About This ProjectAdvanced genetic and genomic technologies promise to transform our understanding and approach to human health and disease.Using Next Generation (NextGen) sequencing technologies, we will be able to better understand the host genetic factors that influence HIV/AIDS and TB disease progression in under-studied populations, namely children living in Africa.
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What is the context of this research?
The Collaborative African Genomics Network (CAfGEN) was formed in response to a call by the Human Heredity and Health in Africa (H3Africa) Initiative, which aims to facilitate a contemporary research approach to the study of genomics and environmental determinants of common diseases with the goal of improving the health of African populations.
Note: CAfGEN is funded by NIH Grant Number 1U54AI110398-01A1, though NIH neither endorses nor supports our supplementary crowdfunding efforts. No NIH funds have been used to support our Experiment.com crowdfunding page, which is administered by our researchers at Baylor College of Medicine. Our PI is Prof. Gabriel Anabwani, at the Botswana-Baylor Children's Clinical Centre of Excellence, which serves as the coordinating center for CAfGEN.
What is the significance of this project?
Sub-Saharan Africa remains at the epicentre of global HIV, and some 2.3 million children under age 15 are infected by HIV, of whom 230,000 annually are likely to die from the progression of the disease to AIDS. Although significant progress has been made, HIV/AIDS and its associated co-morbidities still remain a significant cause of mortality and morbidity. Advanced genomics technologies promise to provide important pathophysiological insights that could have a significant impact on the disease. These technologies have been successfully utilized to study host genetic factors influencing the natural history of HIV infection among adults in Western countries, and have led to tangible returns in therapeutic advances. Conversely, data concerning host genetic factors that are important to the rate of disease progression among HIV-infected children in Africa remains sparse. The same holds true for studies of the host genetic factors underlying progression to active TB disease – HIV’s most common co-morbidity - in HIV-infected children. A core goal of CAfGEN is to become a major center for large-scale genomic studies of pediatric HIV and associated co-morbidities in sub-Saharan Africa.
Over the long-term, children stand to benefit the most from scientific advances arising from genetic studies, as they have more years to live and the most to contribute with this time. HIV-infected children differ from their adult counterparts in their mode of virus acquisition, disease progression, and immune response, which suggests that the findings from adults may not be easily translated to children. Ironically, given their under-representation, children may also have the most to contribute to genetics studies; whereas external influences that accumulate over time (such as diet and smoking) can play a major role in complex infectious traits, environmental effects are relatively less in children, suggesting that genetic effects are likely to play a more prominent role in disease variability. Studies of infectious diseases within the context of a still maturing immune system offer unique opportunities to make significant findings that can impact arguably the most vulnerable and most important group of individuals. The underrepresentation and potential impact of HIV-infected children in genomic cohorts of HIV is a major impetus for forming our collaborative network.
What are the goals of the project?
The mission of the Collaborative African
Genomics Network (CAfGEN) is “to create a collaborative, multi-disciplinary, multi-institutional, inter- and intra-country network of African scientists, clinicians, and researchers using genomics approaches to study gene/environment interactions for HIV/AIDS, its co-morbidities, and other diseases among diverse pediatric African populations.” To meet the attendant challenges of accomplishing this mission, we have assembled a highly collaborative, synergistic network of institutions. HIV infection and related sequelae are the central focus of CAfGEN; however, our broader goal is to empower investigators with a wide array of skills that are required to examine any clinical problem that would be suitable for a genomics approach. We envision a critical mass of well-trained, highly knowledgeable, African human geneticists and genomicists who have a broad spectrum of expertise, the knowledge and support to secure outside funding, the ability to educate future generations of researchers, and the experience to collaboratively empower clinicians and researchers in a multi-disciplinary manner.
A myriad of studies on the host genetics of HIV disease have been successfully undertaken, yet only a small handful have involved sub-Saharan Africans and even fewer still, children, who are known to have a disease progression profile that differs significantly from their adult counterparts. Host genetic factors influencing HIV disease progression in sub-Saharan HIV-infected children have not been studied. At our current level of funding, we are right on the statistical threshold of having enough power to identify new genes that determine if and how a child will progress to HIV or TB disease.By increasing the number of individuals that we analyze through additional funding for genomic sequencing, we are much more likely to be able to identify new host genetic factors that influence disease progression.For every $500 we receive, we will be able to conduct NextGen sequencing on one additional individual. For $25,000, we will be able to sequence 50 additional individuals, greatly increasing the power of our sample size to identify the genetic host factors influencing disease progression. This, in turn, will help us to better understand and treat infants and children infected with HIV/AIDS and tuberculosis and may provide key insights into the development of preventative and curative therapies.
For every $500 we receive, we will be able to conduct NextGen sequencing on one additional individual. For $25,000, we will be able to sequence 50 additional individuals, greatly increasing the power of our sample size to identify the genetic host factors influencing disease progression. This, in turn, will help us to better understand and treat infants and children infected with HIV/AIDS and tuberculosis and may provide key insights into the development of preventative and curative therapies.
Meet the Team
Team BioDr. Graeme Mardon received his B.S. in 1980 with a double major in Biology and Chemistry from Haverford College. Following a four-year research associate position with Dr. Harold E. Varmus studying the viral oncogene src at the University of California in San Francisco, Dr. Mardon began graduate school at the Massachusetts Institute of Technology in 1984. He received his Ph.D. in 1990 in the laboratory of Dr. David C. Page where he studied genes located in the sex-determining region of the mouse Y chromosome. Dr. Mardon joined the faculty at Baylor College of Medicine in 1994 where he has established a research program studying the molecular genetics of developmental neurobiology using both the fruit fly Drosophila and the mouse as animal model systems. Over the last decade, Dr. Mardon has employed genomics approaches to study retinal development in Drosophila and humans and more recently to study TB and AIDS in African children.
Dr. Graeme Mardon received his B.S. in 1980 with a double major in Biology and Chemistry from Haverford College. Following a four-year research associate position with Dr. Harold E. Varmus studying the viral oncogene src at the University of California in San Francisco, Dr. Mardon began graduate school at the Massachusetts Institute of Technology in 1984. He received his Ph.D. in 1990 in the laboratory of Dr. David C. Page where he studied genes located in the sex-determining region of the mouse Y chromosome. Dr. Mardon then conducted his postdoctoral work with Dr. Gerald M. Rubin at the University of California in Berkeley from 1990 to 1994 studying genes required for normal eye development in the fruit fly Drosophila melanogaster. Dr. Mardon joined the faculty at Baylor College of Medicine in 1994 where he has established a research program studying the molecular genetics of developmental neurobiology using both the fruit fly Drosophila and the mouse as animal model systems. Over the last decade, Dr. Mardon has employed genomics approaches to study retinal development in Drosophila and humans and more recently to study TB and AIDS in African children.
Ever since I can remember I have been fascinated by the factors that determine heredity. I learned later that these are called genes in English. Born in rural colonial Kenya in 1948, I graduated from the University of Nairobi medical school in 1975 and later earned a Master of Medicine degree in pediatrics, completed a British Council Fellowship in pediatric cardiology at the Royal Hospital for Sick Children in Glasgow, UK and a Master of Science in Clinical Epidemiology at McMaster University, Canada. I taught pediatrics at the University of Nairobi and at Moi University in Kenya before relocating to Botswana in 1997. Since then I became deeply involved in the care of children living with HIV as this disease had become the major killer of children in Botswana and indeed in sub-Sahara Africa. Working with colleagues at Baylor College of Medicine, we established the Botswana-Baylor Children's Clinical Centre of Excellence, the first free standing pediatric HIV care clinic in Africa in 2003. We are now interested in understanding why some children who are infected with HIV progress rapidly to AIDS and death while others survive for many years without clinical evidence of disease. Similarly, some children who are co-infected with tuberculosis progress rapidly why others do not. Is there a genetic explanation for this? Understanding the genetic basis for these phenomena opens many therapeutic possibilities. That is why we have formed CAfGEN - a Collaborative African Genomics Network to spearhead this research.
Chester Wayne Brown
Over the past 2 decades I have been exploring the mechanisms by which genes either cause or influence human disease. Our technologies have now reached a point that these questions can be addressed directly in patients. This gives us the best chance to find answers that will lead to better tools to make early diagnoses and perhaps better treatments for HIV, tuberculosis and many other diseases. CAfGEN seeks to do both of these things through our research projects, while simultaneously empowering scientists in Africa to carry out these and related studies on their own populations now and well into the future. Achieving these goals will require rigorous training experiences, developing educational programs in genomics in African universities, and providing the necessary technologies and infrastructure in Africa to sustain independent, large scale genomics research projects. Because of the rich genetic diversity of the peoples of Africa and the overwhelming burden of disease, particularly in children, African populations have both the most to contribute and the most to gain from our understanding of the genetic basis of human disease.
Neil A Hanchard
I am a pediatrician and clinical geneticist originally from the sunny island of Jamaica. Through a series of serendipitous events after completing med school, I ended up in the world of genetics, and lo' and behold - I really liked it! Ever since, I've been trying to meld genetics with both the rare and the common diseases that I learned about in med school, particularly in under-represented populations.
Ed Pettitt received his Bachelor of Science degree in Human Biology from Cornell University and is currently completing graduate work in Healthcare Management and Global Health at The University of Texas School of Public Health. Mr. Pettitt works as a Senior Project Coordinator for the Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children's Hospital (BIPAI) and Collaborative African Genomics Network, where advises on best practices in adolescent medicine and healthcare transition and is helping to launch Africa's first collaborative pediatric genomics initaitive in Botswana and Uganda. Mr. Pettitt has served as an HIV/AIDS technical expert for WHO, UNICEF, USAID, and FHI 360, and is co-founder of the Houston Global Health Collaborative. Mr. Pettitt has also been recognized as an Albert Schweitzer Fellow for Life and a Rotary International Paul Harris Fellow.
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