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Partha P Majumder

Publications and source records attributed to Partha P Majumder.

18 recordsLinked to original sources
PubMed2006

Using HapMap data: a cautionary note.

The HapMap data are being widely used in human genetic studies. We show by direct resequencing of a approximately 6-kb region of chromosome 1 that the HapMap data are unreliable for this region. This region contains a recent mitochondrial (mt) DNA insertion. The HapMap data report the corresponding mtDNA variation and not the nuclear DNA variation. In view of mtDNA insertions of varying lengths throughout the human genome and considerable segmental duplications, it is necessary to use the HapMap data cautiously.

Chromosomes, Human, Pair 1↗
PubMed2006

Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene.

AIM: To identify the variants in UDP-glucuronosyltransferase 1 (UGT1A1) gene in Gilbert's syndrome (GS) and to estimate the association between homozygosity for TA insertion and GS in India, as well as the frequency of TA insertion and its impact among normal controls in India. METHODS: Ninety-five GS cases and 95 normal controls were selected. Liver function and other tests were done. The promoter and all 5 exons of UGT1A1 gene were resequenced. Functional assessment of a novel trinucleotide insertion was done by in silico analysis and by estimating UGT1A1 promoter activity carried out by luciferase reporter assay of appropriate constructs in Hep G2 cell line. RESULTS: Among the GS patients, 80% were homozygous for the TA insertion, which was several-fold higher than reports from other ethnic groups. The mean UCB level was elevated among individuals with only one copy of this insertion, which was not significantly different from those with two copies. Many new DNA variants in UGT1A1 gene were discovered, including a trinucleotide (CAT) insertion in the promoter found in a subset (10%) of GS patients, but not among normal controls. In-silico analysis showed marked changes in the DNA-folding of the promoter and functional analysis showed a 20-fold reduction in transcription efficiency of UGT1A1 gene resulting from this insertion, thereby significantly elevating the UCB level. CONCLUSION: The genetic epidemiology of GS is variable across ethnic groups and the epistatic interactions among UGT1A1 promoter variants modulate bilirubin glucuronidation.

Adult↗
PubMed2006

Globally, CYP1B1 mutations in primary congenital glaucoma are strongly structured by geographic and haplotype backgrounds.

PURPOSE: To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide. METHODS: Five intragenic single-nucleotide polymorphisms in CYP1B1-R48G, A119S, V432L, D449D, and N453S-were used to generate haplotype data from 138 Indian patients with PCG and 132 ethnically matched normal controls, which were then analyzed in conjunction with data from other populations. Maximum-likelihood estimates of haplotype frequencies were estimated from the genotype data. Subsets of patients and normal control subjects were also genotyped with respect to eight short tandem repeat (STR) markers around the CYP1B1 locus (D2S305, D2S165, D2S367, D2S2259, D2S391, D2S3337, D2S23678, and D2S286), to gain evolutionary insights. RESULTS: Common mutations in CYP1B1 that are causal of PCG occurred on a uniform haplotype background among Indian patients, which is completely distinct from the modal haplotype background found among unaffected control subjects. Comparison of these data with data from other global regions reveals strong clustering of CYP1B1 mutations by geographic and haplotype backgrounds. The two distinct modal haplotypes found among Indian patients with PCG and control subjects are both ancient with ages of similar magnitudes, as indicated by large variances in the number of repeats at eight STR loci. Together with data from chimpanzee and normal control subjects from India and other global regions, it was possible to make a parsimonious reconstruction of the evolution of these haplotypes. CONCLUSIONS: The strong association of specific haplotypes with some predominant CYP1B1 mutations underlying PCG and the observed geographical clustering, probably due to founder effects, may be useful for predictive testing.

Africa↗
PubMed2006

Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.

OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS: The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS: Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Absorptiometry, Photon↗
PubMed2006

High prevalence of metabolic syndrome and its correlates in two tribal populations of India and the impact of urbanization.

BACKGROUND AND OBJECTIVES: Metabolic syndrome is one of the major causes of morbidity and mortality in the world. The prevalence of this syndrome is high among Asians, including Indians, and is rising, particularly with the adoption of a modernized life style. Whether traditional societies in India have a low prevalence and the extent to which a transition to a modern life style contributes to the increase in prevalence are unknown. To examine the role of environmental and genetic factors in metabolic syndrome we conducted a study in two sub-Himalayan tribal populations with shared ancestry (Toto and Bhutia). The Toto live exclusively in a rural area, whereas a section of the Bhutia has adopted a modern life style. METHODS: Fasting (12 h) blood samples of Toto (n=258); rural Bhutia (n=75) and urban Bhutia (n=230) were collected, with written informed consent. Lipid profile, blood pressures, body fat and other anthropometric parameters were assessed. Criteria suggested by National Cholesterol Education Programme (NCEP) Adult Treatment Panel III (2001) were used for assessment of metabolic syndrome. RESULTS: The prevalence of metabolic syndrome was high (about 30-50%) among the Bhutia, with no significant rural-urban difference. Among the Toto, though the prevalence of metabolic syndrome was low (about 4-9%), their lipid levels were alarmingly adverse (about 37-67% had low HDLcholesterol or high triglyceride levels). There was an additional adverse impact of adoption of urban life-styles (perhaps primarily mediated through dietary changes) on cardiovascular risk factors. INTERPRETATION AND CONCLUSION: Our study suggested that metabolic syndrome and its correlates could be a major health problem even in traditional societies, indicating that this syndrome was not necessarily a result of modernization. Further, our study indicates that genetic factors that adversely affect the levels of such variables have long antiquities in Indian ethnic groups.

Adolescent↗
PubMed2005

Linkage mapping of a complex trait in the New York population of the GAW14 simulated dataset: a multivariate phenotype approach.

Multivariate phenotypes underlie complex traits. Thus, instead of using the end-point trait, it may be statistically more powerful to use a multivariate phenotype correlated to the end-point trait for detecting linkage. In this study, we develop a reverse regression method to analyze linkage of Kofendrerd Personality Disorder affection status in the New York population of the Genetic Analysis Workshop 14 (GAW14) simulated dataset. When we used the multivariate phenotype, we obtained significant evidence of linkage near four of the six putative loci in at least 25% of the replicates. On the other hand, the linkage analysis based on Kofendrerd Personality Disorder status as a phenotype produced significant findings only near two of the loci and in a smaller proportion of replicates.

Chromosome Mapping↗
PubMed2005

Polarity and temporality of high-resolution y-chromosome distributions in India identify both indigenous and exogenous expansions and reveal minor genetic influence of Central Asian pastoralists.

Although considerable cultural impact on social hierarchy and language in South Asia is attributable to the arrival of nomadic Central Asian pastoralists, genetic data (mitochondrial and Y chromosomal) have yielded dramatically conflicting inferences on the genetic origins of tribes and castes of South Asia. We sought to resolve this conflict, using high-resolution data on 69 informative Y-chromosome binary markers and 10 microsatellite markers from a large set of geographically, socially, and linguistically representative ethnic groups of South Asia. We found that the influence of Central Asia on the pre-existing gene pool was minor. The ages of accumulated microsatellite variation in the majority of Indian haplogroups exceed 10,000-15,000 years, which attests to the antiquity of regional differentiation. Therefore, our data do not support models that invoke a pronounced recent genetic input from Central Asia to explain the observed genetic variation in South Asia. R1a1 and R2 haplogroups indicate demographic complexity that is inconsistent with a recent single history. Associated microsatellite analyses of the high-frequency R1a1 haplogroup chromosomes indicate independent recent histories of the Indus Valley and the peninsular Indian region. Our data are also more consistent with a peninsular origin of Dravidian speakers than a source with proximity to the Indus and with significant genetic input resulting from demic diffusion associated with agriculture. Our results underscore the importance of marker ascertainment for distinguishing phylogenetic terminal branches from basal nodes when attributing ancestral composition and temporality to either indigenous or exogenous sources. Our reappraisal indicates that pre-Holocene and Holocene-era--not Indo-European--expansions have shaped the distinctive South Asian Y-chromosome landscape.

Asia, Central↗
PubMed2005

Southward ho!

Explore the source record for details and available documents.

DNA, Mitochondrial↗
PubMed2005

Identification of polymorphic motifs using probabilistic search algorithms.

The problem of identifying motifs comprising nucleotides at a set of polymorphic DNA sites, not necessarily contiguous, arises in many human genetic problems. However, when the sites are not contiguous, no efficient algorithm exists for polymorphic motif identification. A search based on complete enumeration is computationally inefficient. We have developed probabilistic search algorithms to discover motifs of known or unknown lengths. We have developed statistical tests of significance for assessing a motif discovery, and a statistical criterion for simultaneously estimating motif length and discovering it. We have tested these algorithms on various synthetic data sets and have shown that they are very efficient, in the sense that the "true" motifs can be detected in the vast majority of replications and in a small number of iterations. Additionally, we have applied them to some real data sets and have shown that they are able to identify known motifs. In certain applications, it is pertinent to find motifs that contain contrasting nucleotides at the sites included in the motif (e.g., motifs identified in case-control association studies). For this, we have suggested appropriate modifications. Using simulations, we have discovered that the success rate of identification of the correct motif is high in case-control studies except when relative risks are small. Our analyses of evolutionary data sets resulted in the identification of some motifs that appear to have important implications on human evolutionary inference. These algorithms can easily be implemented to discover motifs from multilocus genotype data by simple numerical recoding of genotypes.

Africa↗
PubMed2005

Mapping quantitative trait loci in humans: achievements and limitations.

Recent advances in statistical methods and genomic technologies have ushered in a new era in mapping clinically important quantitative traits. However, many refinements and novel statistical approaches are required to enable greater successes in this mapping. The possible impact of recent findings pertaining to the structure of the human genome on efforts to map quantitative traits is yet unclear.

Genome, Human↗
PubMed2003

Nonrandom distribution of alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22.

The first draft of the human genome has revealed enormous variability in the global distribution of Alu repeat elements. There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. Our analysis of the completely sequenced chromosomes 21 and 22 revealed a striking bias in Alu distribution. These elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins. This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions. The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling. However, in the structural proteins and information genes, these proportions are lower than the other three categories. We suggest that Alu elements might be involved in regulatory mechanisms and are therefore differentially selected in primate genomes.

Alu Elements↗
PubMed2003

Ethnic India: a genomic view, with special reference to peopling and structure.

We report a comprehensive statistical analysis of data on 58 DNA markers (mitochondrial [mt], Y-chromosomal, and autosomal) and sequence data of the mtHVS1 from a large number of ethnically diverse populations of India. Our results provide genomic evidence that (1) there is an underlying unity of female lineages in India, indicating that the initial number of female settlers may have been small; (2) the tribal and the caste populations are highly differentiated; (3) the Austro-Asiatic tribals are the earliest settlers in India, providing support to one anthropological hypothesis while refuting some others; (4) a major wave of humans entered India through the northeast; (5) the Tibeto-Burman tribals share considerable genetic commonalities with the Austro-Asiatic tribals, supporting the hypothesis that they may have shared a common habitat in southern China, but the two groups of tribals can be differentiated on the basis of Y-chromosomal haplotypes; (6) the Dravidian tribals were possibly widespread throughout India before the arrival of the Indo-European-speaking nomads, but retreated to southern India to avoid dominance; (7) formation of populations by fission that resulted in founder and drift effects have left their imprints on the genetic structures of contemporary populations; (8) the upper castes show closer genetic affinities with Central Asian populations, although those of southern India are more distant than those of northern India; (9) historical gene flow into India has contributed to a considerable obliteration of genetic histories of contemporary populations so that there is at present no clear congruence of genetic and geographical or sociocultural affinities.

Chromosomes, Human, Y↗
PubMed2002

Genomic diversities and affinities among four endogamous groups of Punjab (India) based on autosomal and mitochondrial DNA polymorphisms.

Nineteen insertion/deletion and restriction site polymorphisms on autosomal and mitochondrial genomes and mitochondrial DNA hypervariable segment 1 sequences were used to study genetic diversities and affinities among four endogamous groups of Punjab, India. High values of heterozygosity were noted in all four groups, both in the autosomal and mitochondrial genomes. The coefficient of gene differentiation among the groups, however, was found to be low. Genetic distance and phylogenetic analyses based on these data indicated that inferences on affinities among the populations were different when the two sets of loci (autosomal and mitochondrial) were considered separately. We have interpreted these results on the basis of some known historical data on migrations into this region. The results of this study when compared with the findings of some previous studies indicate that there are regional differences in the patterns of correlation between genomic and sociocultural affinities within India.

Alleles↗
PubMedDate not supplied

Prevalence of metabolic syndrome in two tribal populations of the sub-Himalayan region of India: ethnic and rural-urban differences.

This study was undertaken to estimate prevalence of metabolic syndrome in traditional societies in the sub-Himalayan region and to assess the impact of modernization on the risk to the syndrome. Two tribal populations--Toto and Bhutia--with a shared ancestry and habitat were selected. Some Bhutians have adopted a modern lifestyle. The study design permitted assessment of the relative roles of lifestyle and genetic factors in influencing the prevalence of metabolic syndrome. Our study has revealed that metabolic syndrome (or its contributing variables) can be a major health problem, even in traditional rural ethnic groups, indicating that this syndrome is not necessarily a result of modernization or urbanization. Dyslipidemia seems to be the major contributor to metabolic syndrome. Further, our study indicates that genetic factors that adversely affect the levels of such variables have long antiquities in Indian ethnic groups. We find that there is an additional adverse impact of adoption of urban lifestyles (perhaps primarily mediated through dietary changes) on metabolic syndrome.

Adult↗
PubMedDate not supplied

A comparison of two popular statistical methods for estimating the time to most recent common ancestor (TMRCA) from a sample of DNA sequences.

We have compared two statistical methods of estimating the time to most recent common ancestor (TMRCA) from a sample of DNA sequences, which have been proposed by Templeton (1993) and Bandelt et al. (1995). Monte-Carlo simulations were used for generating DNA sequence data. Different evolutionary scenarios were simulated and the estimation procedures were evaluated. We have found that for both methods (i) the estimates are insensitive to demographic parameters and (ii) the standard deviations of the estimates are too high for these methods to be reliably used in practice.

Algorithms↗
PubMedDate not supplied

Mitochondrial DNA variation in ranked caste groups of Maharashtra (India) and its implication on genetic relationships and origins.

BACKGROUND: Polymorphism in mitochondrial DNA have been proven to be useful in studying genetic relationships and origins. The origins of caste populations have remained an enigma and genetic relationships among ranked caste groups are not uniform across geographical regions in India. AIM: This study was undertaken to investigate the nature and extent of mtDNA variation and relationships among caste groups of the western Indian State of Maharashtra and examine the implication of the results on their origins. SUBJECTS AND METHODS: One population was selected from each of the three caste ranks and blood samples were obtained with informed consent from unrelated individuals. The ranked caste populations were: upper (Brahmin; n=31), middle (Maratha; n=41), and lower (Nava Baudh; n=40). Ten relevant restriction site polymorphisms (RSPs) and one Insertion/Deletion (InDel) polymorphism were studied. The Hypervariable Segment 1 (HVS1) was sequenced in a subset of sampled individuals. RESULTS: Four RSP loci were found to be monomorphic in all populations. The InDel locus was monomorphic in two (Brahmin and Maratha) populations. One haplotype, constructed on the basis of the RSPs, was found to be predominant in all populations. Haplotype diversity was of similar magnitudes among Maratha and Nava Baudh (68% and 64%, respectively), and was much higher than among the Brahmin (49%). The frequency of haplogroup M was found to be high in all three groups, but, contrary to expectations, was highest in the upper caste Brahmin. About 10% of Brahmins, however, possessed the haplogroup C. Extensive variation was found in the HVS1 region. The nucleotide diversities and mean number of mismatches were found to be of similar magnitudes in all three groups. CONCLUSIONS: The upper caste group, Brahmin, is genetically distinct from the middle and lower caste groups. However, in view of the highest frequency of haplogroup M among the Brahmin, it appears that there may have been recruitment from other populations into this group.

DNA, Mitochondrial↗