Human Genetics

, Volume 131, Issue 4, pp 601–613

Recombination networks as genetic markers in a human variation study of the Old World

  • Asif Javed
  • Marta Melé
  • Marc Pybus
  • Pierre Zalloua
  • Marc Haber
  • David Comas
  • Mihai G. Netea
  • Oleg Balanovsky
  • Elena Balanovska
  • Li Jin
  • Yajun Yang
  • GaneshPrasad ArunKumar
  • Ramasamy Pitchappan
  • Jaume Bertranpetit
  • Francesc Calafell
  • Laxmi Parida
  • The Genographic Consortium
Original Investigation

Abstract

We have analyzed human genetic diversity in 33 Old World populations including 23 populations obtained through Genographic Project studies. A set of 1,536 SNPs in five X chromosome regions were genotyped in 1,288 individuals (mostly males). We use a novel analysis employing subARG network construction with recombining chromosomal segments. Here, a subARG is constructed independently for each of five gene-free regions across the X chromosome, and the results are aggregated across them. For PCA, MDS and ancestry inference with STRUCTURE, the subARG is processed to obtain feature vectors of samples and pairwise distances between samples. The observed population structure, estimated from the five short X chromosomal segments, supports genome-wide frequency-based analyses: African populations show higher genetic diversity, and the general trend of shared variation is seen across the globe from Africa through Middle East, Europe, Central Asia, Southeast Asia, and East Asia in broad patterns. The recombinational analysis was also compared with established methods based on SNPs and haplotypes. For haplotypes, we also employed a fixed-length approach based on information-content optimization. Our recombinational analysis suggested a southern migration route out of Africa, and it also supports a single, rapid human expansion from Africa to East Asia through South Asia.

Supplementary material

439_2011_1104_MOESM1_ESM.doc (581 kb)
Supplemental material 1 (DOC 581 kb)

References

  1. Baird SJ (2006) Phylogenetics: Fisher’s markers of admixture. Heredity 97(2):81–83PubMedCrossRefGoogle Scholar
  2. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265PubMedCrossRefGoogle Scholar
  3. Belle EM, Barbujani G (2007) Worldwide analysis of multiple microsatellites: language diversity has a detectable influence on DNA diversity. Am J Phys Anthropol 133(4):1137–1146PubMedCrossRefGoogle Scholar
  4. Cavalli-Sforza LL, Menozzi P, Piazza A (1994) History and geography of human genes. Princeton University Press, PrincetonGoogle Scholar
  5. Conrad DF, Jakobsson M, Coop G, Wen X, Wall JD, Rosenberg NA, Pritchard JK (2006) A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nat Genet 38(11):1251–1260PubMedCrossRefGoogle Scholar
  6. Delfin F, Salvador JM, Calacal GC, Perdigon HB, Tabbada KA, Villamor LP, Halos SC, Gunnarsdottir E, Myles S, Hughes DA, Xu S, Jin L, Lao O, Kayser M, Hurles ME, Stoneking M, De Ungria MC (2011) The Y-chromosome landscape of the Philippines: extensive heterogeneity and varying genetic affinities of Negrito and non-Negrito groups. Eur J Hum Genet 19(2):224–230PubMedCrossRefGoogle Scholar
  7. Dennell R, Roebroeks W (2005) An Asian perspective on early human dispersal from Africa. Nature 438(7071):1099–1104PubMedCrossRefGoogle Scholar
  8. Durbin RM, Abecasis GR, Altshuler DL, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population-scale sequencing. Nature 467(7319):1061–1073CrossRefGoogle Scholar
  9. Excoffier L, Lischer HEL (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10:564–567PubMedCrossRefGoogle Scholar
  10. Excoffier L, Harding RM, Sokal RR, Pellegrini B, Sanchez-Mazas A (1991) Spatial differentiation of RH and GM haplotype frequencies in Sub-Saharan Africa and its relation to linguistic affinities. Hum Biol 63(3):273–307PubMedGoogle Scholar
  11. Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164(4):1567–1587PubMedGoogle Scholar
  12. Fisher RA (1954) A fuller theory of “Junctions” in inbreeding. Heredity 8:187–197CrossRefGoogle Scholar
  13. Gunnarsdottir ED, Li M, Bauchet M, Finstermeier K, Stoneking M (2011) High-throughput sequencing of complete human mtDNA genomes from the Philippines. Genome Res 21(1):1–11PubMedCrossRefGoogle Scholar
  14. Hammer MF, Woerner AE, Mendez FL, Watkins JC, Cox MP, Wall JD (2010) The ratio of human X chromosome to autosome diversity is positively correlated with genetic distance from genes. Nat Genet 42(10):830–831PubMedCrossRefGoogle Scholar
  15. Henn BM, Gignoux CR, Jobin M, Granka JM, Macpherson JM, Kidd JM, Rodríguez-Botigué L, Ramachandran S, Hon L, Brisbin A, Lin AA, Underhill PA, Comas D, Kidd KK, Norman PJ, Parham P, Bustamante CD, Mountain JL, Feldman MW (2011) Hunter-gatherer genomic diversity suggests a southern African origin for modern humans. Proc Natl Acad Sci USA 108(13):5154–5162PubMedCrossRefGoogle Scholar
  16. Jakobsson M, Rosenberg NA (2007) CLUMPP: a cluster matching and permutation program for dealing with label switching and multimodality in analysis of population structure. Bioinformatics 23(14):1801–1806PubMedCrossRefGoogle Scholar
  17. Jakobsson M, Scholz SW, Scheet P, Gibbs JR, VanLiere JM, Fung HC, Szpiech ZA, Degnan JH, Wang K, Guerreiro R, Bras JM, Schymick JC, Hernandez DG, Traynor BJ, Simon-Sanchez J, Matarin M, Britton A, van de Leemput J, Rafferty I, Bucan M, Cann HM, Hardy JA, Rosenberg NA, Singleton AB (2008) Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451(7181):998–1003PubMedCrossRefGoogle Scholar
  18. Javed A, Pybus M, Mele M, Utro F, Bertranpetit J, Calafell F, Parida L (2011) IRiS: construction of ARG networks at genomic scales. Bioinformatics 27(17):2448–2450PubMedCrossRefGoogle Scholar
  19. Kimura M, Ohta T (1969) The average number of generations until fixation of a mutant gene in a finite population. Genetics 61(3):763–771PubMedGoogle Scholar
  20. Kong A, Thorleifsson G, Gudbjartsson DF, Masson G, Sigurdsson A, Jonasdottir A, Walters GB, Jonasdottir A, Gylfason A, Kristinsson KT, Gudjonsson SA, Frigge ML, Helgason A, Thorsteinsdottir U, Stefansson K (2010) Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467(7319):1099–1103PubMedCrossRefGoogle Scholar
  21. Macaulay V, Hill C, Achilli A, Rengo C, Clarke D, Meehan W, Blackburn J, Semino O, Scozzari R, Cruciani F, Taha A, Shaari NK, Raja JM, Ismail P, Zainuddin Z, Goodwin W, Bulbeck D, Bandelt HJ, Oppenheimer S, Torroni A, Richards M (2005) Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308(5724):1034–1036PubMedCrossRefGoogle Scholar
  22. Mateu E, Calafell F, Lao O, Bonne-Tamir B, Kidd JR, Pakstis A, Kidd KK, Bertranpetit J (2001) Worldwide genetic analysis of the CFTR region. Am J Hum Genet 68(1):103–117PubMedCrossRefGoogle Scholar
  23. Mateu E, Perez-Lezaun A, Martinez-Arias R, Andres A, Valles M, Bertranpetit J, Calafell F (2002) PKLR- GBA region shows almost complete linkage disequilibrium over 70 kb in a set of worldwide populations. Hum Genet 110(6):532–544PubMedCrossRefGoogle Scholar
  24. Melé M, Javed A, Pybus M, Calafell F, Parida L, Bertranpetit J (2010) A new method to reconstruct recombination events at a genomic scale. PLoS Comput Biol 6(11):e1001010PubMedCrossRefGoogle Scholar
  25. Mendizabal I, Valente C, Gusmao A, Alves C, Gomes V, Goios A, Parson W, Calafell F, Alvarez L, Amorim A, Gusmao L, Comas D, Prata MJ (2011) Reconstructing the Indian origin and dispersal of the European Roma: a maternal genetic perspective. PLoS One 6(1):e15988PubMedCrossRefGoogle Scholar
  26. Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, Auton A, Indap A, King KS, Bergmann S, Nelson MR, Stephens M, Bustamante CD (2008) Genes mirror geography within Europe. Nature 456:98–101PubMedCrossRefGoogle Scholar
  27. Parida L, Palamara PF, Javed A (2011) A minimal descriptor of an ancestral recombinations graph. BMC Bioinformatics 12(Suppl 1):S6PubMedCrossRefGoogle Scholar
  28. Patterson N, Price AL, Reich D (2006) Population structure and eigen analysis. PLoS Genet 2(12):e190PubMedCrossRefGoogle Scholar
  29. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155(2):945–959PubMedGoogle Scholar
  30. Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, Zhivotovsky LA, Feldman MW (2002) Genetic structure of human populations. Science 298(5602):2381–2385PubMedCrossRefGoogle Scholar
  31. Schaffner SF, Foo C, Gabriel S, Reich D, Daly MJ, Altshuler D (2005) Calibrating a coalescent simulation of human genome sequence variation. Genome Res 15(11):1576–1583PubMedCrossRefGoogle Scholar
  32. Scheet P, Stephens M (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78(4):629–644PubMedCrossRefGoogle Scholar
  33. Stephens M, Scheet P (2005) Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet 76(3):449–462PubMedCrossRefGoogle Scholar
  34. Tishkoff SA, Dietzch E, Speed W, Pakstis AJ, Kidd JR, Cheung K, Bonné-Tamir B, Santachiara-Benerecetti S, Moral P, Krings M, Pääbo S, Watson E, Risch N, Jenkins T, Kidd KK (1996) Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science 271:1380–1387PubMedCrossRefGoogle Scholar
  35. Tishkoff SA, Goldman A, Calafell F, Speed WC, Deinard AS, Bonne-Tamir B, Kidd JR, Pakstis AJ, Jenkins T, Kidd KK (1998) A global haplotype analysis of the myotonic dystrophy locus: implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations. Am J Hum Genet 62(6):1389–1402PubMedCrossRefGoogle Scholar
  36. Tishkoff SA, Reed FA, Friedlaender FR, Ehret C, Ranciaro A, Froment A, Hirbo JB, Awomoyi AA, Bodo JM, Doumbo O, Ibrahim M, Juma AT, Kotze MJ, Lema G, Moore JH, Mortensen H, Nyambo TB, Omar SA, Powell K, Pretorius GS, Smith MW, Thera MA, Wambebe C, Weber JL, Williams SM (2009) The genetic structure and history of Africans and African Americans. Science 324(5930):1035–1044PubMedCrossRefGoogle Scholar
  37. Wang S, Lewis CM, Jakobsson M, Ramachandran S, Ray N, Bedoya G, Rojas W, Parra MV, Molina JA, Gallo C, Mazzotti G, Poletti G, Hill K, Hurtado AM, Labuda D, Klitz W, Barrantes R, Bortolini MC, Salzano FM, Petzl-Erler ML, Tsuneto LT, Llop E, Rothhammer F, Excoffier L, Feldman MW, Rosenberg NA, Ruiz-Linares A (2007) Genetic variation and population structure in native Americans. PLoS Genet 3(11):e185PubMedCrossRefGoogle Scholar
  38. Watterson GA, Guess HA (1977) Is the most frequent allele the oldest? Theor Popul Biol 11:141–160PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Asif Javed
    • 1
  • Marta Melé
    • 2
  • Marc Pybus
    • 2
  • Pierre Zalloua
    • 3
  • Marc Haber
    • 3
  • David Comas
    • 2
  • Mihai G. Netea
    • 4
  • Oleg Balanovsky
    • 5
    • 6
  • Elena Balanovska
    • 5
  • Li Jin
    • 7
  • Yajun Yang
    • 7
  • GaneshPrasad ArunKumar
    • 8
  • Ramasamy Pitchappan
    • 8
    • 9
  • Jaume Bertranpetit
    • 2
  • Francesc Calafell
    • 2
  • Laxmi Parida
    • 1
  • The Genographic Consortium
  1. 1.Computational Biology CenterIBM T J Watson ResearchYorktownUSA
  2. 2.IBEInstitut de Biologia Evolutiva (CSIC-UPF)BarcelonaSpain
  3. 3.School of MedicineLebanese American UniversityBeirutLebanon
  4. 4.Department of Medicine and Nijmegen Institute for Infection, Inflammation, and ImmunityRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  5. 5.Research Centre for Medical GeneticsMoscowRussia
  6. 6.Vavilov Institute for General GeneticsMoscowRussia
  7. 7.MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical SciencesFudan UniversityShanghaiChina
  8. 8.School of Biological SciencesMadurai Kamaraj UniversityMaduraiIndia
  9. 9.Chettinad Academy of Research and EducationChettinad Health CityChennaiIndia

Personalised recommendations