Analysis of HLA gene expression and investigation of the genetic architecture of regulatory control

• Grant number: 13/22007-7
• Support Opportunities: Scholarships abroad - Research
• Effective date (Start): October 21, 2013
• Effective date (End): February 20, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Diogo Meyer
• Host Investigator: Emmanouil Dermitzakis
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Université de Genève, Switzerland

Abstract

The classical HLA class I and II genes are highly polymorphic loci, for which there is ample evidence of balancing selection. Evolutionary studies have focused on the coding variation of these genes, which affects the protein structure of HLA molecules, and is the target of natural selection. However, there is comparatively less understanding on how expression patterns of these genes varies among individuals, populations and tissues. In addition, evolutionary studies have not accounted for information regarding variation in the level of expression. In the present study I propose to establish a methodology to quantify the expression of HLA genes using RNAseq. This method is the most reliable means of quantifying the abundance of transcripts from a specific tissue. The main difficulty in the application of RNAseq to the HLA data is that mapping transcripts to the reference genome. This arises because the high polymorphism at these genes makes it likely that the reference genome will differ from an individual's transcript at many sites, increasing the likelihood of mismatches, which render the transcript "unaligned". I propose a method to circumvent this difficulty, allowing an estimate of HLA expression. I propose the use of this data to identify expression QTLs (genetic variants that regulate gene expression) , and discuss how the identification of these may help in understanding the genetic architecture underlying the regulatory control at this locus, and how it experiences natural selection. (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)

AGUIAR, VITOR R. C.; CESAR, JONATAS; DELANEAU, OLIVIER; DERMITZAKIS, EMMANOUIL T.; MEYER, DIOGO. Expression estimation and eQTL mapping for HLA genes with a personalized pipeline. PLOS GENETICS, v. 15, n. 4, APR 2019. (12/18010-0, 15/19990-6, 16/24734-1, 13/22007-7, 14/12123-2)