Decoupling between sickle-cell disease and african ancestry in Brazil

• Grant number: 24/05419-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• Status: Discontinued
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Pedro Nicésio do Amaral
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/14851-9 - Human Population Genomics: a view from admixed populations, AP.TEM
• Associated scholarship(s): 24/23088-5 - Decoupling between sickle cell disease and African ancestry in Brazil: Deep Learning as a tool for understanding admixture dynamics and decoupling, BE.EP.IC

Abstract

Sickle cell disease is a heritable, monogenic blood condition with multisystem effects that affects more than 13 million people worldwide. Originating in Africa, most of the alleles causing the disease were introduced to Brazil during the colonial period, along with the forced migration of enslaved Africans. Since then, the combined effects of admixture and recombination have allowed alleles of African origin contributing to sickle cell disease to be transferred to chromosomes containing European and indigenous portions, among others. We refer to this process, in which a mutation originally present only in African chromosomes becomes progressively more associated with chromosomes of various ancestries, as "decoupling". Today, there remains a relevant positive correlation between an individual's global percentage of African ancestry and the presence of mutant alleles. It is expected that, over generations, admixture associated with recombination will be able to progressively break this correlation, generating a decoupling between the presence of the mutation resulting in sickle cell anemia and the individual's ancestry. Assortative mating is a demographic factor that can slow down decoupling, if spouses are more similar in terms of ancestry percentage than expected randomly. The present proposal aims to investigate how assortative mating impacts the decoupling process between African ancestry and being a carrier of mutant alleles, using genetic data and demographic data from IBGE to simulate how decoupling will occur in future generations.