by taking patient samples from African participants and then conducting the research in labs in the U.S. and Europe, with little scientific acknowledgment or transfer of expertise to the people in Africa. This, he says, is no longer a tenable model, and is something that the governments of African nations are actively opposing. "They want to do the research themselves," he said, "on their own people, for the diseases that are affect- ing their people." Genomics, the study of how a person's genes interact with each other and the individual's environment, holds promise for the treatment of complex diseases—those that are most likely a result of both genetic and environ- mental factors. If researchers are able to identify the genetic basis for the progression of HIV/AIDS in Africa, there is a greater chance of finding targeted treatments and therapies for the affected population. "For kids, when the mother is known to be infected, there is a certain prob- ability that she will pass that on to her child," said Mardon. "So when the child is born HIV positive, they immediately begin antiretroviral therapy, and for the most part, these medicines are effective. Teach a Man to Fish baylor college of medicine partners to help african researchers build a foundation for the continent's genomics research. As part of Human Heredity and Health in Africa (H3Africa), researchers with Baylor College of Medicine are partnering with universities in Uganda and Botswana to provide infrastructure and training for the continent's genomics research. (Credit: Smiley Pool) A relatively small number, however, still progress to AIDS. Then there is another group of kids who have never been given antiretroviral drugs due to public health policies and limited resources in the past, yet they will never get sick. They are resistant to the damaging effects of the virus. "There is quite a lot known in western Caucasian populations about what types of mutations can allow one to be resistant to HIV, but there is very little known in African countries, which is ironic because that is where the overwhelming majority of people in the world are infected with HIV. So we need to explore whether the same muta- tions that allow resistance to HIV in Caucasian populations are also present in African populations or if new ones can be discovered. "One of the most common and effec- tive mutations that confers HIV resis- tance in Caucasians has already been looked at to a limited extent, in African populations, and that mutation has not been found. So we need to take a closer look and see if there are other possible mutations in the same gene that could lead to resistance in some cases." Professor Gabriel Anabwani, principal investigator of CAfGEN and executive director of the Botswana- Baylor Children's Clinical Centre of Excellence explained the value of put- ting the research capabilities in the hands of African researchers. "Most of the previous genetic stud- ies in HIV, and in fact most genome- wide association studies in general, have been undertaken in non-African, adult populations," he said. "CAfGEN will address these disparities in genomic research. Indeed, there is a great need to study the genetic factors of disease progression in children because their disease differs consider- ably from their adult counterparts and they potentially have more to gain from therapeutic advances." B y A m a n d a D . S t e i n

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