Balancing selection and population differentiation on HLA genes

• Grant number: 13/12162-5
• Support type: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): September 16, 2013
• Effective date (End): March 15, 2014
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Débora Yoshihara Caldeira Brandt
• Supervisor abroad: Jérôme Goudet
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Local de pesquisa : Université de Lausanne (UNIL), Switzerland
• Associated to the scholarship: 12/22796-9 - Population differentiation on genes under strong balancing selection: a case study on the HLA genes, BP.MS

Abstract

Balancing selection is an important evolutionary process contributing to the maintenance of genetic diversity in populations. Several non mutually exclusive mechanisms may underlie balancing selection, including heterozygote advantage, frequency dependent selection and fluctuating selection. All of these mechanisms have been invoked to explain the high diversity of Human Leucocyte Antigen (HLA) genes, which are the most well established case of balancing selection in the human genome. Here, we propose an analysis of population differentiation on HLA genes. We expect this analysis to provide insights on how balancing selection acts on those genes, and on the general effect of balancing selection on the differentiation between populations. Specifically, we will test two contrasting perspectives on the effect of balancing selection at HLA on differentiation: (a) selection results in the maintenance of shared polymorphisms among populations, reducing differentiation; (b) selection results in the increase in frequency of locally adaptive variants, increasing population differentiation. To this end, we will analyze SNP data, comparing their population differentiation between HLA genes and other genomic regions, and we will also use simulations to compare different scenarios of balancing selection with respect to their effects on population differentiation. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRANDT, DEBORA Y. C.; CESAR, JONATAS; GOUDET, JEROME; MEYER, DIOGO. The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes. G3-GENES, GENOMES, GENETICS, v. 8, n. 8, p. 2805-2815, AUG 2018. Web of Science Citations: 3.

BRANDT, DEBORA Y. C.; AGUIAR, VITOR R. C.; BITARELLO, BARBARA D.; NUNES, KELLY; GOUDET, JEROME; MEYER, DIOGO. Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data. G3-GENES, GENOMES, GENETICS, v. 5, n. 5, p. 931-941, MAY 1 2015. Web of Science Citations: 33.