Global genetic diversity assessment of the AIRE gene and association study with vitiligo in a sample of the brazilian population

• Grant number: 24/13641-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Eduardo Antônio Donadi
• Grantee: Pedro Mendes Laprega
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Human genetic diversity and its impact on gene products is one of the most central themes in biology, considering its implications for evolutionary history and health. Thus, a detailed characterization of this variability is of great interest to assist in scientific advancement, especially regarding genes associated with important physiological processes. Among them, the AIRE gene plays a central role in the process of immune self-tolerance, which is essential for the prevention of autoimmune conditions such as vitiligo. However, little is available on the general aspects of the diversity of this gene, especially considering the analysis of massive parallel sequencing data and in a Brazilian context. Therefore, it is intended to meticulously characterize global genetic variants in relation to alleles of variation sites and haplotypes of regulatory and coding regions, seeking to identify signatures of natural selection shaping the genetic diversity of such regions. This will be done using (a) large-scale genotyping data from a sample of 513 Brazilians, of which 68 have vitiligo, obtained through the MEGA array (Illumina) and whole genome imputation, and (b) 4131 individuals from two global genetic diversity databases, The 1000 Genomes Project and the Human Genome Diversity Project. With this in mind, it will be possible to conduct a case-control association study of the AIRE gene with this autoimmune pigmentation disorder for this population using a logistic regression method, adjusted for the effects of global and local genomic ancestry (ancestral origin of each haplotype of the AIRE gene) of each individual in the admixed sample.