DNA Sequence Variation and Haplotype Structure of the ICAM1 and TNF Genes in 12 Ethnic Groups of India Reveal Patterns of Importance in Designing Association Studies

Sengupta, Sanghamitra; Farheen, Shabana; Mukherjee, Neelanjana; Dey, Badal; Mukhopadhyay, Barun; Sil, Samir Kumar; Prabhakaran, N.; Ramesh, A.; Edwin, Deepa; Rani, Monika; Mitra, Mitashree; Mahadik, Chitra Thakur; Singh, Sarva Jit; Sehgal, S. C.; Majumder, Partha P.

doi:10.1046/j.1529-8817.2003.00126.x

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…The genetic diversity within South Asian populations potentially introduces significant confounding in an association study because of population structure. 45 To control for spurious associations due to systematic differences in ancestry between the L and H groups, we composed the two DNA pools to be used in the pooled genotyping with individuals who were matched for ancestry. The genetic ancestry of the 395 L and 383 H individuals was investigated by individually genotyping them for a set of 312 unlinked GC SNPs.…”

Section: Population Structure and Construction Of Balanced Poolsmentioning

confidence: 99%

A Genomewide Association Study of Skin Pigmentation in a South Asian Population

Stokowski

Pant

Dadd

et al. 2007

The American Journal of Human Genetics

262

241

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We have conducted a multistage genomewide association study, using 1,620,742 single-nucleotide polymorphisms to systematically investigate the genetic factors influencing intrinsic skin pigmentation in a population of South Asian descent. Polymorphisms in three genes--SLC24A5, TYR, and SLC45A2--yielded highly significant replicated associations with skin-reflectance measurements, an indirect measure of melanin content in the skin. The associations detected in these three genes, in an additive manner, collectively account for a large fraction of the natural variation of skin pigmentation in a South Asian population. Our study is the first to interrogate polymorphisms across the genome, to find genetic determinants of the natural variation of skin pigmentation within a human population.

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Section: Population Structure and Construction Of Balanced Poolsmentioning

confidence: 99%

A Genomewide Association Study of Skin Pigmentation in a South Asian Population

Stokowski

Pant

Dadd

et al. 2007

The American Journal of Human Genetics

262

241

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“…These have been reported in Sengupta et al (2004) and are summarized in table 1. Tribal groups possess 22 of these 29 sites, while caste groups possess 21.…”

Section: Resultsmentioning

confidence: 99%

Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection

Sengupta

Farheen

Mukherjee

et al. 2007

J Genet

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We have studied DNA sequence variation in and around the genes ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India, with a view to investigating the relative roles of demographic history and natural selection in shaping the observed patterns of variation. The total numbers of single nucleotide polymorphisms (SNPs) detected at the ICAM1 and TNF loci were 29 and 12, respectively. Haplotype and allele frequencies differed significantly across populations. The site frequency spectra at these loci were significantly different from those expected under neutrality, and showed an excess of intermediate-frequency variants consistent with balancing selection. However, as expected under balancing selection, there was no significant reduction of F S T values compared to neutral autosomal loci. Mismatch distributions were consistent with population expansion for both loci. On the other hand, the phylogenetic network among haplotypes for the TNF locus was similar to expectations under population expansion, while that for the ICAM1 was as expected under balancing selection. Nucleotide diversity at the ICAM1 locus was an order of magnitude lower in the promoter region, compared to the introns or exons, but no such difference was noted for the TNF gene. Thus, we conclude that the pattern of nucleotide variation in these genes has been modulated by both demographic history and selection. This is not surprising in view of the known allelic associations of several polymorphisms in these genes with various diseases, both infectious and noninfectious.[Sengupta S., Farheen S., Mukherjee N. and Majumder P. P. 2007 Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection. J. Genet. 86,[225][226][227][228][229][230][231][232][233][234][235][236][237][238][239]

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“…However, between subpopulations, the extent of haplotype diversity is highly variable. Therefore, genomic diversity of the Indian ethnic groups coupled with an underlying genomic unity also provides an opportunity to replicate findings in groups of genetically similar populations (Sengupta et al 2004).…”

Section: Introductionmentioning

confidence: 99%

“…The Indian subpopulations' wide diversity shows extensive variations in frequencies of alleles and haplotypes of common polymorphisms (Bhattacharyya et al 1999;Roy et al , 2003Chandak et al 2002;Nagarkatti et al 2004aNagarkatti et al , 2004bPasha et al 2002; as well as occurrence of some private polymorphisms and mutations (Pramanik et al 2000;Mahajan et al 2004, Sengupta et al 2004. Several studies on Indian subpopulations have revealed founders for disease mutations and helped in understanding the origins of monogenic diseases in India (Saleem et al 2000(Saleem et al , 2002(Saleem et al , 2003Mittal et al 2005;Bahl et al 2005).…”

Section: Introductionmentioning

confidence: 99%

“…These findings suggest the significance of population stratification in designing case-control association studies. Case-control studies carried out in the Indian population sometimes reveal observations distinct from other world populations (Ramana et al 2000;Kukreti et al 2002;Thangaraj et al 2002;Sengupta et al 2004;Rajput et al 2005). Using SNPs and repeat polymorphisms, both novel and reported, studies have been successful in identifying at-risk markers or haplotypes for particular diseases (Choudhry et al 2001;Ahsan et al 2004;Nagarkatti et al 2004aNagarkatti et al , 2004bVerma et al 2004;Verma et al (in press)).…”

Section: Introductionmentioning

confidence: 99%

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The Indian Genome Variation database (IGVdb): a project overview

2005

Hum Genet

128

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Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning languages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacogenomics, one needs to understand the diversity and relatedness at the genetic level in such a diverse population. In this backdrop, six constituent laboratories of the Council of Scientific and Industrial Research (CSIR), with funding from the Government of India, initiated a network program on predictive medicine using repeats and single nucleotide polymorphisms. The Indian Genome Variation (IGV) consortium aims to provide data on validated SNPs and repeats, both novel and reported, along with gene duplications, in over a thousand genes, in 15,000 individuals drawn from Indian subpopulations. These genes have been selected on the basis of their relevance as functional and positional candidates in many common diseases including genes relevant to pharmacogenomics. This is the first large-scale comprehensive study of the structure of the Indian population with wide-reaching implications. A comprehensive platform for Indian Genome Variation (IGV) data management, analysis and creation of IGVdb portal has also been developed. The samples are being collected following ethical guidelines of Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), India. This paper reveals the structure of the IGV project highlighting its various aspects like genesis, objectives, strategies for selection of genes, identification of the Indian subpopulations, collection of samples and discovery and validation of genetic markers, data analysis and monitoring as well as the project's data release policy.

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DNA Sequence Variation and Haplotype Structure of the ICAM1 and TNF Genes in 12 Ethnic Groups of India Reveal Patterns of Importance in Designing Association Studies

Cited by 15 publications

References 16 publications

A Genomewide Association Study of Skin Pigmentation in a South Asian Population

A Genomewide Association Study of Skin Pigmentation in a South Asian Population

Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection

The Indian Genome Variation database (IGVdb): a project overview

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