Dr Marlo Möller
Researcher: Department of Biomedical Sciences
Division of Molecular Biology and Human Genetics
Faculty of Medicine and Health Sciences
DST-NRF Centre of Excellence in Biomedical Tuberculosis Research
South African Medical Research Council Centre for Tuberculosis Research
Dr Möller is in the Department of Biomedical Sciences, Stellenbosch University, South Africa. She has worked in the field of human genetic susceptibility since 2004. Her investigations of the genetic contribution of the human host to individual and population susceptibility to tuberculosis include tuberculous meningitis, tuberculosis resisters, the role of ancestry in tuberculosis disease and primary immunodeficiencies.
Title of the talk: Connections between Ancestry, Genes and Tuberculosis
DST-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
The ancient disease of tuberculosis (TB) is still the chief cause of death in many areas, with Africa home to most high burden countries. To find the genetic underpinnings of TB, we have studied the complete susceptibility spectrum, from individuals with rare susceptibility mutations to common genetic variants in the general population, using association studies, genome wide linkage studies and genome-wide association studies to identify genes and loci that inform the variation in disease outcome between individuals. Most infected individuals develop latent TB infection: a positive tuberculin skin test (TST) but no disease symptoms. A new paradigm, the Resister phenotype,was found recently. A small fraction of the population living in a TB endemic area has a negative TST, which may indicate a genetic resistance factor. Individuals with primary immunodeficiency (PID) in high TB incidence communities in South Africa are often not detected. We have identified many mutations in PID patients using whole-exome sequencing, informing patient management. By focusing on recurrent TB cases, we hope to identify host based therapies. Our participants are predominantly from the Western Cape and investigating the ancestral population contributions of this complex five-way admixed population in nearly 1000 individuals showed an unexpectedly high KhoeSan input. Our first admixture mapping study of TB showed that KhoeSan ancestry is a major component of TB susceptibility. The varied HLA class I alleles in the population enabled a human gene- Mycobacterium tuberculosis strain interaction study, which could provide information about vaccine efficacy.