My research group uses computational approaches to answer questions regarding the evolutionary processes that have shaped human genetic diversity and disease. The questions that drive our research are: What explains the frequency spectrum of human genetic diversity and its variation across functional categories of sites? How is human genetic diversity distributed across global and local scales? What can the spatial distribution of variation reveal about past human migrations/dispersal and selective processes? How can we best make individual-based predictions of genetic risk and ancestry? How can we use evolutionary insights to improve the genetic mapping of disease traits?
To address these questions, we develop and test computational methods for population genetic analysis and apply these methods to large-scale data. In our work, we rely on an interdisciplinary skill set that draws from computation, statistics, genetics, human history, and anthropology. Examples of our results include analyses of high-throughput genotyping array and sequencing data to reveal the spatial structure of variation in Europe; analyses of large-scale sequencing data to describe the abundance and distribution of rare variants in humans; and development of methods for generation recombination maps from admixed individuals.
The group also has an aim to translate advances in human population genetics to non-model organisms. In this arena, we have helped advance studies of dog domestication and wolf population history, developed methods to empower studies of bird migration by way of combining genetic and isotopic methods for spatial assignment, and developed methods to extract more subtle information from pooled sequences and metagenomic data.
Analysis of rare variant population structure in Europeans explains differential stratification of gene-based tests.
(2014 Sep) Eur J Hum Genet
. 2014 Sep;22(9):1137-44. doi: 10.1038/ejhg.2013.297. Epub 2014 Jan 8. 24398795
Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European.
(2014 Mar) Nature
. 2014 Mar 13;507(7491):225-8. doi: 10.1038/nature12960. Epub 2014 Jan 26. 24463515
Characterizing bias in population genetic inferences from low-coverage sequencing data.
(2014 Mar) Mol Biol Evol
. 2014 Mar;31(3):723-35. doi: 10.1093/molbev/mst229. Epub 2013 Nov 27. 24288159
forqs: forward-in-time simulation of recombination, quantitative traits and selection.
(2014 Feb) Bioinformatics
. 2014 Feb 15;30(4):576-7. doi: 10.1093/bioinformatics/btt712. Epub 2013 Dec 10. 24336146
Genome sequencing highlights the dynamic early history of dogs.
(2014 Jan) PLoS Genet
. 2014 Jan;10(1):e1004016. doi: 10.1371/journal.pgen.1004016. Epub 2014 Jan 16. 24453982
Novel statistical methods for integrating genetic and stable isotope data to infer individual-level migratory connectivity.
(2013 Aug) Mol Ecol
. 2013 Aug;22(16):4163-76. doi: 10.1111/mec.12393. Epub 2013 Jul 30. 23906339
Maximum likelihood estimation of frequencies of known haplotypes from pooled sequence data.
(2013 May) Mol Biol Evol
. 2013 May;30(5):1145-58. doi: 10.1093/molbev/mst016. Epub 2013 Jan 30. 23364324
An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people.
(2012 Jul) Science
. 2012 Jul 6;337(6090):100-4. doi: 10.1126/science.1217876. Epub 2012 May 17. 22604722
A model-based approach for analysis of spatial structure in genetic data.
(2012 Jun) Nat Genet
. 2012 May 20;44(6):725-31. doi: 10.1038/ng.2285. 22610118
Human population structure and the adaptive response to pathogen-induced selection pressures.
(2012 Mar) Philos Trans R Soc Lond B Biol Sci
. 2012 Mar 19;367(1590):878-86. doi: 10.1098/rstb.2011.0305. 22312055
Perspectives on human population structure at the cusp of the sequencing era.
(2011) Annu Rev Genomics Hum Genet
. 2011;12:245-74. doi: 10.1146/annurev-genom-090810-183123. 21801023
Recombination rates in admixed individuals identified by ancestry-based inference.
(2011 Sep) Nat Genet
. 2011 Jul 20;43(9):847-53. doi: 10.1038/ng.894. 21775992
Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication.
(2010 Apr) Nature
. 2010 Apr 8;464(7290):898-902. doi: 10.1038/nature08837. Epub 2010 Mar 17. 20237475
Spatial patterns of variation due to natural selection in humans.
(2009 Nov) Nat Rev Genet
. 2009 Nov;10(11):745-55. doi: 10.1038/nrg2632. Epub 2009 Oct 13. 19823195
Likelihood-based inference in isolation-by-distance models using the spatial distribution of low-frequency alleles.
(2009 Nov) Evolution
. 2009 Nov;63(11):2914-25. doi: 10.1111/j.1558-5646.2009.00775.x. Epub 2009 Jul 16. 19624728
Fast model-based estimation of ancestry in unrelated individuals.
(2009 Sep) Genome Res
. 2009 Sep;19(9):1655-64. doi: 10.1101/gr.094052.109. Epub 2009 Jul 31. 19648217
Genes mirror geography within Europe.
(2008 Nov) Nature
. 2008 Nov 6;456(7218):98-101. doi: 10.1038/nature07331. Epub 2008 Aug 31. 18758442
Interpreting principal component analyses of spatial population genetic variation.
(2008 May) Nat Genet
. 2008 May;40(5):646-9. doi: 10.1038/ng.139. Epub 2008 Apr 20. 18425127
The geographic spread of the CCR5 Delta32 HIV-resistance allele.
Accounting for background nucleotide composition when measuring codon usage bias.
(2002 Aug) Mol Biol Evol
. 2002 Aug;19(8):1390-4. 12140252