Human Genetics

, Volume 120, Issue 5, pp 713–722 | Cite as

Elevated male European and female African contributions to the genomes of African American individuals

  • Joanne M. Lind
  • Holli B. Hutcheson-Dilks
  • Scott M. Williams
  • Jason H. Moore
  • Myron Essex
  • Eduardo Ruiz-Pesini
  • Douglas C. Wallace
  • Sarah A. Tishkoff
  • Stephen J. O’Brien
  • Michael W. SmithEmail author
Original Investigation


The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis.


Sex-biased gene flow Admixture 



We are grateful to the many individuals whose DNA samples were used in this study. Technical help was provided by Ann Truelove, Guo Kui Pei, and Michael Malasky. Some help with statistical analysis and sample tracking was provided by James Lautenberger and Bailey Kessing, respectively. We appreciate the secretarial assistance of Andrea Smith during the manuscript preparation and publication process, Carolyn Whistler of Scientific Publications, Graphics and Media, SAIC-Frederick who assisted with preparation of the artwork. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Supplementary material

439_2006_261_MOESM1_ESM.doc (70 kb)
Supplementary material


  1. Bedoya G, Montoya P, Garcia J, Soto I, Bourgeois S, Carvajal L, Labuda D, Alvarez V, Ospina J, Hedrick PW, Ruiz-Linares A (2006) Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate. Proc Natl Acad Sci USA 103:7234--7239PubMedCrossRefADSGoogle Scholar
  2. Bolnick DA, Bolnick DI, Smith DG (2006) Asymmetric male and female genetic histories among Native Americans from Eastern North America. Mol Biol Evol (in press)Google Scholar
  3. Briscoe D, Stephens JC, O’Brien SJ (1994) Linkage disequilibrium in admixed populations: applications in gene mapping. J Hered 85:59–63PubMedGoogle Scholar
  4. Carson P, Ziesche S, Johnson G, Cohn JN (1999) Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail 5:178–187PubMedCrossRefGoogle Scholar
  5. Carvajal-Carmona LG, Soto ID, Pineda N, Ortiz-Barrientos D, Duque C, Ospina-Duque J, McCarthy M, Montoya P, Alvarez VM, Bedoya G, Ruiz-Linares A (2000) Strong Amerind/white sex bias and a possible Sephardic contribution among the founders of a population in northwest Colombia. Am J Hum Genet 67:1287–1295PubMedGoogle Scholar
  6. Carvajal-Carmona LG, Ophoff R, Service S, Hartiala J, Molina J, Leon P, Ospina J, Bedoya G, Freimer N, Ruiz-Linares A (2003) Genetic demography of Antioquia (Colombia) and the Central Valley of Costa Rica. Hum Genet 112:534–541PubMedGoogle Scholar
  7. Chakraborty R, Weiss KM (1988) Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci. Proc Natl Acad Sci USA 85:9119–9123PubMedCrossRefADSGoogle Scholar
  8. Chakraborty R, Kamboh MI, Nwankwo M, Ferrell RE (1992) Caucasian genes in American blacks: new data. Am J Hum Genet 50:145–155PubMedGoogle Scholar
  9. Cooper RS, Kaufman JS, Ward R (2003) Race and genomics. N Engl J Med 348:1166–1170PubMedCrossRefGoogle Scholar
  10. Cruciani F, Santolamazza P, Shen P, Macaulay V, Moral P, Olckers A, Modiano D, Holmes S, Destro-Bisol G, Coia V, Wallace DC, Oefner PJ, Torroni A, Cavalli-Sforza LL, Scozzari R, Underhill PA (2002) A back migration from Asia to sub-Saharan Africa is supported by high-resolution analysis of human Y-chromosome haplotypes. Am J Hum Genet 70:1197–1214PubMedCrossRefGoogle Scholar
  11. Da Silva WA Jr, Bortolini MC, Meyer D, Salzano FM, Elion J, Krishnamoorthy R, Schneider MP, De Guerra DC, Layrisse Z, Castellano HM, Weimer TD, Zago MA (1999) Genetic diversity of two African and sixteen South American populations determined on the basis of six hypervariable loci. Am J Phys Anthropol 109:425–437PubMedCrossRefGoogle Scholar
  12. Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data. Linked loci and correlated allele frequencies. Genetics 164:1567–1587PubMedGoogle Scholar
  13. Freedman ML, Haiman CA, Patterson N, McDonald GJ, Tandon A, Waliszewska A, Penney K, Steen RG, Ardlie K, John EM, Oakley-Girvan I, Whittemore AS, Cooney KA, Ingles SA, Altshuler D, Henderson BE, Reich D (2006) Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci USA 103:14068--14073PubMedCrossRefADSGoogle Scholar
  14. Glass B, Li CC (1953) The dynamics of racial intermixture; an analysis based on the American Negro. Am J Hum Genet 5:1–20PubMedGoogle Scholar
  15. Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM (2004) Design and analysis of admixture mapping studies. Am J Hum Genet 74:965–978PubMedCrossRefGoogle Scholar
  16. Ingman M, Gyllensten U (2001) Analysis of the complete human mtDNA genome: methodology and inferences for human evolution. J Hered 92:454–461PubMedCrossRefGoogle Scholar
  17. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30PubMedCrossRefGoogle Scholar
  18. Jobling MA, Tyler-Smith C (2003) The human Y chromosome: an evolutionary marker comes of age. Nat Rev Genet 4:598–612PubMedCrossRefGoogle Scholar
  19. Karafet TM, Osipova LP, Gubina MA, Posukh OL, Zegura SL, Hammer MF (2002) High levels of Y-chromosome differentiation among native Siberian populations and the genetic signature of a boreal hunter-gatherer way of life. Hum Biol 74:761–789PubMedGoogle Scholar
  20. Kayser M, Brauer S, Schadlich H, Prinz M, Batzer MA, Zimmerman PA, Boatin BA, Stoneking M (2003) Y chromosome STR haplotypes and the genetic structure of U.S. populations of African, European, and Hispanic ancestry. Genome Res 13:624–634PubMedCrossRefGoogle Scholar
  21. Knowler WC, Coresh J, Elston RC, Freedman BI, Iyengar SK, Kimmel PL, Olson JM, Plaetke R, Sedor JR, Seldin MF (2005) The family investigation of nephropathy and diabetes (FIND): design and methods. J Diabetes Complicat 19:1–9PubMedCrossRefGoogle Scholar
  22. Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 14:143–149PubMedGoogle Scholar
  23. Long JC, Williams RC, McAuley JE, Medis R, Partel R, Tregellas WM, South SF, Rea AE, McCormick SB, Iwaniec U (1991) Genetic variation in Arizona Mexican Americans: estimation and interpretation of admixture proportions. Am J Phys Anthropol 84:141–157PubMedGoogle Scholar
  24. Maca-Meyer N, Gonzalez AM, Larruga JM, Flores C, Cabrera VM (2001) Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2:13PubMedCrossRefGoogle Scholar
  25. McKeigue PM (1998) 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 63:241–251PubMedCrossRefGoogle Scholar
  26. McLean DC Jr, Spruill I, Gevao S, Morrison EY, Bernard OS, Argyropoulos G, Garvey WT (2003) Three novel mtDNA restriction site polymorphisms allow exploration of population affinities of African Americans. Hum Biol 75:147–161PubMedGoogle Scholar
  27. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC (2003) Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci USA 100:171–176PubMedCrossRefADSGoogle Scholar
  28. Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, Cooper R, Forrester T, Allison DB, Deka R, Ferrell RE, Shriver MD (1998) Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 63:1839–1851PubMedCrossRefGoogle Scholar
  29. Parra EJ, Kittles RA, Argyropoulos G, Pfaff CL, Hiester K, Bonilla C, Sylvester N, Parrish-Gause D, Garvey WT, Jin L, McKeigue PM, Kamboh MI, Ferrell RE, Pollitzer WS, Shriver MD (2001) Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina. Am J Phys Anthropol 114:18–29PubMedCrossRefGoogle Scholar
  30. Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O’Brien SJ, Altshuler D, Daly MJ, Reich D (2004) Methods for high-density admixture mapping of disease genes. Am J Hum Genet 74:979–1000PubMedCrossRefGoogle Scholar
  31. Pfaff CL, Parra EJ, Bonilla C, Hiester K, McKeigue PM, Kamboh MI, Hutchinson RG, Ferrell RE, Boerwinkle E, Shriver MD (2001) Population structure in admixed populations: effect of admixture dynamics on the pattern of linkage disequilibrium. Am J Hum Genet 68:198–207PubMedCrossRefGoogle Scholar
  32. Phimister EG (2003) Medicine and the racial divide. N Engl J Med 348:1081–1082PubMedCrossRefGoogle Scholar
  33. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959PubMedGoogle Scholar
  34. Reich D, Patterson N, Jager PL, McDonald GJ, Waliszewska A, Tandon A, Lincoln RR, Deloa C, Fruhan SA, Cabre P, Bera O, Semana G, Kelly MA, Francis DA, Ardlie K, Khan O, Cree BA, Hauser SL, Oksenberg JR, Hafler DA (2005) A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility. Nat Genet 37:1113–1118PubMedCrossRefGoogle Scholar
  35. Reiner AP, Ziv E, Lind DL, Nievergelt CM, Schork NJ, Cummings SR, Phong A, Burchard EG, Harris TB, Psaty BM, Kwok PY (2005) Population structure, admixture, and aging-related phenotypes in African American adults: the cardiovascular health study. Am J Hum Genet 76:463–477PubMedCrossRefGoogle Scholar
  36. Risch N (1992) Mapping genes for association studies with recently admixed populations. Am J Hum Genet 51(suppl.):13Google Scholar
  37. Semino O, Passarino G, Oefner PJ, Lin AA, Arbuzova S, Beckman LE, De Benedictis G, Francalacci P, Kouvatsi A, Limborska S, Marcikiae M, Mika A, Mika B, Primorac D, Santachiara-Benerecetti AS, Cavalli-Sforza LL, Underhill PA (2000) The genetic legacy of Paleolithic Homo sapiens in extant Europeans: a Y chromosome perspective. Science 290:1155–1159PubMedCrossRefADSGoogle Scholar
  38. Smith MW, O’Brien SJ (2005) Mapping by admixture linkage disequilibrium: advances, limitations and guidelines. Nat Rev Genet 6:623–632PubMedGoogle Scholar
  39. Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O’Brien SJ, Reich D (2004) A high-density admixture map for disease gene discovery in African Americans. Am J Hum Genet 74:1001–1013PubMedCrossRefGoogle Scholar
  40. Stephens JC, Briscoe D, O’Brien SJ (1994) Mapping by admixture linkage disequilibrium in human populations: limits and guidelines. Am J Hum Genet 55:809–824PubMedGoogle Scholar
  41. Tyner J, Houston D (2000) Controlling bodies: the punishment of multi-racialized sexual relations. Antipode 32:387–409CrossRefGoogle Scholar
  42. Underhill PA, Shen P, Lin AA, Jin L, Passarino G, Yang WH, Kauffman E, Bonne-Tamir B, Bertranpetit J, Francalacci P, Ibrahim M, Jenkins T, Kidd JR, Mehdi SQ, Seielstad MT, Wells RS, Piazza A, Davis RW, Feldman MW, Cavalli-Sforza LL, Oefner PJ (2000) Y chromosome sequence variation and the history of human populations. Nat Genet 26:358–361PubMedCrossRefGoogle Scholar
  43. Wallace DC, Brown MD, Lott MT (1999) Mitochondrial DNA variation in human evolution and disease. Gene 238:211–230PubMedCrossRefGoogle Scholar
  44. Wang J (2003) Maximum-likelihood estimation of admixture proportions from genetic data. Genetics 164:747–765PubMedGoogle Scholar
  45. Wells RS, Yuldasheva N, Ruzibakiev R, Underhill PA, Evseeva I, Blue-Smith J, Jin L, Su B, Pitchappan R, Shanmugalakshmi S, Balakrishnan K, Read M, Pearson NM, Zerjal T, Webster MT, Zholoshvili I, Jamarjashvili E, Gambarov S, Nikbin B, Dostiev A, Aknazarov O, Zalloua P, Tsoy I, Kitaev M, Mirrakhimov M, Chariev A, Bodmer WF (2001) The Eurasian heartland: a continental perspective on Y-chromosome diversity. Proc Natl Acad Sci USA 98:10244–10249PubMedCrossRefADSGoogle Scholar
  46. Wen B, Xie X, Gao S, Li H, Shi H, Song X, Qian T, Xiao C, Jin J, Su B, Lu D, Chakraborty R, Jin L (2004) Analyses of genetic structure of tibeto-burman populations reveals sex-biased admixture in southern tibeto-burmans. Am J Hum Genet 74:856–865PubMedCrossRefGoogle Scholar
  47. Xu J, Meyers D, Freije D, Isaacs S, Wiley K, Nusskern D, Ewing C, Wilkens E, Bujnovszky P, Bova GS, Walsh P, Isaacs W, Schleutker J, Matikainen M, Tammela T, Visakorpi T, Kallioniemi OP, Berry R, Schaid D, French A, McDonnell S, Schroeder J, Blute M, Thibodeau S, Trent J et al (1998) Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet 20:175–179PubMedCrossRefGoogle Scholar
  48. Y Chromosome Consortium (2002) A nomenclature system for the tree of human Y-chromosomal binary haplogroups. Genome Res 12:339–348CrossRefGoogle Scholar
  49. Zhu X, Luke A, Cooper RS, Quertermous T, Hanis C, Mosley T, Gu CC, Tang H, Rao DC, Risch N, Weder A (2005) Admixture mapping for hypertension loci with genome-scan markers. Nat Genet 37:177–181PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Joanne M. Lind
    • 1
    • 8
  • Holli B. Hutcheson-Dilks
    • 1
  • Scott M. Williams
    • 2
  • Jason H. Moore
    • 3
  • Myron Essex
    • 4
  • Eduardo Ruiz-Pesini
    • 5
  • Douglas C. Wallace
    • 5
  • Sarah A. Tishkoff
    • 6
  • Stephen J. O’Brien
    • 1
  • Michael W. Smith
    • 1
    • 7
    • 9
    Email author
  1. 1.Laboratory of Genomic Diversity, NCI-Frederick FrederickUSA
  2. 2.Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, and Division of Cardiovascular Medicine, Department of MedicineVanderbilt UniversityNashvilleUSA
  3. 3.Computational Genetics Laboratory, Department of Genetics, Department of Community and Family Medicine, Norris Cotton Cancer CenterDartmouth Medical SchoolLebanonUSA
  4. 4.Harvard AIDS Institute and Department of Immunology and Infectious DiseasesHarvard School of Public HealthCambridgeUSA
  5. 5.Center for Molecular and Mitochondrial Medicine and GeneticsUniversity of CaliforniaIrvineUSA
  6. 6.Department of BiologyUniversity of MarylandCollege ParkUSA
  7. 7.Basic Research ProgramSAIC-Frederick, Inc., NCI-FrederickFrederickUSA
  8. 8.Agnes Ginges Centre for Molecular CardiologyCentenary InstituteSydneyAustralia
  9. 9.National Cancer Institute at Frederick, Bldg 560, Rm 21-74, SAIC-FrederickFrederickUSA

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