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Genetic load and efficacy of selection on admixed populations

Grant number: 18/05500-5
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): July 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Diogo Meyer
Grantee:Jônatas Eduardo da Silva César
Supervisor abroad: John Novembre
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Chicago, United States  
Associated to the scholarship:15/19990-6 - Uncovering rare variants in HLA genes: evolutionary analysis and impact on genetic load, BP.PD

Abstract

To understand the interplay between demographic and selective processes inshaping genetic variation, two key quantities of interest are genetic load andthe efficacy of selection, which is the contribution of selection to the rateof change of the genetic load. Demographic processes such as population splits,bottlenecks and population growth can bring about changes in the magnitude ofgenetic load and efficacy of selection. For humans, an emerging consensus isthat among population differences in genetic load are likely to be small, whiledifferences in the efficacy of selection may be large, with African populationshaving the highest estimated efficacy of selection. Admixture processes, onthe other hand, can increase the genetic load and efficacy of selection abovenaive expectations and are still not completely understood.Given the increasing importance of admixture in shaping the genetic variationof future human generations, we propose to theoretically and computationallyinvestigate the genetic load and efficacy of selection of admixed populations.We aim to extend existing analytical treatments of load and efficacy ofselection to models involving arbitrary numbers of populations and rates ofadmixture. We will also quantify the magnitude of load and efficacy ofselection in various admixed populations, including those present in the 1000Genomes and a dataset of 1320 admixed Brazilian individuals of the AbraOMproject. This study will be carried out in collaboration with Prof. JohnNovembre who is a member of the Department of Human Genetics of the Universityof Chicago and an expert in the fields of genetic load and admixture of humanpopulations. (AU)

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