Mixture between populations is a fundamental process that shapes biology, genetic variation, and the risk for disease. Despite its importance, the analytical methods that are available to study mixture on a genome-wide scale are limited. This makes it a priority to develop methods that can analyze this history in the large data sets that are now practical to generate. No federal grant currently supports the development of such methods. This grant proposes to develop methods and make software available for studying mixture.
The Aims are: (1) To develop tools that make inferences about mixture based on allele frequency and haplotype frequency differences. (2) To develop tools that estimate dates of mixture based on admixture linkage disequilibrium and genetic divergence data. We expect that this grant will be of value in three areas. (a) It will support the development of methods and user-friendly software that will be important for evolutionary and medical genetics. (b) It will support work that will result in insights relevant to finding disease genes in human populations that are recently or anciently admixed. (c) It will lead to new insights about human history as well as the history of other organisms. The connection to medical genetics is particularly important. Our laboratory's past work on the evolutionary history of populations has been intertwined with our work on disease gene mapping, and the approaches that we developed in both areas were synergistic. In particular, we have leveraged the history of admixture in human populations to make new gene discoveries and to understand variation in disease risk across populations. We expect to be able to make further connections between evolutionary and medical genetics by developing sophisticated approaches for understanding and modeling population mixture.

Public Health Relevance

The history of population mixture is of importance to public health because it determines the genetic variants that individuals and populations inherit, which in turn make some people more or less susceptible to disease. In the last decade, it has become clear that many human populations are the result of mixtures of populations with divergent ancestries: not only African Americans and Latinos, but also South Asians and all non-Africans (who have Neandertal genetic material). For example, our group has developed methods for studying population mixture and directly applied them to discover genetic risk factors for prostate in African Americans. This grant proposes to develop sophisticated methods to understand and quantify mixture in human populations using modern genomic data. We anticipate that a deeper understanding of human population mixture will assist in the development of more powerful methods to discover genetic risk factors for disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM100233-04
Application #
8881218
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2012-05-01
Project End
2016-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
4
Fiscal Year
2015
Total Cost
$233,068
Indirect Cost
$95,565
Name
Harvard Medical School
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Harney, Éadaoin; May, Hila; Shalem, Dina et al. (2018) Ancient DNA from Chalcolithic Israel reveals the role of population mixture in cultural transformation. Nat Commun 9:3336
Mittnik, Alissa; Wang, Chuan-Chao; Pfrengle, Saskia et al. (2018) The genetic prehistory of the Baltic Sea region. Nat Commun 9:442
Olalde, Iñigo; Brace, Selina; Allentoft, Morten E et al. (2018) The Beaker phenomenon and the genomic transformation of northwest Europe. Nature 555:190-196
Lipson, Mark; Skoglund, Pontus; Spriggs, Matthew et al. (2018) Population Turnover in Remote Oceania Shortly after Initial Settlement. Curr Biol 28:1157-1165.e7
Palkopoulou, Eleftheria; Lipson, Mark; Mallick, Swapan et al. (2018) A comprehensive genomic history of extinct and living elephants. Proc Natl Acad Sci U S A 115:E2566-E2574
Loreille, Odile; Ratnayake, Shashikala; Bazinet, Adam L et al. (2018) Biological Sexing of a 4000-Year-Old Egyptian Mummy Head to Assess the Potential of Nuclear DNA Recovery from the Most Damaged and Limited Forensic Specimens. Genes (Basel) 9:
Lipson, Mark; Cheronet, Olivia; Mallick, Swapan et al. (2018) Ancient genomes document multiple waves of migration in Southeast Asian prehistory. Science 361:92-95
Posth, Cosimo; Nakatsuka, Nathan; Lazaridis, Iosif et al. (2018) Reconstructing the Deep Population History of Central and South America. Cell 175:1185-1197.e22
Mathieson, Iain; Alpaslan-Roodenberg, Songül; Posth, Cosimo et al. (2018) The genomic history of southeastern Europe. Nature 555:197-203
Unterländer, Martina; Palstra, Friso; Lazaridis, Iosif et al. (2017) Ancestry and demography and descendants of Iron Age nomads of the Eurasian Steppe. Nat Commun 8:14615

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