Ancestral Components of Admixed Genomes in a Mexican Cohort
For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people.
Vyšlo v časopise:
Ancestral Components of Admixed Genomes in a Mexican Cohort. PLoS Genet 7(12): e32767. doi:10.1371/journal.pgen.1002410
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002410
Souhrn
For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people.
Zdroje
1. RosenbergNAPritchardJKWeberJLCannHMKiddKK 2002 Genetic structure of human populations. Science 298 2381 2385
2. LiJZAbsherDMTangHSouthwickAMCastoAM 2008 Worldwide human relationships inferred from genome-wide patterns of variation. Science 319 1100 1104
3. NovembreJJohnsonTBrycKKutalikZBoykoAR 2008 Genes mirror geography within Europe. Nature 456 274
4. WangSLewisCMJakobssonMRamachandranSRayN 2007 Genetic variation and population structure in native Americans. PLoS Genet 3 e185 doi:10.1371/journal.pgen.0030185
5. TishkoffSAReedFAFriedlaenderFREhretCRanciaroA 2009 The genetic structure and history of Africans and African Americans. Science 324 1035 1044
6. SabetiPCReichDEHigginsJMLevineHZRichterDJ 2002 Detecting recent positive selection in the human genome from haplotype structure. Nature 419 832 837
7. WilliamsonSHHubiszMJClarkAGPayseurBABustamanteCD 2007 Localizing recent adaptive evolution in the human genome. PLoS Genet 3 e90 doi:10.1371/journal.pgen.0030090
8. VoightBFKudaravalliSWenXPritchardJK 2006 A map of recent positive selection in the human genome. PLoS Biol 4 e72 doi:10.1371/journal.pbio.0040072
9. PickrellJKCoopGNovembreJKudaravalliSLiJZ 2009 Signals of recent positive selection in a worldwide sample of human populations. Genome Res 19 826 837
10. BonillaCParraEJPfaffCLDiosSMarshallJA 2004 Admixture in the Hispanics of the San Luis Valley, Colorado, and its implications for complex trait gene mapping. Ann Hum Genet 68 139 153
11. PearsonK 1901 On lines and planes of closest fit to systems of points in space. Philosophical Magazine 2 559 572
12. TangHCoramMWangPZhuXRischN 2006 Reconstructing genetic ancestry blocks in admixed individuals. Am J Hum Genet 79 1 12
13. RaikoTIlinAKarhunenJ 2007 Principal Component Analysis for Large Scale Problems with Lots of Missing Values. 691 698 Proceedings of the 18th European conference on Machine Learning. Warsaw, Poland: Springer-Verlag
14. HancockDBRomieuIShiMSienra-MongeJJWuH 2009 Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children. PLoS Genet 5 e1000623 doi:10.1371/journal.pgen.1000623
15. PoolJENielsenR 2009 Inference of historical changes in migration rate from the lengths of migrant tracts. Genetics 181 711 719
16. BighamABauchetMPintoDMaoXAkeyJM 2010 Identifying signatures of natural selection in tibetan and andean populations using dense genome scan data. PLoS Genet 6 e1001116 doi:10.1371/journal.pgen.1001116
17. AndresAMDennisMYKretzschmarWWCannonsJLLee-LinSQ 2010 Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS Genet 6 e1001157 doi:10.1371/journal.pgen.1001157
18. TakayanagiH 2007 Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7 292 304
19. FedelesSVTianXGallagherARMitobeMNishioS 2011 A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet
20. BrycKVelezCKarafetTMoreno-EstradaAReynoldsA 2010 Colloquium paper: genome-wide patterns of population structure and admixture among Hispanic/Latino populations. Proc Natl Acad Sci U S A 107 Suppl 2 8954 8961
21. PriceALPattersonNJPlengeRMWeinblattMEShadickNA 2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909
22. TianCGregersenPKSeldinMF 2008 Accounting for ancestry: population substructure and genome-wide association studies. Hum Mol Genet 17 R143 150
23. Silva-ZolezziIHidalgo-MirandaAEstrada-GilJFernandez-LopezJCUribe-FigueroaL 2009 Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico. Proc Natl Acad Sci U S A 106 8611 8616
24. ZakhariaFBasuAAbsherDAssimesTLGoAS 2009 Characterizing the admixed African ancestry of African Americans. Genome Biol 10 R141
25. SalasACarracedoARichardsMMacaulayV 2005 Charting the ancestry of African Americans. Am J Hum Genet 77 676 680
26. GrossmanSRShylakhterIKarlssonEKByrneEHMoralesS 2010 A composite of multiple signals distinguishes causal variants in regions of positive selection. Science 327 883 886
27. AlbrechtsenAMoltkeINielsenR 2010 Natural selection and the distribution of identity-by-descent in the human genome. Genetics 186 295 308
28. ChoudhrySSeiboldMABorrellLNTangHSerebriskyD 2007 Dissecting complex diseases in complex populations: asthma in latino americans. Proc Am Thorac Soc 4 226 233
29. McEvoyBPLindJMWangETMoyzisRKVisscherPM 2010 Whole-genome genetic diversity in a sample of Australians with deep Aboriginal ancestry. Am J Hum Genet 87 297 305
30. TangHChoudhrySMeiRMorganMRodriguez-CintronW 2007 Recent genetic selection in the ancestral admixture of Puerto Ricans. Am J Hum Genet 81 626 633
31. BrycKAutonANelsonMROksenbergJRHauserSL 2010 Genome-wide patterns of population structure and admixture in West Africans and African Americans. Proc Natl Acad Sci U S A 107 786 791
32. VaethPACaetanoRRamisetty-MiklerSRodriguezLA 2009 Hispanic Americans Baseline Alcohol Survey (HABLAS): alcohol-related problems across Hispanic national groups. J Stud Alcohol Drugs 70 991 999
33. BorrellLNCrawfordNDDalloFJBaqueroMC 2009 Self-reported diabetes in Hispanic subgroup, non-Hispanic black, and non-Hispanic white populations: National Health Interview Survey, 1997–2005. Public Health Rep 124 702 710
34. BrowningBLBrowningSR 2009 A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals. Am J Hum Genet 84 210 223
35. TangHPengJWangPRischNJ 2005 Estimation of individual admixture: analytical and study design considerations. Genet Epidemiol 28 289 301
36. PriceALTandonAPattersonNBarnesKCRafaelsN 2009 Sensitive detection of chromosomal segments of distinct ancestry in admixed populations. PLoS Genet 5 e1000519 doi:10.1371/journal.pgen.1000519
37. FriedmanJHastieTHoflingHTibshiraniR 2007 PATHWISE COORDINATE OPTIMIZATION. The annals of Applied Statistics 1 302 332
38. KongAGudbjartssonDFSainzJJonsdottirGMGudjonssonSA 2002 A high-resolution recombination map of the human genome. Nat Genet 31 241 247
39. QinHMorrisNKangSJLiMTayoB 2010 Interrogating local population structure for fine mapping in genome-wide association studies. Bioinformatics 26 2961 2968
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 12
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