Journal of Genetics

, Volume 87, Issue 1, pp 3–20 | Cite as

Genetic landscape of the people of India: a canvas for disease gene exploration

  • Indian Genome Variation Consortium
Research Article


Analyses of frequency profiles of markers on disease or drug-response related genes in diverse populations are important for the dissection of common diseases. We report the results of analyses of data on 405 SNPs from 75 such genes and a 5.2 Mb chromosome, 22 genomic region in 1871 individuals from diverse 55 endogamous Indian populations. These include 32 large (> 10 million individuals) and 23 isolated populations, representing a large fraction of the people of India. We observe high levels of genetic divergence between groups of populations that cluster largely on the basis of ethnicity and language. Indian populations not only overlap with the diversity of HapMap populations, but also contain population groups that are genetically distinct. These data and results are useful for addressing stratification and study design issues in complex traits especially for heterogeneous populations.


Indian genome variation polymorphism SNP Asia HapMap complex disease pharmacogenomics 


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  1. Abecasis G. R., Ghosh D. and Nichols T. E. 2005 Linkage disequilibrium: ancient history drives the new genetics. Hum. Hered. 59, 118–124.PubMedCrossRefGoogle Scholar
  2. Akey J. M., Zhang G., Zhang K., Jin L. and Shriver M. D. 2002 Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 12, 1805–1814.PubMedCrossRefGoogle Scholar
  3. Bamshad M., Kivisild T., Watkins W. S., Dixon M. E., Ricker C. E., Rao B. B. et al. 2001 Genetic evidence on the origins of Indian caste populations. Genome Res. 11, 994–1004.PubMedCrossRefGoogle Scholar
  4. Basu A., Mukherjee N., Roy S., Sengupta S., Banerjee S., Chakraborty M. et al. 2003 Ethnic India: a genomic view, with special reference to peopling and structure. Genome Res. 13, 2277–2290.PubMedCrossRefGoogle Scholar
  5. Carlson C. S., Eberle M. A., Rieder M. J., Yi Q., Kruglyak L. and Nickerson D. A. 2004 Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am. J. Hum. Genet. 74, 106–120.PubMedCrossRefGoogle Scholar
  6. Cordaux R., Aunger R., Bentley G., Nasidze I., Sirajuddin S. M. and Stoneking M. 2004 Independent origins of Indian caste and tribal paternal lineages. Curr. Biol. 14, 231–235.PubMedGoogle Scholar
  7. Drysdale C. M., McGraw D. W., Stack C. B., Stephens J. C., Judson R. S., Nandabalan K. et al. 2000 Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc. Natl. Acad. Sci. USA 97, 10483–10488.PubMedCrossRefGoogle Scholar
  8. Fogarty M. S., Sinha A. K., and Jaffe A. B. 2006, ATP and the U.S. Innovation System: A Methodology for Identifying Enabling R&D Spillover Networks Gaithersburg, NIST GCR 06-895.Google Scholar
  9. Habib I. 2001 People’s History of India — Part I: Prehistory Aligarh Historians Society and Tulika Books, Aligarh.Google Scholar
  10. Habib I. 2002 People’s History of India Part 2: The Indus Civilization. Aligarh Historians Society and Tulika Books, Aligarh.Google Scholar
  11. Hanna I. H., Dawling S., Roodi N., Guengerich F. P. and Parl F. F. 2000 Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. Cancer Res. 60, 3440–3444.PubMedGoogle Scholar
  12. Heutink P. and Oostra B. A. 2002 Gene finding in genetically isolated populations. Hum. Mol. Genet. 11, 2507–2515.PubMedCrossRefGoogle Scholar
  13. Indian Genome Variation Consortium 2005 The Indian Genome Variation database (IGVdb): a project overview. Hum. Genet. 118, 1–11.CrossRefGoogle Scholar
  14. Israel E., Chinchilli V. M., Ford J. G., Boushey H. A., Cherniack R., Craig T. J. et al. 2004 Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 364, 1505–1512.PubMedCrossRefGoogle Scholar
  15. Kashyap V. K., Guha S., Sitalaximi T., Bindu G. H., Hasnain S. E. and Trivedi R. 2006 Genetic structure of Indian populations based on fifteen autosomal microsatellite loci. BMC Genet. 7, 28.PubMedCrossRefGoogle Scholar
  16. Kelsoe J. R., Spence M. A., Loetscher E., Foguet M., Sadovnick A. D., Remick R. A. et al. 2001 A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22. Proc. Natl. Acad. Sci. USA 98, 585–590.PubMedCrossRefGoogle Scholar
  17. Kivisild T., Rootsi S., Metspalu M., Mastana S., Kaldma K., Parik J. et al. 2003 The genetic heritage of the earliest settlers persists both in Indian tribal and caste populations. Am. J. Hum. Genet. 72, 313–332.PubMedCrossRefGoogle Scholar
  18. Kukreti R., Bhatnagar P., Rao C., Gupta S., Madan B., Das C. et al. 2005 Beta(2)-adrenergic receptor polymorphisms and response to salbutamol among Indian asthmatics. Pharmacogenomics 6, 399–410.PubMedCrossRefGoogle Scholar
  19. Majumder P. P. and Dey B. 2001 Absence of the HIV-1 protective Delta ccr5 allele in most ethnic populations of India. Eur. J. Hum. Genet. 9, 794–796.PubMedCrossRefGoogle Scholar
  20. Nei M. 1977 F-statistics and analysis of gene diversity in subdivided populations. Ann. Hum. Genet. 41, 225–233.PubMedCrossRefGoogle Scholar
  21. Nei M. and Chesser R. K. 1983 Estimation of fixation indices and gene diversities. Ann. Hum. Genet. 41, 253–259.CrossRefGoogle Scholar
  22. Papolos D. F., Faedda G. L., Veit S., Goldberg R., Morrow B., Kucherlapati R. et al. 1996 Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder? Am. J. Psychiatry 153, 1541–1547.PubMedGoogle Scholar
  23. Peltonen L. 2000 Positional cloning of disease genes: advantages of genetic isolates. Hum. Hered. 50, 66–75.PubMedCrossRefGoogle Scholar
  24. Piazza A., Menozzi P. and Cavalli-Sforza L. L. 1980 The HLA-A,B gene frequencies in the world: migration or selection? Hum. Immunol. 1, 297–304.PubMedCrossRefGoogle Scholar
  25. Pritchard J. K., Stephens M. and Donnelly P. 2000 Inference of population structure using multilocus genotype data. Genetics 155, 945–959.PubMedGoogle Scholar
  26. Rao C. R. 1952 p. 390 Advanced Statistical Methods in Biometric Research, John Wiley, New York.Google Scholar
  27. Rosenberg N. A., Mahajan S., Gonzalez-Quevedo C., Blum M. G., Nino-Rosales L., Ninis V. et al. 2006 Low Levels of Genetic Divergence across Geographically and Linguistically Diverse Populations from India. PLoS Genet. 2, 215.CrossRefGoogle Scholar
  28. Roychoudhury S., Roy S., Basu A., Banerjee R., Vishwanathan H., Usha Rani M. V. et al. 2001 Genomic structures and population histories of linguistically distinct tribal groups of India. Hum. Genet. 109, 339–350.PubMedCrossRefGoogle Scholar
  29. Sahoo S., Singh A., Himabindu G., Banerjee J., Sitalaximi T., Gaikwad S. et al. 2006 A prehistory of Indian Y chromosomes: evaluating demic diffusion scenarios. Proc. Natl. Acad. Sci. USA 103, 843–848.PubMedCrossRefGoogle Scholar
  30. Saitou N. and Nei M. 1987 The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406–425.PubMedGoogle Scholar
  31. Schwab S. G. and Wildenauer D. B. 1999 Chromosome 22 workshop report. Am. J. Med. Genet. 88, 276–278.PubMedCrossRefGoogle Scholar
  32. Sengupta S., Zhivotovsky L. A., King R., Mehdi S. Q., Edmonds C. A., Chow C. E. et al. 2006 Polarity and temporality of highresolution Y-chromosome distributions in India identify both indigenous and exogenous expansions and reveal minor genetic influence of central asian pastoralists. Am. J. Hum. Genet. 78, 202–221.PubMedCrossRefGoogle Scholar
  33. Shriver M. D. and Kittles R. A. 2004 Genetic ancestry and the search for personalized genetic histories. Nat. Rev. Genet. 5, 611–618.PubMedCrossRefGoogle Scholar
  34. Singh K. S. 2002 People of India: introduction national series. Oxford University Press, Delhi.Google Scholar
  35. Sinha A. K. 2001 A Fuzzy Measure Theoretic Quantum Approximation of an Abstract System, Case Western Reserve University Cleveland, Ohio.Google Scholar
  36. Sinha A. K., Richoux W. J. and Loparo K. A. 2004 A system-theoretic state description for temporal transitions in electroencephalogram data of severe epileptic patients, 43rd IEEE Conference on Decision and Control, Atlantis, Paradise Island, Bahamas.Google Scholar
  37. Steinbrook R. 2007 HIV in India-a complex epidemic. N. Engl. J Med. 356, 1089–1093.PubMedCrossRefGoogle Scholar
  38. Stephens M., Smith N. J. and Donnelly P. 2001 A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68, 978–989.PubMedCrossRefGoogle Scholar
  39. Thanseem I., Thangaraj K., Chaubey G., Singh V. K., Bhaskar L. V., Reddy B. M., et al. 2006 Genetic affinities among the lower castes and tribal groups of India: inference from Y chromosome and mitochondrial DNA. BMC Genet. 7, 42.PubMedCrossRefGoogle Scholar
  40. Thapar R. 1966 A history of India. Penguin Books, London.Google Scholar
  41. The International HapMap Consortium 2003 The International HapMap Project. Nature 426, 789–796.CrossRefGoogle Scholar
  42. Tishkoff S. A. and Verrelli B. C. 2003 Patterns of human genetic diversity: implications for human evolutionary history and disease. Annu. Rev. Genomics Hum. Genet. 4, 293–340.PubMedCrossRefGoogle Scholar
  43. van den W. E., Wiers R. W., Dessers J., Janssen R. G., Lambrichs E. H., Smeets H. J. et al. 2007 A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers. Alcohol Clin. Exp. Res. 31, 1–10.CrossRefGoogle Scholar
  44. Verma R., Chauhan C., Saleem Q., Gandhi C., Jain S. and Brahmachari S. K. 2004 A nonsense mutation in the synaptogyrin 1 gene in a family with schizophrenia. Biol. Psychiatry 55, 196–199.PubMedCrossRefGoogle Scholar
  45. Verma R., Kubendran S., Das S. K., Jain S. and Brahmachari S. K. 2005 SYNGR1 is associated with schizophrenia and bipolar disorder in southern India. J. Hum. Genet. 50, 635–640.PubMedCrossRefGoogle Scholar
  46. Watkins W. S., Rogers A. R., Ostler C. T., Wooding S., Bamshad M. J., Brassington A. M. et al. 2003 Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms. Genome Res. 13, 1607–1618.PubMedCrossRefGoogle Scholar
  47. Watkins W. S., Prasad B. V., Naidu J. M., Rao B. B., Bhanu B. A., Ramachandran B. et al. 2005 Diversity and divergence among the tribal populations of India. Ann. Hum. Genet. 69, 680–692.PubMedCrossRefGoogle Scholar
  48. Weisberg I., Tran P., Christensen B., Sibani S. and Rozen R. 1998 A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol. Genet. Metab. 64, 169–172.PubMedCrossRefGoogle Scholar
  49. Wright A. F., Carothers A. D. and Pirastu M. 1999 Population choice in mapping genes for complex diseases. Nat. Genet. 23, 397–404.PubMedCrossRefGoogle Scholar

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© Indian Academy of Sciences 2008

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  • Indian Genome Variation Consortium

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