Our research group tackles the following questions. What is the nature and extent of genetic variation within and between human populations? What are the biological and evolutionary processes that have produced the observed patterns of variation? How do genotypes contribute to phenotypes for complex traits (and how can we identify the relevant genetic variants)?
In our work, we develop new statistical methods for genetic analysis and also analyze data from humans and other organisms. Much of our statistical work makes use of computationally intensive approaches such as Markov chain Monte Carlo; these approaches can be effective for extracting subtle signals from large and complex data sets. In general, we aim to tackle problems where careful analysis, usually from a population genetic perspective, seems likely to yield new biological insights.
Currently, a central focus of the lab is on understanding how genetic variation drives variation in gene regulation within and between species. This work includes a mixture of data collection, computational analysis, development of statistical methods, and modeling of gene regulation. The project is a collaboration with Yoav Gilad and Matthew Stephens.
More broadly, the scope of our past and ongoing research includes work in the following areas: (i) methods for gene mapping of complex traits; (ii) inference of population structure from genetic data; (iii) history and structure of human populations; and (iv) genome variation and evolution; and (v) computational modeling of the controls of gene expression. We also distribute a number of programs and software packages, including the popular package structure for inferring population structure from genetic data ["Software" link above].
We are based in the Department of Human Genetics at the University of Chicago. Both our department, and the university in general, are very strong in population genetics, genetics of complex traits, and evolutionary biology. We are fortunate to enjoy especially close ties with the labs led by Yoav Gilad, Matthew Stephens, Molly Przeworski, Anna Di Rienzo, and Carole Ober.
Selected publications are listed below. For a more complete list see our Publications page, or look us up on Google Scholar or PubMed. In the list below, names of lab members are underlined for publications since the lab started in 2001. Our research has been funded by the Howard Hughes Medical Institute, the National Institutes of Health, the Packard Foundation, the Sloan Foundation, and Burroughs Wellcome Fund.
DNaseI sensitivity QTLs are a major determinant of human expression variation. Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ, Pickrell JK, De Leon S, Michelini K, Lewellen N, Crawford GE, Stephens M, Gilad Y, Pritchard JK. Nature. 2012 482:390-4. [PDF]
Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data. Pique-Regi R, Degner JF, Pai AA, Gaffney DJ, Gilad Y, Pritchard JK. 2011 Genome Research. 21:447-455. [PDF]
Understanding mechanisms underlying human gene expression variation with RNA sequencing. Pickrell JK, Marioni JC, Pai AA, Degner JF, Engelhardt BE, Nkadori E, Veyrieras JB, Stephens M, Gilad Y, Pritchard JK. 2010 Nature. 464:768-72. [PDF]
The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Pritchard JK, Pickrell JK, Coop G. 2010 Current Biology. 20:R208-15. [PDF]The role of geography in human adaptation. Coop G, Pickrell JK, Novembre J, Kudaravalli S, Li J, Absher D, Myers RM, Cavalli-Sforza LL, Feldman MW, Pritchard JK. 2009 PLoS Genetics 5:e1000500. [PDF]
High-Resolution Mapping of Crossovers Reveals Extensive Variation in Fine-Scale Recombination Patterns Among Humans. G Coop, X Wen, C Ober, JK Pritchard and M Przeworski. 2008. Science 319: 1395-1398. [PDF]
Sequencing and Analysis of Neanderthal Genomic DNA. JP Noonan, G Coop, S Kudaravalli, D Smith, J Krause, J Alessi, F Chen, D Platt, S Paabo, JK Pritchard, EM Rubin. 2006. Science. 314:1113-1118. [PDF]
DF Conrad, M Jakobsson, G Coop, X Wen, JD Wall, NA Rosenberg, JK Pritchard. 2006. A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nature Genetics. 38:1251-60. [PDF]
A high-resolution survey of deletion polymorphism in the human genome. D. F. Conrad, T D. Andrews, N. P. Carter, M. E. Hurles and J. K. Pritchard 2006. Nature Genetics., 38:75-81. [PDF]
The genetic structure of human populations. N.A. Rosenberg, J.K. Pritchard, J.L. Weber, H.M. Cann, K.K. Kidd, L.A. Zhivotovsky and M.W. Feldman, 2002. Science, 298: 2381-2385. [PDF]
Linkage disequilibrium in humans: models and data. J.K. Pritchard and M. Przeworski, 2001. Am. J. Hum. Genet. 69:1-14 [PDF]
Use of unlinked genetic markers to detect population stratification in association studies. JK Pritchard and NA Rosenberg 1999. Am. J. of Hum. Gen. 65: 220-228. [PDF]
Population growth of human Y chromosomes: a study of Y chromosome microsatellites. JK Pritchard, MT Seielstad, A Perez-Lezaun and MW Feldman 1999. Mol. Biol. Evol., 16:1791-1798. [PDF],