Human Population Genomics: a view from admixed populations

• Grant number: 21/14851-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2023
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Diogo Meyer
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Erick da Cruz Castelli
• Associated researchers: Camila Ferreira Bannwart Castro ; Carla Luana Dinardo ; Celso Teixeira Mendes Junior ; Cibele Masotti ; Kelly Nunes ; Michel Satya Naslavsky ; PAULA FRAIMAN BLATYTA CASELLI ; Regina Célia Mingroni Netto
• Associated scholarship(s): 25/13658-1 - Technical support for Project: Implementation of IT infrastructure and process automation for human population genomics analysis, BP.TT; 25/15750-2 - Natural selection in the MHC region of human populations, BP.PD; 25/11787-9 - Generation of molecular-level data on the MHC loci using novel bioinformatic approaches: genomics and transcriptomics, BP.PD; 25/00828-6 - Population differentiation under strong selection: a case study with HLA loci, BP.DD; 24/05419-4 - Decoupling between sickle-cell disease and african ancestry in Brazil, BP.IC

Abstract

Admixture among populations produces genomes that are a mosaic of different ancestries. This mixing can originate novel genetic combinations, which are the potential substrate for adaptive evolution and can also modulate phenotypes, including diseases. As a consequence, understanding the genetic consequences of admixture is of both evolutionary and biomedical interest. Here, we investigate the genetics of admixed populations with an emphasis on two aspects: the role of admixture on Brazilian populations, and its impact in two genomic regions involved in immunity and human health: the Major Histocompatibility Complex (MHC) and the Leukocyte Receptor Complex (LRC). Our research is structured around three main themes. First, we propose to develop bioinformatic tools to solve the problems of alignment bias and genotype calling, which are common in the MHC and LRC regions. We will then apply these tools to large samples of sequenced genomes, including admixed Brazilians, documenting the diversity of these genomic regions and discussing the effects of variation to gene function and transplantation. Second, we will use the newly generated data to investigate how natural selection has shaped differences among populations in the MHC and LRC, and will test whether recent admixture increases diversity in these immunity-related genes. Third, we will investigate how admixture contributes to the prevalence of deleterious and disease-causing alleles throughout the genome. We will specifically investigate the severity of sickle-cell disease, the most common Mendelian disease in Brazil, which was originally associated with African ancestry genomes but has become increasingly present in genomes with extensive non-African ancestry. Our research will contribute to an understanding of how admixture is shaping genomic diversity in Brazilians, and will highlight the consequences of this process to genes involved in immunity. Our findings will be relevant to the understanding of evolutionary processes and biomedical applications, and will broaden our understanding of genetic diversity in understudied populations. (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)

CIRIACO, VIVIANE APARECIDA DE OLIVEIRA; RODRIGUES, AMANDA MUNIZ; TIBURCIO, BRENDA CAROLINE DA SILVA; SILVA, JOYCE MACHADO; NALAVSKY, MICHEL SATYA; MENDES-JUNIOR, CELSO TEIXEIRA; CASTRO, CAMILA FERREIRA BANNWART; CASTELLI, ERICK C.. The MICA deletion across different populations. HUMAN IMMUNOLOGY, v. 85, n. 6, p. 9-pg., 2024-11-20. (21/14851-9, 21/13672-3)

CASTELLI, ERICK C.; PEREIRA, RAPHAELA NETO; PAES, GABRIELA SATO; ANDRADE, HELOISA S.; FERREIRA, MARCEL RODRIGUES; SANTOS, ICARO SCALISSE DE FREITAS; VINCE, NICOLAS; POLLOCK, NICHOLAS R.; NORMAN, PAUL J.; MEYER, DIOGO. kir-mapper: A Toolkit for Killer-Cell Immunoglobulin-Like Receptor (KIR) Genotyping From Short-Read Second-Generation Sequencing Data. HLA, v. 105, n. 3, p. 14-pg., 2025-03-01. (21/14851-9)

SILVA, NAYANE S. B.; BOURGUIBA-HACHEMI, SONIA; CIRIACO, VIVIANE A. O.; KNORST, STEFAN H. Y.; CARMO, RAMON T.; MASOTTI, CIBELE; MEYER, DIOGO; NASLAVSKY, MICHEL S.; DUARTE, YEDA A. O.; ZATZ, MAYANA; et al. A multi-ethnic reference panel to impute HLA classical and non-classical class I alleles in admixed samples: Testing imputation accuracy in an admixed sample from Brazil. HLA, v. 103, n. 6, p. 12-pg., 2024-06-01. (21/02815-8, 21/14851-9)