This award was provided as part of NSF's Social, Behavioral and Economic Sciences Postdoctoral Research Fellowships (SPRF) program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from underrepresented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. Over 140 million people live in high altitude zones around the world and are susceptible to chronic or temporary disorders related to low oxygen concentrations (hypoxia). Reproductive disorders exacerbated with hypoxia include preeclampsia, which complicates 2-10% of all pregnancies worldwide, causes nearly 40% of all premature births and is associated in 10-15% of maternal deaths. Previous research has shown that native Andean populations carry unique genetic variants conferring adaptation to high altitude hypoxia. Some of this genetic variation may also underlie susceptibility to preeclampsia, and therefore may influence human reproductive fitness. This investigation characterizes genetic structure and adaptation in native populations from the Peruvian Andes to understand the genetic factors influencing human reproduction in challenging environments. Characterizing underlying genetic diversity and population history is essential for the identification of functional genetic variants, therefore this work will examine how past demographic processes in the region have shaped the genomes of indigenous Peruvians. This project is conducted in collaboration between USA (Arizona State University, Stanford University), Mexico (National Laboratory of Genomics for Biodiversity), and Peru (Puno Regional Hospital) based research teams. A crucial benefit of this opportunity is to increase representation of Latinos in genomics, promote international collaborative research, strengthen genomics research capacity within Latin America and further education through training and outreach. The project is led by a postdoctoral researcher underrepresented in the SBE sciences, and further broadens participation of underrepresented groups in the sciences by training Latin American graduate students. The genetic data produced by this project will be freely available upon completion, contributing to lessen the underrepresentation of ethnically diverse populations in human genomics research.
The Peruvian Andes was home to multiple major civilization centers of the pre-contact Americas, and contemporary peoples in this region retain a large reservoir of Native American genomic diversity. Because they have evolved adaptations to the extreme conditions of high altitude hypoxia, understanding the ancestry and evolution of native Andeans can lead to discovery of genetic loci involved in human adaptation for successful reproduction in low-oxygen environments. Thus, this investigation examines fine-scale patterns of genetic diversity in native Andeans to: (1) characterize their demographic history, (2) identify candidate loci under natural selection, and (3) understand how genomic architecture and admixture influence preeclampsia susceptibility and reproductive fitness in a high altitude environment. Genotype data from 17 native populations from the coastal, highland and lowland Andes (N=170) will be generated and analyzed to characterize local patterns of genetic diversity. Additionally, existing genotype data from Andean families suffering from preeclamptic pregnancies in Puno, Peru (N=530) will be analyzed by mapping associations between genetic variants, ancestry and preeclampsia phenotype. Studying human groups with unique genetic adaptations facilitates identification of the primary genetic factors underlying complex phenotypes and gene function. This research examines Andean groups as a model to understand human physiology in hypoxic conditions. This natural experiment provides an excellent opportunity to understand the genetic factors influencing human reproductive fitness in challenging environments.
