Genetic characterisation of the North-West Indian populations: analysis of mitochondrial DNA control region variations.

BACKGROUND: Human mitochondrial DNA presents several interesting characteristics, making it a favourable tool in the field of molecular anthropology, medical genetics, population history, and forensic science. AIM: The present study investigated the mitochondrial DNA (mtDNA) control region variations in diverse ethnic groups of North-West India for which population data is insufficient. SUBJECTS AND METHODS: The complete mtDNA control regions of 197 unrelated (for up to three generations) healthy individuals belonging to different ethnic groups of North-West India were sequenced. The haplotype frequencies, haplogroup distribution, and pairwise FST values between the studied and other worldwide populations were generated to study patterns of variation in human mtDNA. RESULTS: The results ascertained high gene diversity (0.998) in the studied maternal lineages, identifying 166 distinct haplotypes, of which 158 were unique and characterised by 117 variable sites. Three haplogroups: M3, M30, and U7 were observed to be the most prevalent, and phylogeographically a total of 55.86% of sequences were characterised into South Asian, followed by West Eurasian (40.18%) and East Asian (3.96%), ancestry haplogroups. Pairwise genetic differentiation comparisons revealed maternal homogeneity in the studied groups. No population substructure was detected within the North-West Indian populations. CONCLUSION: The results of this preliminary study will contribute to an existing database of mtDNA variations of the Indian population and facilitate prospective studies investigating population genetics and human diseases.

Genetic portrait of North-West Indian population based on X chromosome Alu insertion markers.

In the present study, allele frequencies and forensic parameters of four ethnic groups (Brahmin, Khatri, Jat Sikh, and Scheduled Caste) of Punjab, India, at 10 Alu insertions of X chromosome were calculated. Six Alu markers were observed to be highly polymorphic with no significant deviations from Hardy-Weinberg equilibrium and no linkage disequilibrium present in any marker. Multidimensional plot showed higher genetic affinity of studied populations with Asian populations. Overall, the tested markers were reliable and were found suitable in human forensics and population genetic studies.

Genetic variation and population structure of five ethnic groups from Punjab, North-West India: Analysis of MHC class I polymorphic Alu insertions (POALINs).

Genetic variation and differentiation of five ethnic groups from Punjab, North-West India was characterized by analyzing data on polymorphic Alu insertions (POALINs) within the class I genomic region of major histocompatibility complex (MHC), which is completely non-existent in Indian population. The haplotype frequency, distribution and heterozygosity among these groups and their potential implications in molecular anthropology and evolutionary studies were also determined. A total of 479 unrelated healthy individuals representing five different ethnic groups: Banias, Brahmins, Khatri, Jat Sikhs and Scheduled Castes were genotyped for five MHC Alu elements (AluHG, AluMICB, AluHJ, AluTF and AluHF) using polymerase chain reaction (PCR). All the loci were found to be polymorphic among the studied populations. No significant deviation from Hardy-Weinberg equilibrium was observed, except for the AluHJ locus in Brahmins. The POALINs varied in allele frequency between 0.0260 and 0.4427. The average heterozygosity among the studied groups ranged from 0.1937 in Banias to 0.2666 in Jat Sikhs. The genetic differentiation among the studied groups was observed to be of the order of 0.01302. Single POALIN haplotypes were found to be more frequent than multiple POALIN haplotypes. The results of inter-population differentiations, haplotype frequencies, genetic distances, multidimensional scaling, phylogenetic and structure analyses indicated close genetic relationships between the five ethnic groups of Punjab, North-West India. Analyses of polymorphic Alu loci of MHC genomic region may represent reliable information about the ancestry, demographic history and geographic origins of the various human populations, facilitating better understanding of the evolutionary, forensic and epidemiological prospective.

Correction: Retinoic acid exacerbates chlorpyrifos action in ensuing adipogenic differentiation of C3H10T½ cells in a GSK3ß dependent pathway.

[This corrects the article DOI: 10.1371/journal.pone.0173031.].

Genetic dissection of five ethnic groups from Punjab, North-West India-A study based on Autosomal Markers.

The present study assessed the applicability of Alu insertion elements and Single Nucleotide Polymorphisms (SNPs) in forensic identification and estimated the extent of genetic variation in five major ethnic groups of Punjab, North-West India. A total of 1012 unrelated samples belonging to Banias, Brahmins, Jat Sikhs, Khatris and Scheduled Castes were genotyped for four Alu elements (ACE, APO, PLAT, D1) and six Single Nucleotide Polymorphisms [ESR (PvuII), LPL (PvuII), HTR2A (MspI), DRD2 Taq1A, Taq1B, Taq1D]. Allele frequencies observed heterozygosity and forensic efficacy parameters were determined. The data on the genetic affinity of the studied populations among themselves and with other populations of India was also analysed using a Neighbor-Joining tree and multidimensional scaling plot respectively. All the 10 loci were polymorphic and their average observed heterozygosity ranged from 0.3872 (Banias) to 0.4311 (Scheduled Castes). Allele frequency variation at the 9 out of 10 loci led to statistically significant pairwise differences among the five study population groups. The result from AMOVA, Structure analysis, and Phylogenetic tree suggests that these populations are homogenous. In the multidimensional scaling plot, the present study populations formed a compact cluster clearly separated from other populations, suggesting a unique genetic identity of the Punjab populations as a whole. All these observations suggest that either a recent common origin of these populations or extensive gene flow across the populations that dissolve the original genetic differences. The data generated in this study will be useful for forensic genetics, molecular anthropological and demographic studies.

Retinoic acid exacerbates chlorpyrifos action in ensuing adipogenic differentiation of C3H10T½ cells in a GSK3ß dependent pathway.

The cell differentiation can be exploited as a paradigm to evaluate the effects of noxious chemicals, on human health, either alone or in combinations. In this regard, the effect of a known cell differentiation agent, retinoic acid (RA) was analyzed in the presence of a noxious chemical chlorpyrifos (CPF), an organophosphate (OP), the receptors of which have recently been localized to mesenchymal stem cells (MSCs). The observed imbalance of adipogenic to skeletal differentiation by CPF together with conundrum about adipogenic potential of RA prompted us to delineate their combinatorial effects on C3H10T½MSC-like undifferentiated cells. Based on MTT assay, the cellular viability was retained by CPF at concentrations ranging from 0.01-50µM, beyond which it caused cytotoxicity. These non-toxic concentrations also mildly interfered with adipogenesis of C3H10T½ cells following exposure to adipogenic cocktail. However, upon exposure to RA alone, these MSCs adopted elongated morphology and accumulated lipid vesicles, by day 20, as discerned by phase-contrast and transmission electron microscopy (TEM), in concert with enhanced Oil Red O stained cells. This effect got strongly augmented upon exposure to combination of CPF and RA in a dose-dependent manner. Simultaneous up-regulation in perilipin-1 (PLIN1) and adipsin (ADN) genes, additionally reiterated the adipogenic differentiation. Mechanistically, GSK3ß pathway was found to be a major player, whereby inhibiting it with lithium chloride (LiCl) resulted in complete blockage of lipid accumulation, accompanied by complete down regulation of PLIN1 and ADN gene expression. In conclusion, these observations for the first time, lend evidence that exposure of CPF accompanied by RA directs commitment of C3H10T½ cells to adipogenic differentiation through a process involving a crosstalk at GSK3ß signaling.

Associating genetic variation at Perilipin 1, Complement Factor D and Adiponectin loci to the bone health status in North Indian population.

Osteoporosis, the most common bone metabolic disease affecting nearly 200 million people worldwide is under the strong influence of genetic components. Simultaneously, adipogenesis and osteogenesis are two highly coordinated processes imperative for the maintenance of bone quality and quantity, where any perturbation leads to pathological conditions of obesity, osteopenia and osteoporosis. To delineate this adipogenic-osteogenic connection, a total of 254 cases (T-score<-1.0 SD) and 250 age, gender and ethnicity matched healthy controls (T-score≥-1.0 SD) were recruited from North India after analyzing bone health status employing quantitative ultrasound (QUS) bone densitometer. The genetic variants of Perilipin 1 (PLIN1), Complement Factor D (CFD) and Adiponectin (ADIPOQ) were genotyped using the PCR-RFLP/ARMS-PCR approach. Subjects with CC+CT (PLIN1 rs2304795) and CC+CG (CFD rs1683563) genotypes conferred nearly 1.54-1.87 fold increased risk towards bone deterioration. Predicted RNA secondary structures of rs2304795 corroborated the risk associated with wild type C allele. G allele carriers at the ADIPOQ locus (rs1501299) were more likely to have a lower bone health (1.57-fold). Haplotype analysis revealed the ADIPOQ variants rs1501299 and rs3774261 in slight linkage disequilibrium (LD), nonetheless G/G haplotype was associated with increased risk. 3-locus and 5-locus gene-gene interaction models revealed a greater likelihood of bone deterioration. In conclusion, certain variants of adipogenic genes might serve as potential biomarkers for determining the genetic predisposition towards bone loss in the North Indian population, further, emphasizing the role of impaired metabolism in bone health.

Analysis of ANKKI (rs1800497) and DRD2 (rs1079597, rs1800498) variants in five ethnic groups from Punjab, North-West India.

Dopamine D2 receptor (DRD2) is one of the essential neurotransmitters in the brain studied extensively in the field of psychiatric disorders, alcoholic behaviors and Pharmacology. It is also a promising gene for studying the evolutionary and genetic variation among populations. The present study was an attempt to understand the extent of genetic variation among five different ethnic groups (Bania, Brahmin, Jat Sikh, Khatri and Scheduled caste) of Punjab (North West India). A total of 1012 individuals belonging to the above mentioned groups were analyzed for three TaqI Polymorphic loci of DRD2 and ankyrin repeat and kinase domain containing 1 (ANKKI) using the allele frequencies and haplotype frequency distribution pattern. All the three loci were found to be polymorphic among the studied populations. The average heterozygosity for all loci in these ethnic groups was fairly substantial ranging from 0.3936 to 0.4986. The genetic differentiation among the population was observed to be in order of 0.0053.Among of the eight studied haplotypes, only six were shared by all the ethnic groups. TaqID and TaqIB loci were reported to be in significantly higher linkage disequilibrium (LD) in Scheduled Caste only, whereas TaqIA and TaqID showed modest LD in Brahmin, Jat Sikh and Khatri. Multidimensional scaling analysis revealed that the studied ethnic groups formed a close cluster, suggesting similar genetic structure of these populations which are in close proximity with other Indo European speaking North Indian and western Indian population groups. Overall this study highlights the genomic uniformity among the ethnic groups of Punjab (North-West India) owing to their common ancestral history and geographical closeness.