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)
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