About This Project

Ask the Scientists

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.