New methods of DNA sequencing have produced a great abundance of DNA sequences from humans and many other species, including species now extinct. The proposed research will be intended to help analyze and interpret DNA sequence data both for understanding basic genetic processes such as natural selection and recombination and for understanding the history of humans and the genetic basis of inherited diseases. The proposed research is in four areas: (i) the analysis of DNA sequence data from Neanderthal bones for the purpose of understanding the relationship between Neanderthals and modern humans and for understanding the recent history of modern humans since their separation from Neanderthals, (ii) the prediction of patterns in gene frequencies in populations that have undergone a recent range expansion, with particular emphasis on past range expansions of modern humans populations in Europe, Asia, and the Americas, (iii) the analysis of DNA sequences of bacterial species obtained in samples from extreme environments, for the purpose of quantifying the extent of genetic recombination and differentiation between different strains, (iv) modeling the genetic basis of complex inherited diseases such as schizophrenia, many cancers, and type 1 and 2 diabetes, for the purpose of quantifying the interactions among genes that create higher risk and for devising new methods for identifying genes associated with higher risk. Although the goals of the four areas are somewhat different, similar mathematical and statistical methods will be used in each. Models of population genetic forces, including natural selection, recombination, genetic drift and migration will be developed and tested against available data. Computer simulations of those models will be used to generate hypothetical data sets for testing proposed statistical methods.

Public Health Relevance

Diseases, such as cancer, heart disease, and diabetes, that are partly inherited yet are not caused by defects in single genes, are the leading cause of mortality in the US and other developed countries. The proposed research will develop mathematical and statistical tools that will help with understanding the genetic basis of such diseases, both by improving the understanding of the history of modern humans and by finding new ways to identify genes causing a higher risk of such diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040282-25
Application #
8311723
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
1988-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
25
Fiscal Year
2012
Total Cost
$281,222
Indirect Cost
$92,759
Name
University of California Berkeley
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Racimo, Fernando; Schraiber, Joshua G (2014) Approximation to the distribution of fitness effects across functional categories in human segregating polymorphisms. PLoS Genet 10:e1004697
Schraiber, Joshua G (2014) A path integral formulation of the Wright-Fisher process with genic selection. Theor Popul Biol 92:30-5
Fu, Qiaomei; Li, Heng; Moorjani, Priya et al. (2014) Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514:445-9
Lazaridis, Iosif; Patterson, Nick; Mittnik, Alissa et al. (2014) Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature 513:409-13
Macholdt, Enrico; Lede, Vera; Barbieri, Chiara et al. (2014) Tracing pastoralist migrations to southern Africa with lactase persistence alleles. Curr Biol 24:875-9
Prufer, Kay; Racimo, Fernando; Patterson, Nick et al. (2014) The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505:43-9
Slatkin, Montgomery (2013) A method for estimating the effective number of loci affecting a quantitative character. Theor Popul Biol 89:44-54
Landis, Michael J; Schraiber, Joshua G; Liang, Mason (2013) Phylogenetic analysis using Levy processes: finding jumps in the evolution of continuous traits. Syst Biol 62:193-204
Rohlfs, Rori V; Murphy, Erin; Song, Yun S et al. (2013) The influence of relatives on the efficiency and error rate of familial searching. PLoS One 8:e70495
Schraiber, Joshua G; Mostovoy, Yulia; Hsu, Tiffany Y et al. (2013) Inferring evolutionary histories of pathway regulation from transcriptional profiling data. PLoS Comput Biol 9:e1003255

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