Grace Koo

Grace, a sophomore studying Data Science & Statistics and Business Analytics at Miami University, investigated genetic variations that led to high-altitude hypoxia adaptation in Ethiopians in the context of reproductive fitness

High-altitude adaptation to hypoxia has occurred in Tibetans, Andeans, and Ethiopians populations which have resided at >2,500m elevation for many generations. I truly had a phenomenal summer at the Broad. I felt deeply supported and embraced by a community that believes in me. The BSRP equipped me with the resources, mentality, and skills needed not only to be a great scientist, but also an individual who is well rounded, curious, and a leader. This program gave me clarity in my interests and confidence in my abilities while stretching me and shaping me. I am so grateful and honored to have been a part of this program.These adaptations protect against reproductive health issues like preeclampsia and low birth weight. Ethiopians have convergently adapted to high altitude, with distinct oxygen uptake or delivery mechanisms that are poorly understood. Our study aims to uncover genetic adaptations to hypoxia in Ethiopians and characterize their roles in hypoxia-related pregnancy and birth complications. We recently sequenced over 43,000 participants across Ethiopia, Kenya, South Africa, and Uganda using a novel "Blended Genome Exome'' (BGE) approach, which sequences genomes at low coverage (2-3X) and exomes at higher coverage (30-40X). By integrating  geographical data, we compared the genomes of 9,274 Ethiopian highlanders with 11,788 Ugandan and Kenyan lowlanders. We are scanning for positive selection signatures by combining multiple statistical tests using the SWIF(r) machine learning method. Furthermore, we are overlapping these regions with genetic variants associated with maternal and fetal health outcomes to determine which of these may impact reproductive functions. Then, we will conduct enrichment analysis using functional annotation to better unravel the mechanisms by which genetic adaptations affect reproductive fitness. Ultimately, our findings will inform molecular mechanisms that contribute to hypoxia resilience, potentially nominating therapeutic targets to mitigate hypoxia-associated pregnancy complications. 

Project: Genetic adaptations to High-Altitude Hypoxia in Ethiopian Populations and Their Impact on Reproductive Fitness

Mentor: Yue Shi, Martin Lab, Stanley Center for Psychiatric Research