Additional file 3: Table S3. Significantly enriched GO terms in OSCC-GB patients based on 209 gen... more Additional file 3: Table S3. Significantly enriched GO terms in OSCC-GB patients based on 209 genes significantly differentially methylated in their promoter regions and related information.
Several studies have reported association between noninsulin-dependent diabetes mellitus and GC, ... more Several studies have reported association between noninsulin-dependent diabetes mellitus and GC, the vitamin D binding protein of human plasma, with the GC 1 allele in significant excess among diabetics. Additionally, there is a considerable body of animal data suggesting that vitamin D has a significant impact on insulin secretion. Examination of the insulin levels in Dogrib Indians showed that the lowest levels of fasting insulin were associated with the GC IF-IF genotype. The present study examined levels of glucose, C-peptide, and insulin at fasting and 1 hr and 2 hr following a 75 g oral glucose challenge, in a population of Hispanic-Americans and Anglos in the San Luis Valley of southern Colorado. The sample comprised a total of 468 individuals with normal glucose tolerance. Of these, 289 were Anglos and 179 were Hispanic-Americans. An analysis of covariance was performed to determine the effect of the GC genotypes on mean levels of the primary variables--glucose, C-peptide, and insulin--and a secondary variable--insulinogenic index adjusting for the covariates age, body mass index (BMI), gender, and ethnicity. The analyses revealed that there is a significant difference in mean levels of glucose at fasting (F value = 2.46; P = 0.033) among the GC genotypes in the sample. Additionally, the differences in mean levels of 1 hr postprandial glucose among the GC genotypes although not significant at a 5% level, were significant at the 10% level. No other significant phenotypic effects were observed. These analyses are not in concordance with the results of an earlier study, where lower fasting insulin was associated with the GC 1F-1F genotype.
An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered fr... more An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5-fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.
The skin microbiome varies across individuals. The causes of these variations are inadequately un... more The skin microbiome varies across individuals. The causes of these variations are inadequately understood. We tested the hypothesis that inter-individual variation in facial skin microbiome can be significantly explained by variation in sebum and hydration levels in specific facial regions of humans. We measured sebum and hydration from forehead and cheek regions of healthy female volunteers (n = 30). Metagenomic DNA from skin swabs were sequenced for V3-V5 regions of 16S rRNA gene. Altogether, 34 phyla were identified; predominantly Actinobacteria (66.3%), Firmicutes (17.7%), Proteobacteria (13.1%) and Bacteroidetes (1.4%). About 1000 genera were identified; predominantly Propionibacterium (58.6%), Staphylococcus (8.6%), Streptococcus (4.0%), Corynebacterium (3.6%) and Paracoccus (3.3%). A subset (n = 24) of individuals were sampled two months later. Stepwise multiple regression analysis showed that cheek sebum level was the most significant predictor of microbiome composition and ...
The theoretical justifications for using the number of rare alleles observed in a sample and the ... more The theoretical justifications for using the number of rare alleles observed in a sample and the heterozygosity contributed by such alleles to estimate the relative electrophoretic mutation rate (REMR) are given in this note. It is shown that the estimator using the number of alleles has comparatively less bias. While the total heterozygosity contributed by all alleles at a locus has been previously used to estimate REMR with success, an analogous estimator with only rare alleles has large bias over a wide range of effective population size and sample size.
To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary c... more To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide. 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. 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 o...
This study aims to identify (1) a core disruptive behavior disorder (DBD) postulated to presage a... more This study aims to identify (1) a core disruptive behavior disorder (DBD) postulated to presage a substance use disorder, and (2) the relative importance of parental DBD phenotypes, and familial and nonfamilial environmental factors in the determination of DBD in male children. DBD symptom counts and measures of familial and nonfamilial environmentals were collected from intact families ascertained through the presence (SA+) or absence (SA-) of substance dependence in fathers. Multivariate analyses revealed that both behavioral symptoms and environmental measures were significant discriminators of the families. In SA+ families, the child's score DBD was best predicted by magnitudes of parental dyssocial behaviors and by familial environmental factors. However, in SA- families only familial environmental factors were significant predictors of the child's DBD. These findings suggest that in addition to independent actions of familial transmissible and nonfamilial factors, strong genotype-environment interactions may determine DBD in children and that may contribute to the liability for a substance use disorder.
Background: Studies of epigenomic alterations associated with diseases primarily focus on methyla... more Background: Studies of epigenomic alterations associated with diseases primarily focus on methylation profiles of promoter regions of genes, but not of other genomic regions. In our past work (Das et al. 2019) on patients suffering from gingivo-buccal oral cancer – the most prevalent form of cancer among males in India – we have also focused on promoter methylation changes and resultant impact on transcription profiles. Here, we have investigated alterations in non-promoter (gene-body) methylation profiles and have carried out an integrative analysis of gene-body methylation and transcriptomic data of oral cancer patients. Methods: Tumor and adjacent normal tissue samples were collected from 40 patients. Data on methylation in the non-promoter (gene-body) regions of genes and transcriptome profiles were generated and analyzed. Because of high dimensionality and highly correlated nature of these data, we have used Random Forest (RF) and other data-analytical methods.Results: Our inte...
The Human Cell Atlas has been undergoing a massive effort to support global scientific equity. Th... more The Human Cell Atlas has been undergoing a massive effort to support global scientific equity. The co-leaders of its Equity Working Group share some lessons learned in the process.
Background and Objective: Variations in the cytochrome P450, family 1, subfamily B, polypeptide 1... more Background and Objective: Variations in the cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) gene and mutations in the latent transforming growth factor beta binding protein 2 (LTBP2) gene cause autosomal recessive Primary Congenital Glaucoma (PCG). However, in India, only 45% of PCG patients harbor alterations in the CYP1B1 gene. The present study aimed to identify novel genetic variations contributing to unexplained PCG cases in India. Methods: 112 unrelated Indian PCG patients in whom neither chromosome carried a CYP1B1 or an LTBP2 mutation, and 106 matched controls, were recruited for this study. DNA isolated from each case and control was screened for a total of 906,600 single nucleotide polymorphism (SNP) loci using an Affymetrix 6.0 whole genome genotyping array. The marker data were first used for an association analysis followed by multiple test corrections, after an initial adjustment for population stratification. A second approach undertaken in this study was detection of regions...
Additional file 3: Table S3. Significantly enriched GO terms in OSCC-GB patients based on 209 gen... more Additional file 3: Table S3. Significantly enriched GO terms in OSCC-GB patients based on 209 genes significantly differentially methylated in their promoter regions and related information.
Several studies have reported association between noninsulin-dependent diabetes mellitus and GC, ... more Several studies have reported association between noninsulin-dependent diabetes mellitus and GC, the vitamin D binding protein of human plasma, with the GC 1 allele in significant excess among diabetics. Additionally, there is a considerable body of animal data suggesting that vitamin D has a significant impact on insulin secretion. Examination of the insulin levels in Dogrib Indians showed that the lowest levels of fasting insulin were associated with the GC IF-IF genotype. The present study examined levels of glucose, C-peptide, and insulin at fasting and 1 hr and 2 hr following a 75 g oral glucose challenge, in a population of Hispanic-Americans and Anglos in the San Luis Valley of southern Colorado. The sample comprised a total of 468 individuals with normal glucose tolerance. Of these, 289 were Anglos and 179 were Hispanic-Americans. An analysis of covariance was performed to determine the effect of the GC genotypes on mean levels of the primary variables--glucose, C-peptide, and insulin--and a secondary variable--insulinogenic index adjusting for the covariates age, body mass index (BMI), gender, and ethnicity. The analyses revealed that there is a significant difference in mean levels of glucose at fasting (F value = 2.46; P = 0.033) among the GC genotypes in the sample. Additionally, the differences in mean levels of 1 hr postprandial glucose among the GC genotypes although not significant at a 5% level, were significant at the 10% level. No other significant phenotypic effects were observed. These analyses are not in concordance with the results of an earlier study, where lower fasting insulin was associated with the GC 1F-1F genotype.
An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered fr... more An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5-fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.
The skin microbiome varies across individuals. The causes of these variations are inadequately un... more The skin microbiome varies across individuals. The causes of these variations are inadequately understood. We tested the hypothesis that inter-individual variation in facial skin microbiome can be significantly explained by variation in sebum and hydration levels in specific facial regions of humans. We measured sebum and hydration from forehead and cheek regions of healthy female volunteers (n = 30). Metagenomic DNA from skin swabs were sequenced for V3-V5 regions of 16S rRNA gene. Altogether, 34 phyla were identified; predominantly Actinobacteria (66.3%), Firmicutes (17.7%), Proteobacteria (13.1%) and Bacteroidetes (1.4%). About 1000 genera were identified; predominantly Propionibacterium (58.6%), Staphylococcus (8.6%), Streptococcus (4.0%), Corynebacterium (3.6%) and Paracoccus (3.3%). A subset (n = 24) of individuals were sampled two months later. Stepwise multiple regression analysis showed that cheek sebum level was the most significant predictor of microbiome composition and ...
The theoretical justifications for using the number of rare alleles observed in a sample and the ... more The theoretical justifications for using the number of rare alleles observed in a sample and the heterozygosity contributed by such alleles to estimate the relative electrophoretic mutation rate (REMR) are given in this note. It is shown that the estimator using the number of alleles has comparatively less bias. While the total heterozygosity contributed by all alleles at a locus has been previously used to estimate REMR with success, an analogous estimator with only rare alleles has large bias over a wide range of effective population size and sample size.
To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary c... more To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide. 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. 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 o...
This study aims to identify (1) a core disruptive behavior disorder (DBD) postulated to presage a... more This study aims to identify (1) a core disruptive behavior disorder (DBD) postulated to presage a substance use disorder, and (2) the relative importance of parental DBD phenotypes, and familial and nonfamilial environmental factors in the determination of DBD in male children. DBD symptom counts and measures of familial and nonfamilial environmentals were collected from intact families ascertained through the presence (SA+) or absence (SA-) of substance dependence in fathers. Multivariate analyses revealed that both behavioral symptoms and environmental measures were significant discriminators of the families. In SA+ families, the child's score DBD was best predicted by magnitudes of parental dyssocial behaviors and by familial environmental factors. However, in SA- families only familial environmental factors were significant predictors of the child's DBD. These findings suggest that in addition to independent actions of familial transmissible and nonfamilial factors, strong genotype-environment interactions may determine DBD in children and that may contribute to the liability for a substance use disorder.
Background: Studies of epigenomic alterations associated with diseases primarily focus on methyla... more Background: Studies of epigenomic alterations associated with diseases primarily focus on methylation profiles of promoter regions of genes, but not of other genomic regions. In our past work (Das et al. 2019) on patients suffering from gingivo-buccal oral cancer – the most prevalent form of cancer among males in India – we have also focused on promoter methylation changes and resultant impact on transcription profiles. Here, we have investigated alterations in non-promoter (gene-body) methylation profiles and have carried out an integrative analysis of gene-body methylation and transcriptomic data of oral cancer patients. Methods: Tumor and adjacent normal tissue samples were collected from 40 patients. Data on methylation in the non-promoter (gene-body) regions of genes and transcriptome profiles were generated and analyzed. Because of high dimensionality and highly correlated nature of these data, we have used Random Forest (RF) and other data-analytical methods.Results: Our inte...
The Human Cell Atlas has been undergoing a massive effort to support global scientific equity. Th... more The Human Cell Atlas has been undergoing a massive effort to support global scientific equity. The co-leaders of its Equity Working Group share some lessons learned in the process.
Background and Objective: Variations in the cytochrome P450, family 1, subfamily B, polypeptide 1... more Background and Objective: Variations in the cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) gene and mutations in the latent transforming growth factor beta binding protein 2 (LTBP2) gene cause autosomal recessive Primary Congenital Glaucoma (PCG). However, in India, only 45% of PCG patients harbor alterations in the CYP1B1 gene. The present study aimed to identify novel genetic variations contributing to unexplained PCG cases in India. Methods: 112 unrelated Indian PCG patients in whom neither chromosome carried a CYP1B1 or an LTBP2 mutation, and 106 matched controls, were recruited for this study. DNA isolated from each case and control was screened for a total of 906,600 single nucleotide polymorphism (SNP) loci using an Affymetrix 6.0 whole genome genotyping array. The marker data were first used for an association analysis followed by multiple test corrections, after an initial adjustment for population stratification. A second approach undertaken in this study was detection of regions...
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