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. 2003 Aug;164(4):1567–1587. doi: 10.1093/genetics/164.4.1567

Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies.

Daniel Falush 1, Matthew Stephens 1, Jonathan K Pritchard 1
PMCID: PMC1462648  PMID: 12930761

Abstract

We describe extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data. Most importantly, we develop methods that allow for linkage between loci. The new model accounts for the correlations between linked loci that arise in admixed populations ("admixture linkage disequilibium"). This modification has several advantages, allowing (1) detection of admixture events farther back into the past, (2) inference of the population of origin of chromosomal regions, and (3) more accurate estimates of statistical uncertainty when linked loci are used. It is also of potential use for admixture mapping. In addition, we describe a new prior model for the allele frequencies within each population, which allows identification of subtle population subdivisions that were not detectable using the existing method. We present results applying the new methods to study admixture in African-Americans, recombination in Helicobacter pylori, and drift in populations of Drosophila melanogaster. The methods are implemented in a program, structure, version 2.0, which is available at http://pritch.bsd.uchicago.edu.

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Selected References

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  1. Agis M., Schlötterer C. Microsatellite variation in natural Drosophila melanogaster populations from New South Wales (Australia) and Tasmania. Mol Ecol. 2001 May;10(5):1197–1205. doi: 10.1046/j.1365-294x.2001.01271.x. [DOI] [PubMed] [Google Scholar]
  2. Anderson E. C., Thompson E. A. A model-based method for identifying species hybrids using multilocus genetic data. Genetics. 2002 Mar;160(3):1217–1229. doi: 10.1093/genetics/160.3.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barton N. H., Hewitt G. M. Adaptation, speciation and hybrid zones. Nature. 1989 Oct 12;341(6242):497–503. doi: 10.1038/341497a0. [DOI] [PubMed] [Google Scholar]
  4. Beaumont M., Barratt E. M., Gottelli D., Kitchener A. C., Daniels M. J., Pritchard J. K., Bruford M. W. Genetic diversity and introgression in the Scottish wildcat. Mol Ecol. 2001 Feb;10(2):319–336. doi: 10.1046/j.1365-294x.2001.01196.x. [DOI] [PubMed] [Google Scholar]
  5. Bertorelle G., Excoffier L. Inferring admixture proportions from molecular data. Mol Biol Evol. 1998 Oct;15(10):1298–1311. doi: 10.1093/oxfordjournals.molbev.a025858. [DOI] [PubMed] [Google Scholar]
  6. Broman K. W., Murray J. C., Sheffield V. C., White R. L., Weber J. L. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet. 1998 Sep;63(3):861–869. doi: 10.1086/302011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chikhi L., Bruford M. W., Beaumont M. A. Estimation of admixture proportions: a likelihood-based approach using Markov chain Monte Carlo. Genetics. 2001 Jul;158(3):1347–1362. doi: 10.1093/genetics/158.3.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper Richard S., Luke Amy, Zhu Xiaofeng, Kan Donghui, Adeyemo Adebowale, Rotimi Charles, Bouzekri Nourdine, Ward Ryk, Rorimi Charles. Genome scan among Nigerians linking blood pressure to chromosomes 2, 3, and 19. Hypertension. 2002 Nov;40(5):629–633. doi: 10.1161/01.hyp.0000035708.02789.39. [DOI] [PubMed] [Google Scholar]
  9. Daly M. J., Rioux J. D., Schaffner S. F., Hudson T. J., Lander E. S. High-resolution haplotype structure in the human genome. Nat Genet. 2001 Oct;29(2):229–232. doi: 10.1038/ng1001-229. [DOI] [PubMed] [Google Scholar]
  10. Dawson K. J., Belkhir K. A Bayesian approach to the identification of panmictic populations and the assignment of individuals. Genet Res. 2001 Aug;78(1):59–77. doi: 10.1017/s001667230100502x. [DOI] [PubMed] [Google Scholar]
  11. Falush Daniel, Wirth Thierry, Linz Bodo, Pritchard Jonathan K., Stephens Matthew, Kidd Mark, Blaser Martin J., Graham David Y., Vacher Sylvie, Perez-Perez Guillermo I. Traces of human migrations in Helicobacter pylori populations. Science. 2003 Mar 7;299(5612):1582–1585. doi: 10.1126/science.1080857. [DOI] [PubMed] [Google Scholar]
  12. Guglielmino C. R., Piazza A., Menozzi P., Cavalli-Sforza L. L. Uralic genes in Europe. Am J Phys Anthropol. 1990 Sep;83(1):57–68. doi: 10.1002/ajpa.1330830107. [DOI] [PubMed] [Google Scholar]
  13. Knowler W. C., Williams R. C., Pettitt D. J., Steinberg A. G. Gm3;5,13,14 and type 2 diabetes mellitus: an association in American Indians with genetic admixture. Am J Hum Genet. 1988 Oct;43(4):520–526. [PMC free article] [PubMed] [Google Scholar]
  14. Kong Augustine, Gudbjartsson Daniel F., Sainz Jesus, Jonsdottir Gudrun M., Gudjonsson Sigurjon A., Richardsson Bjorgvin, Sigurdardottir Sigrun, Barnard John, Hallbeck Bjorn, Masson Gisli. A high-resolution recombination map of the human genome. Nat Genet. 2002 Jun 10;31(3):241–247. doi: 10.1038/ng917. [DOI] [PubMed] [Google Scholar]
  15. Kumar S., Tamura K., Jakobsen I. B., Nei M. MEGA2: molecular evolutionary genetics analysis software. Bioinformatics. 2001 Dec;17(12):1244–1245. doi: 10.1093/bioinformatics/17.12.1244. [DOI] [PubMed] [Google Scholar]
  16. Long J. C. The genetic structure of admixed populations. Genetics. 1991 Feb;127(2):417–428. doi: 10.1093/genetics/127.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McKeigue P. M., Carpenter J. R., Parra E. J., Shriver M. D. Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations. Ann Hum Genet. 2000 Mar;64(Pt 2):171–186. doi: 10.1017/S0003480000008022. [DOI] [PubMed] [Google Scholar]
  18. McKeigue P. M. Mapping genes that underlie ethnic differences in disease risk: methods for detecting linkage in admixed populations, by conditioning on parental admixture. Am J Hum Genet. 1998 Jul;63(1):241–251. doi: 10.1086/301908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nei M., Li W. H. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5269–5273. doi: 10.1073/pnas.76.10.5269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parra E. J., Marcini A., Akey J., Martinson J., Batzer M. A., Cooper R., Forrester T., Allison D. B., Deka R., Ferrell R. E. Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet. 1998 Dec;63(6):1839–1851. doi: 10.1086/302148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pfaff C. L., Parra E. J., Bonilla C., Hiester K., McKeigue P. M., Kamboh M. I., Hutchinson R. G., Ferrell R. E., Boerwinkle E., Shriver M. D. Population structure in admixed populations: effect of admixture dynamics on the pattern of linkage disequilibrium. Am J Hum Genet. 2000 Dec 7;68(1):198–207. doi: 10.1086/316935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rieseberg L. H., Whitton J., Gardner K. Hybrid zones and the genetic architecture of a barrier to gene flow between two sunflower species. Genetics. 1999 Jun;152(2):713–727. doi: 10.1093/genetics/152.2.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rosenberg Noah A., Pritchard Jonathan K., Weber James L., Cann Howard M., Kidd Kenneth K., Zhivotovsky Lev A., Feldman Marcus W. Genetic structure of human populations. Science. 2002 Dec 20;298(5602):2381–2385. doi: 10.1126/science.1078311. [DOI] [PubMed] [Google Scholar]
  24. Satten G. A., Flanders W. D., Yang Q. Accounting for unmeasured population substructure in case-control studies of genetic association using a novel latent-class model. Am J Hum Genet. 2001 Jan 19;68(2):466–477. doi: 10.1086/318195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stephens J. C., Briscoe D., O'Brien S. J. Mapping by admixture linkage disequilibrium in human populations: limits and guidelines. Am J Hum Genet. 1994 Oct;55(4):809–824. [PMC free article] [PubMed] [Google Scholar]
  26. Stephens M., Smith N. J., Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001 Mar 9;68(4):978–989. doi: 10.1086/319501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thiel Bonnie A., Chakravarti Aravinda, Cooper Richard S., Luke Amy, Lewis Sue, Lynn Audrey, Tiwari Hemant, Schork Nicholas J., Weder Alan B. A genome-wide linkage analysis investigating the determinants of blood pressure in whites and African Americans. Am J Hypertens. 2003 Feb;16(2):151–153. doi: 10.1016/s0895-7061(02)03246-6. [DOI] [PubMed] [Google Scholar]
  28. Thompson E. A. The Icelandic admixture problem. Ann Hum Genet. 1973 Jul;37(1):69–80. doi: 10.1111/j.1469-1809.1973.tb01815.x. [DOI] [PubMed] [Google Scholar]
  29. Thornsberry J. M., Goodman M. M., Doebley J., Kresovich S., Nielsen D., Buckler E. S., 4th Dwarf8 polymorphisms associate with variation in flowering time. Nat Genet. 2001 Jul;28(3):286–289. doi: 10.1038/90135. [DOI] [PubMed] [Google Scholar]
  30. Wright A. E. Conditions which govern the Growth of the Bacillus of "Gas Gangrene" in Artificial Culture Media, in the Blood Fluids in vitro, and in the Dead and Living Organism. Proc R Soc Med. 1917;10(GEN):1.1–132. [PMC free article] [PubMed] [Google Scholar]

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