Variant Bio and Wits University Launch Study to Explore African Genetics
Creation of a database of African genome variants aims to reveal how these variants may affect health
Variant Bio is excited to announce our second research project in South Africa through a collaboration with the Africa Wits-INDEPTH partnership for Genomics studies (AWI-Gen). With our partners, we are embarking on a project to understand how genes are regulated in different populations within South Africa, with the goal of improving our understanding of how genes affect health.
Gene regulation is the process of controlling which genes in a cell’s DNA are turned on and off. The process of turning on a gene to produce RNA and protein is called gene expression. Variation in gene expression represents an important dimension in understanding how populations vary at a biological level with significant implications for public health.
The ‘regulatory region’: Inside the genome
When we think of how a gene affects a person’s health, we usually think of the region of the gene that provides the instructions to create a protein. That part of the gene is called a “coding region.” However, these coding regions make up only a small part of the gene. Another part of a gene, called the “regulatory region,” is important in determining the amount of protein that is produced. You can think of these regions like a volume knob, turning a gene on or off, up or down. This can ultimately affect a person’s health, for example, by regulating cholesterol levels. Genetic variants in this regulatory region that increase or decrease how much of a gene is expressed are called “expression quantitative trait loci” (eQTL).
It is now becoming clear that many differences in human traits are the result of differences in gene expression levels that are controlled by eQTLs. Often, these genetic variants are not directly next to the gene they are turning on or off (in contrast to the example shown in the image above), making it difficult to determine exactly which variants control which gene.
In recent years, there have been important advances in our understanding of regulatory regions of the genome through the creation of eQTL databases, which combine genetic data with measurements of gene expression levels. However, those databases often only include data from people of European ancestry. There are very few databases of eQTLs that include individuals of African ancestry, and to our knowledge, none that are specific to South Africa. As more genetic studies are conducted in Africa, more and more genetic variation will be discovered and most of it will fall in regulatory regions. However, without knowledge of how it specifically affects gene expression levels, it’s difficult to interpret these discoveries, and in turn, apply them to healthcare.
To address this need, Variant Bio and the AWI-Gen Collaborative Centre at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) within the University of the Witwatersrand in Johannesburg (Wits) are partnering to create an eQTL database of information from South African individuals. The AWI-Gen Collaborative Centre is a Human Heredity and Health in Africa (H3Africa) Consortium study, led by Principal Investigator Prof. Michèle Ramsay. This project is a team effort, and includes researchers based throughout South Africa. Co-Principal Investigators include Prof. Stephen Tollman, based at The Wits/MRC Agincourt Health and Demographic Surveillance Site (HDSS) in Mpumalanga, Prof. Shane Norris, based at the Wits Developmental Pathways to Health Research Unit (DPHRU) in Soweto, Gauteng, and Mr. Solomon Choma, from the DIMAMO HDSS at the University of Limpopo, Limpopo. Variant Bio is uniquely suited to partner on this study, as our co-founder and Chief Technology Officer, Stephane Castel, was a lead analyst in the GTEx Project, the largest study of regulatory variants to-date, recently published in Science.
Prof. Ramsay at the SBIMB and her collaborators have visited the three participating study sites in Mpumalanga, Gauteng, and Limpopo to describe and solicit feedback about the study. As part of this community engagement, community members were shown a short video about the research being done in South Africa and what participating in these studies involves. You can watch the English version of that video below:
Understanding how genes are regulated is an important step along the path to eventually treating health problems that have a genetic basis. Through this collaboration, we hope to create an eQTL resource that can be employed by other researchers working to improve health in South Africa, and beyond.
