Generation of molecular-level data on the MHC loci using novel bioinformatic approaches: genomics and transcriptomics

• Grant number: 25/11787-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Erick da Cruz Castelli
• Grantee: Nayane dos Santos Brito Silva
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 21/14851-9 - Human Population Genomics: a view from admixed populations, AP.TEM

Abstract

Alignment bias is the central issue preventing correct SNP and haplotype calls in genes from the Major Histocompatibility Complex (MHC) when using NGS sequencing. Current datasets are biased regarding MHC variants, mainly in HLA genes. These unreliable genotypes and haplotypes may lead to incorrect conclusions regarding the evolutionary aspects of this important genomic region. Moreover, alignment bias also harms HLA expression level estimations in RNA-seq data. We aim to develop new algorithms and software to properly align short sequences from the MHC, allowing accurate detection of indels and SNPs, short structural variants, haplotypes, and expression estimates. The supervisor's group has developed methods for HLA class I genes used in many disease-association and genetic population studies. This project aims to update the existing approach to support HLA class II genes when evaluating DNA and RNA sequencing data. This new/updated method will be applied to detect any variant in the SNP and haplotype level across the MHC in more than 9,000 samples from worldwide populations, including Brazilians. These data will be used in downstream analysis, including an in-depth characterization of some MHC genes, how variants distribute across the globe, expression estimates in individuals carrying specific genotypes, and other applications.