Genetic variability in HLA genes: from evolution to impacts on human health

• Grant number: 21/03099-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Heloísa de Souza Andrade
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Admixed populations are an important repository of evolutionary, demographic, and genetic information. Their study provides information about their history and evolutionary dynamics. In America, populations have predominantly European, African, and Native American ancestry. In addition to the contributions of admixture, natural selection and genetic drift have shaped population variability continuously over generations. To study the interactions between demographic e selective processes in admixed Brazilians, we propose an investigation of the strongly selected MHC region, where the HLA class I and II genes are located, and which plays a key role the immunological response to pathogens, neoplasias, and the definition of compatibility for transplantation. Previous studies have investigated the processes that shape both genomewide and MHC region variability in various populations, but few studies have addressed the microevolutionary processes that operate in admixed groups, such as Brazilians. Within this context, we aim to develop two sub-projects involving admixture and MHC diversity. The first will seek to understand how admixture impacts the chances of finding a compatible donor for bone marrow transplantation. We will investigate how increasing African ancestry and admixture reduce the chances of finding a potential donor. The second sub-project investigates a recurrent finding, which is the excess of African ancestry in the MHC region in admixed populations. We will seek to understand if the excess of African ancestry in the MHC region can be explained by recent selection favoring specific alleles of African origin, whether this process is explained by a coevolutionary process involving the interaction between HLA and KIR genes, and if other selective models explain the advantage of African HLA alleles in the context of admixture. Together, these projects help understand how admixture generates patterns of variation on which selection can act, how selection influences diversity in admixed populations, and how admixture influences an important medical issue, which is the chance to find compatible donors.