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Low levels of genetic divergence across geographically and linguistically diverse populations from India.

Rosenberg NA, Mahajan S, Gonzalez-Quevedo C, Blum MG, Nino-Rosales L, Ninis V, Das P, Hegde M, Molinari L, Zapata G, Weber JL, Belmont JW, Patel PI - PLoS Genet. (2006)

Bottom Line: We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry.However, only a relatively small amount of genetic differentiation exists among the Indian populations.Although caution is warranted due to the fact that United States-sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Bioinformatics Program, and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America. rnoah@umich.edu

ABSTRACT
Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in 432 individuals from 15 Indian populations. We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry. However, only a relatively small amount of genetic differentiation exists among the Indian populations. Although caution is warranted due to the fact that United States-sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population.

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Population Structure Inferred from Microsatellite and Insertion/Deletion Polymorphisms(A) Representative estimate of population structure for 1,384 individuals from worldwide populations, including 432 individuals from India. The plot represents the highest-likelihood run among ten STRUCTURE runs with K = 7 clusters. Eight of the other nine runs identified a cluster largely corresponding to India, and five of these eight produced plots nearly identical to the one shown.(B) Representative estimate of population structure for the 432 individuals from India (based on all 1,200 markers). The plot, with K = 4 clusters, represents the highest-likelihood run among all 80 runs performed with K > 1. None of the 80 runs produced clusters that contained the full ancestry of any particular individual. Across these runs, the clusteredness statistic [21], which measures the extent to which a randomly chosen individual has membership in one as opposed to many clusters, ranged from 0.07 to 0.09.
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pgen-0020215-g002: Population Structure Inferred from Microsatellite and Insertion/Deletion Polymorphisms(A) Representative estimate of population structure for 1,384 individuals from worldwide populations, including 432 individuals from India. The plot represents the highest-likelihood run among ten STRUCTURE runs with K = 7 clusters. Eight of the other nine runs identified a cluster largely corresponding to India, and five of these eight produced plots nearly identical to the one shown.(B) Representative estimate of population structure for the 432 individuals from India (based on all 1,200 markers). The plot, with K = 4 clusters, represents the highest-likelihood run among all 80 runs performed with K > 1. None of the 80 runs produced clusters that contained the full ancestry of any particular individual. Across these runs, the clusteredness statistic [21], which measures the extent to which a randomly chosen individual has membership in one as opposed to many clusters, ranged from 0.07 to 0.09.

Mentions: Levels of genetic variation in the Indian populations, as measured by microsatellite heterozygosity, are compatible with a general reduction of this genetic variation statistic with increasing distance from sub-Saharan Africa [20,22], ranging from 0.723 to 0.734 across the Indian groups, compared with ranges of 0.747–0.765 in sub-Saharan Africa, 0.722–0.739 in the Middle East and North Africa, 0.718–0.735 in Europe, 0.683–0.737 in the whole of Asia (with the smallest values in East Asia), and 0.515–0.674 in Oceania and the Americas (Table 1). Analysis of population structure in the full sample of individuals via model-based clustering identifies a genetic cluster (a subgroup with increased similarity of genetic ancestry) corresponding largely to the new samples of Indian descent, together with substantial fractions of the inferred ancestry of previously sampled individuals from Pakistan (Figure 2A). This cluster appears consistently when the data are studied using a model whose number of clusters is seven or more and is sometimes present in analyses using fewer clusters. In analyses with seven clusters (the largest number of clusters for which a single clustering solution was observed in a majority of replicates), the remaining six clusters match those previously observed with a set of 377 loci when the Indian data were not available [19]. A distance-based clustering algorithm produces results that are similar to those of the model-based analysis, with 983 of 1,000 bootstrap replicates supporting a grouping of all Indian populations except Parsis (comparatively recent immigrants to India from Persia around 700–800 CE [23]) and with similarly strong support for other major continental groupings (Figure 3).


Low levels of genetic divergence across geographically and linguistically diverse populations from India.

Rosenberg NA, Mahajan S, Gonzalez-Quevedo C, Blum MG, Nino-Rosales L, Ninis V, Das P, Hegde M, Molinari L, Zapata G, Weber JL, Belmont JW, Patel PI - PLoS Genet. (2006)

Population Structure Inferred from Microsatellite and Insertion/Deletion Polymorphisms(A) Representative estimate of population structure for 1,384 individuals from worldwide populations, including 432 individuals from India. The plot represents the highest-likelihood run among ten STRUCTURE runs with K = 7 clusters. Eight of the other nine runs identified a cluster largely corresponding to India, and five of these eight produced plots nearly identical to the one shown.(B) Representative estimate of population structure for the 432 individuals from India (based on all 1,200 markers). The plot, with K = 4 clusters, represents the highest-likelihood run among all 80 runs performed with K > 1. None of the 80 runs produced clusters that contained the full ancestry of any particular individual. Across these runs, the clusteredness statistic [21], which measures the extent to which a randomly chosen individual has membership in one as opposed to many clusters, ranged from 0.07 to 0.09.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1713257&req=5

pgen-0020215-g002: Population Structure Inferred from Microsatellite and Insertion/Deletion Polymorphisms(A) Representative estimate of population structure for 1,384 individuals from worldwide populations, including 432 individuals from India. The plot represents the highest-likelihood run among ten STRUCTURE runs with K = 7 clusters. Eight of the other nine runs identified a cluster largely corresponding to India, and five of these eight produced plots nearly identical to the one shown.(B) Representative estimate of population structure for the 432 individuals from India (based on all 1,200 markers). The plot, with K = 4 clusters, represents the highest-likelihood run among all 80 runs performed with K > 1. None of the 80 runs produced clusters that contained the full ancestry of any particular individual. Across these runs, the clusteredness statistic [21], which measures the extent to which a randomly chosen individual has membership in one as opposed to many clusters, ranged from 0.07 to 0.09.
Mentions: Levels of genetic variation in the Indian populations, as measured by microsatellite heterozygosity, are compatible with a general reduction of this genetic variation statistic with increasing distance from sub-Saharan Africa [20,22], ranging from 0.723 to 0.734 across the Indian groups, compared with ranges of 0.747–0.765 in sub-Saharan Africa, 0.722–0.739 in the Middle East and North Africa, 0.718–0.735 in Europe, 0.683–0.737 in the whole of Asia (with the smallest values in East Asia), and 0.515–0.674 in Oceania and the Americas (Table 1). Analysis of population structure in the full sample of individuals via model-based clustering identifies a genetic cluster (a subgroup with increased similarity of genetic ancestry) corresponding largely to the new samples of Indian descent, together with substantial fractions of the inferred ancestry of previously sampled individuals from Pakistan (Figure 2A). This cluster appears consistently when the data are studied using a model whose number of clusters is seven or more and is sometimes present in analyses using fewer clusters. In analyses with seven clusters (the largest number of clusters for which a single clustering solution was observed in a majority of replicates), the remaining six clusters match those previously observed with a set of 377 loci when the Indian data were not available [19]. A distance-based clustering algorithm produces results that are similar to those of the model-based analysis, with 983 of 1,000 bootstrap replicates supporting a grouping of all Indian populations except Parsis (comparatively recent immigrants to India from Persia around 700–800 CE [23]) and with similarly strong support for other major continental groupings (Figure 3).

Bottom Line: We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry.However, only a relatively small amount of genetic differentiation exists among the Indian populations.Although caution is warranted due to the fact that United States-sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Bioinformatics Program, and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America. rnoah@umich.edu

ABSTRACT
Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in 432 individuals from 15 Indian populations. We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry. However, only a relatively small amount of genetic differentiation exists among the Indian populations. Although caution is warranted due to the fact that United States-sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population.

Show MeSH
Related in: MedlinePlus