1. Native American Genome Diversity
Native American populations are the human group less studied as regards its genetic variability. Although the few studies using genomic array had helped to understand the Native American populations’ structure better, the genotyping platforms of this technique are based on the existing genetic variation of African, Asian and European populations, not taking into account the Native American variability, precisely because of the lack of reference genomes to be used. This lack of information has significant implications in medical studies since most of the studies of case-control performed today are done with conventional arrays, that are not suitable for studies in populations that exhibit large Native American component, like Mexicans, Peruvians, and individuals from some regions of Brazil. The 1000 Genomes Project does not include the study of Native American populations, further increasing the neglect in the genetic information about these people. This project aims to fill this gap sequencing of 150 complete genomes of Native American populations in order to unlock the full genomic variability of these populations, establish the evolutionary processes involved in the generation and maintenance of this diversity, and assist in the development of high-fidelity methods for clinical studies involving admixed and Native American populations
2. DNABr (DNAdoBrasil): exploring genetic admixture for medical and evolutionary research.
The admixture of the Brazilian population is unique due to the strong presence of three parental groups – Native Americans, Europeans, and sub-Saharan Africans (both East/West African), resulting in a highly genetically heterogeneous population. However, Brazilian genetic variation remains poorly investigated. We propose sequencing samples from the Longitudinal Study of the Adult Health (ELSA-Brasil), the largest ongoing prospective study in the Brazilian population. Since 2008, ELSABrasil has studied 15,000 individuals from different regions of Brazil to understand the development and progression of chronic diseases – in particular, obesity, cardiovascular diseases, and diabetes. Data collected comprise more than 3,000 phenotypes, including semi-structured interviews, clinical exams, anthropometry, and craniometry. An ancestry study revealed the tri-hybrid nature of the ELSA sample (23% African, 18% Native American and 59% European ancestry). We will catalog and analyze genetic variation through whole-genome sequencing of this cohort to address questions of population history as well as genetic architecture underlying complex traits. We have key aims: (1) to increase the representation of non-Europeans and non-Asians in genomic research; (2) to understand phenotypic impacts of genetic variants within an admixed population; (3) to understand demographic and evolutionary processes shaping the Brazilian population.
3. Genomic and epidemiological aspects of the COVID-19 in native Brazilian populations
The Native American populations are, since the first contact with Europeans, exposed to a myriad of pathogens from which they have been isolated for more than 15 centuries since their differentiation in Beringia. Examples abound of epidemics that plagued post-contact America, leading to the extinction of diverse native populations. Recent studies involving ancient and present-day individuals showed a decrease in genetic variability between 50% and 90% after the arrival of Europeans. The leading cause of death in Brazilian Natives today is respiratory complications in a consequence of infections. Therefore, given the current epidemic of COVID-19, it is crucial to study these historically vulnerable populations, contributing to a better understanding of the impact of disease outbreaks (past and present) on these populations, and investigating the existence of genetic differentiation in these individuals related to the evolution of SARS-CoV-2 infection. The present project intends to study COVID-19 under genomic and epidemiological aspects in 550 individuals belonging to two native populations, Tupiniquim and Guaraní-Mbyá, resident in Espírito Santo, with different levels of exposure to urban society. Given the extensive studies in these populations over the past decades, it will be possible to assess the evolution of the epidemic fully, whether the response is related to the genetic profile of these populations, and what the contribution of pre-existing clinical findings (i.e., tuberculosis, diabetes). Besides, it will be essential to transfer the findings in these native individuals to assess whether the potential for infection may be related to native ancestry in the Brazilian population.
4. Reconstructing South America Human History from paleogenomic data
The American continent was the last continent to be colonized by the human species, and how this settlement occured is still an intense debate in the scientific community. After entering the American continent, about 15,000 years before the present (YBP), the first Americans expanded rapidly, reaching South America around 12,000 YBP. The continuous occupation of the South American Atlantic coast begins during the Holocene (~ 11,500 YBP), a few thousand years after the human entrance in the continent. The populations that occupied this region, called Sambaqueiros, little is known about its evolutionary history and genetic proximity to the present Native American populations. The present project aims to investigate the population dynamics of the Brazilian coast settlement, as well as trying to establish the genetic relations between the paleo populations that inhabited this region and the current Native Americans. To do so, we will generate data from mitochondrial genomes and SNPs arrays from paleo individuals from Sambaquis and Native Americans from different populations belonging to several linguistic stocks.