Understanding the human genome and its interplay with phenotypic variation requires studying the full spectrum of human diversity. In particular, populations from the American continent with Native American ancestry have been largely underrepresented in genomic studies, while they are bearers of a unique history from one of the regions of the world where proportionally more novel variation remains to be discovered.
We are interested in extending genetic research to diverse populations from the Americas to elucidate the evolutionary processes shaping Native American genomes, the historical and demographic events involved in the recent genetic admixture of the New World population, and its implications in health and disease.
Rare genetic variants are likely responsible for a disproportionate number of complex diseases and are likely to be population-specific. That being so, our current research projects are aimed at characterizing the extent of population substructure across the major regions of the Americas including Mexico, South America, and the Caribbean, as well as US-based communities tracing their ancestry to such regions.
We are accomplishing that in collaboration with multiple Institutions across the U.S. and Latin America, including the National Institute of Genomic Medicine in Mexico (INMEGEN), the National Institute of Medical Sciences and Nutrition in Mexico City (INNSZ), the National School of History and Anthropology (ENAH), the University of Guadalajara in Mexico, the National University of the Altiplano in Peru, the University of Puerto Rico in Mayaguez, the University of Miami, the University of California San Francisco (UCSF), and University College London (UCL). Together, we are generating genome-wide SNP array and full genome sequencing data to asses the degree of population structure among both Native American and admixed populations, including Hispanic/Latinos, African Americans and Afro-Caribbeans.
Understanding and quantifying the spectrum of functional variation in the human genome is a primary focus of both medical and population genomics. This variation is the result of numerous evolutionary and demographic processes that have shaped our genome over time, and better knowledge of these processes could help illuminate the origins and distribution of human disease. While many studies have used modern data to address these issues, with the recent application of next-generation sequencing technology to sequencing ancient genomes, we now have the tools to directly observe human genomes from key points in the past. These genomes can not only tell us about the demographic history of ancient human populations, but can also help us determine whether patterns of functional variation have changed over the last ~10,000 years of human population growth.
African populations maintain the highest levels of genetic diversity in the world and exhibit correspondingly high levels of phenotypic diversity. However, it is unknown if many of the same genes implicated in basic phenotypes such as height and skin pigmentation, which were initially ascertained in European cohorts, also contribute to phenotypic variation in Africa. Understanding the genetic basis of biomedical phenotypes in Africa provides a unique and potentially different perspective on the evolutionary history of human traits than biomedical efforts in European populations. We are currently involved in genomic sequencing of a diverse panel of populations throughout Africa, modeling the complex demographic history of migration throughout Africa, and the evolutionary history of biomedical traits like pigmentation and height.