Genetic Susceptibility to Mycetomaadmin
GENETIC SUSCEPTIBILITY TO MYCETOMA IN SUDAN ENDEMIC AREAS
Rayan S. Ali1,3, Sahar Mubarak Bakhiet1,2*, Ahmed Hassan Fahal1, Muntaser E Ibrahim2, Melanie Newport3
1 The Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan.
2 Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
3 Brighton and Sussex Medical School, Brighton, UK.
*Corresponding author: Dr. Sahar Mubarak Bakhiet, Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, 11111 Khartoum, Sudan. P.O. box 102. email: email@example.com
Mycetoma is a neglected tropical disease affecting disadvantaged communities in tropical regions. Although exact prevalence data are not available, Sudan has one of the highest burdens of disease globally. The condition typically occurs following traumatic inoculation of the causative organism into the subcutaneous tissue but it is notable that not all individuals exposed to infection develop clinical disease. It is likely that there are multiple factors that contribute to this observation including those attributable to the environment and to the pathogen. There is also evidence that host factors may be important.
The aim of this study is to specifically investigate the role of host genetic factors in susceptibility to mycetoma.
DNA samples were collected from members of two families with multiple cases of mycetoma who live in Sinnar state (one of the highly endemic areas). DNA samples from 10 members of these families, representing a mix of affected and unaffected family members from both sexes was sent for whole exome sequencing (WES). WES and variant calling were both done by BGI® (Hong Kong, China).
WES variant prioritization and filtering was done based on the variants’ impact and their effect of on protein structure, function or expression. ClinVar database and Varsome impact analysis tool were used to detect variants related to clinical conditions.
WES variant analysis revealed functional variants in 3 candidate genes. To confirm the functionality of these variants, real-time PCR (RT-PCR) is now being performed to detect difference in gene expression, of the three candidate genes, between eumycetoma patients and healthy controls.
Based on the findings of this pilot study, we aim to expand the mycetoma genetics resources to the already established Mycetoma Research Centre (MRC) biobank to be used for family based WES and heritability estimation, and population based association studies.