262T Poster - Population Genetics
Thursday June 09, 8:30 PM - 9:15 PM

Authors:
Elise Kerdoncuff ^1,2; Laurits Skov ^1,2; Wei Zhao ³; Jennifer Smith ^3,4; Andrea Ganna ⁵; Sharon Kardia ³; Aparajit B. Dey ⁶; Jinkook Lee ⁷; Priya Moorjani ^1,2

Affiliations:
1) Department of Molecular and Cell Biology, University of California, Berkeley, United States of America; 2) Center for Computational Biology, University of California, Berkeley, United States of America; 3) Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America; 4) Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, United States of America; 5) Institute for Molecular Medicine Finland, Helsinki, Finland; 6) Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India; 7) Department of Economics, University of Southern California, United States of America

Keywords:
Population history

Previous genotyping surveys of India have shown that most present-day Indians have ancestry from two divergent ancestral populations: Ancestral North Indian (ANI) related to Central Asians and Iranians, and Ancestral South Indian (ASI) distantly related to the Andamanese group, Onge. This mixture is widespread with most groups deriving ~20-80% ASI ancestry in India. Ancient DNA data from Central Asia and South Asia has further shown that both ANI and ASI were in turn admixed and had ancestry from ancient groups of South Asian hunter-gatherers, Neolithic Iranian-farmers, and Steppe Pastoralists from Eurasia. These mixtures occurred in the past 8,000 years and are associated with the spread of Neolithic farming and Indo-European languages to South Asia. Following the admixture, India experienced a major demographic shift towards endogamy leading to strong founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. In this study, we generated ~3,000 whole genome sequences from India. Our study includes diverse ethno-linguistic groups from India, including samples from most geographic regions, speakers of all major language families and tribal and caste groups––providing a comprehensive coverage of genetic variation in India. Using these samples, we provide a detailed reconstruction of the history of India in the past 50,000 years. We examine the distribution of Neanderthal and Denisovan ancestry across regions and in relationship to other worldwide populations. We also study recent events providing new insights about the ANI and ASI mixture and its impact on disease and adaptation on the subcontinent. Finally, we investigate the signatures of founder events in India and uncover key population-specific variants associated to diseases. Together, these analyses provide a detailed view of South Asian history and disease.