A linguistically informed autosomal STR survey of human populations residing in the greater Himalayan region.

The greater Himalayan region demarcates two of the most prominent linguistic phyla in Asia: Tibeto-Burman and Indo-European. Previous genetic surveys, mainly using Y-chromosome polymorphisms and/or mitochondrial DNA polymorphisms suggested a substantially reduced geneflow between populations belonging to these two phyla. These studies, however, have mainly focussed on populations residing far to the north and/or south of this mountain range, and have not been able to study geneflow patterns within the greater Himalayan region itself. We now report a detailed, linguistically informed, genetic survey of Tibeto-Burman and Indo-European speakers from the Himalayan countries Nepal and Bhutan based on autosomal microsatellite markers and compare these populations with surrounding regions. The genetic differentiation between populations within the Himalayas seems to be much higher than between populations in the neighbouring countries. We also observe a remarkable genetic differentiation between the Tibeto-Burman speaking populations on the one hand and Indo-European speaking populations on the other, suggesting that language and geography have played an equally large role in defining the genetic composition of present-day populations within the Himalayas.

SLC11A1 and VDR gene variants and susceptibility to tuberculosis and disease progression in East India.

SETTING: Despite efforts at disease control, the incidence of tuberculosis (TB) remains high in India. OBJECTIVE: To assess the role of VDR and SLC11A1 gene polymorphisms in the development of pulmonary TB (PTB) in an ethnically matched population of India. DESIGN: In this case-control study, five variants (INT4/ rs3731865, 823C/T/rs17221959, D543N/rs17235409, 577G/A/rs1059823 and TGTG deletion-3UTR/rs172 35416) of SLC11A1 and three (BsmI/rs1544410, FokI/ rs10735810 and TaqI/rs731236) of the VDR gene were studied in 101 TB patients and 225 controls from Kolkata, India. RESULTS: Statistically significant associations were ob- served for INT4: GC (OR 4.54 95%CI 2.38-8.68), CC (OR 35.20, 95%CI 9.15-135.38), 3 UTR (TGTG+ /-, OR 2.96, 95%CI 1.52-5.78), TGTG- /- (OR 3.52, 95%CI 1.62-7.61) and 823C/T (CT, OR 0.31, 95%CI 0.17-0.58) variants of the SLC11A1 gene. Significantly different genotype frequencies between different groups of patients elucidated the role of the INT4 (P = 0.031), 577G/A (P = 0.033) and FokI (P = 0.02) variants in disease progression and the development of cavitary disease. Five haplotypes were also identified as having a significant association with PTB. CONCLUSION: This study, the first to include evidence on 577G/A and INT4, reports a significant association between SLC11A1 gene variants and PTB with respect to susceptibility and subsequent disease progression in East India.

Allele frequencies of 20 Y-chromosomal short tandem repeat loci in a tribal population of Deccan Plateau, India.

POPULATION: Eighty male individuals from a nomadic tribal population belonging to Dravidian and Indo-Caucasian ethnicities from Deccan Plateau, Andhra Pradesh, India, were analyzed in the present study.

Allele frequency distribution at 15 autosomal STR loci in Panggi, Komkar and Padam sub tribes of Adi, a Tibeto-Burman speaking population of Arunachal Pradesh, India.

Fifteen autosomal STR loci were analyzed in 223 healthy individuals belonging to three remote, isolated Tibeto-Burman speaking sub tribes namely, Panggi, Komkar and Padam of Adi tribe of Arunachal Pradesh, India. The analyzed markers exhibited a high degree of polymorphism in the studied populations. Statistical parameters of forensic interest; observed heterozygosity, probability of homozygosity, exact test, likelihood ratio test, power of discrimination, power of exclusion, match probability and typical paternity index were determined for all loci. The average heterozygosity values were found to be low in the three populations (Panggi: 0.7747; Komkar: 0.7742 and Padam: 0.7663). The combined power of discrimination and power of exclusion were 0.9999 in the studied populations thereby revealing the high forensic significance of the chosen markers. The study indicates the utility of the tested microsatellite markers in forensic human identification, paternity testing and human population genetic studies.

Molecular phylogeny of musk deer: a genomic view with mitochondrial 16S rRNA and cytochrome b gene.

The phylogenetic status of the infra order Pecora is controversial, even though it is supported by paleontological, morphological, and molecular evidence. We analyzed two mitochondrial genes (i.e., 16S rRNA and cytochrome b) to resolve the phylogenetic position of pecoran species, i.e., the Bovidae, Cervidae, and Moschidae endemic to the Indian subcontinent. We used phylogenetic analysis based on different algorithms, including neighbor joining, maximum parsimony, Bayesian inference, maximum likelihood, minimum evolution, median joining network, along with multidimensional scaling, and DNA word analysis. Our results established the basal position of Tragulidae and the monophyly of the infra order Pecora within the Suborder Ruminantia. Our results also demonstrated that Bovidae, Cervidae, and Moschidae are allied with the placement of musk deer as more closely related to bovids than to cervids. Molecular dating based on sequence analysis shows that the radiation of Pecora occurred during the early Oligocene and that the majority of the pecoran families radiated and dispersed rapidly during the Oligocene/Miocene transition.

Allele frequency distribution based on 17 STR markers in three major Dravidian linguistic populations of Andhra Pradesh, India.

Allele frequencies for 15 tetranucleotides and 2 pentanucleotides repeat loci were determined in 317 unrelated, healthy individuals of Andhra Pradesh, India, belonging to three pre-dominant endogamous populations namely, Kappu Naidu, Kamma Chaudhary and Kapu Reddy. Adherence to the expectations of the Hardy-Weinberg equilibrium (HWE) was confirmed for all loci with few exceptions, which were not significant after applying Bonferroni's correction. Statistical parameters of forensic interest; observed heterozygosity, probability of homozygosity, probability of extact test, power of discrimination, match probability, polymorphism information content, power of exclusion and mean paternity index were determined for all loci. The present study reveals that Penta E and D2S1338 are the most informative loci in all the studied populations. The combined power of discrimination was greater than 0.976, whereas the cumulative power of exclusion gave an expected value of 0.9999 for all the tested microsatellite loci. No difference was observed in the discriminatory power of 15 loci in studied populations on comparison with other populations of India. Population differentiation tests revealed significant differences between the studied and neighboring populations at several loci. Analyzed parameters indicate the utility and efficacy of the studied 17 STR systems as a powerful tool in forensic human identification, paternity testing and human population genetic studies.

Genomic variation in the mitochondrially encoded cytochrome b (MT-CYB) and 16S rRNA (MT-RNR2) genes: characterization of eight endangered Pecoran species.

In an effort to develop species-specific identification markers, we examined genetic variants and molecular signatures within genes encoding mitochondrial cytochrome b and 16S rRNA in eight endangered Pecoran species endemic to the Indian peninsula. Our results revealed that the cytochrome b gene exhibited higher sequence diversity than the 16S rRNA gene, both between and within species. However, the 16S rRNA gene harboured a larger number of species-specific mutation sites compared with the cytochrome b gene, suggesting that it could be useful for species identification. Indeed, we successfully used 'forensically informative nucleotide sequencing' (FINS) analysis of the 16S rRNA gene to identify two previously unknown biological specimens.

Genetic structure of Indian populations based on fifteen autosomal microsatellite loci.

BACKGROUND: Indian populations endowed with unparalleled genetic complexity have received a great deal of attention from scientists world over. However, the fundamental question over their ancestry, whether they are all genetically similar or do exhibit differences attributable to ethnicity, language, geography or socio-cultural affiliation is still unresolved. In order to decipher their underlying genetic structure, we undertook a study on 3522 individuals belonging to 54 endogamous Indian populations representing all major ethnic, linguistic and geographic groups and assessed the genetic variation using autosomal microsatellite markers. RESULTS: The distribution of the most frequent allele was uniform across populations, revealing an underlying genetic similarity. Patterns of allele distribution suggestive of ethnic or geographic propinquity were discernible only in a few of the populations and was not applicable to the entire dataset while a number of the populations exhibited distinct identities evident from the occurrence of unique alleles in them. Genetic substructuring was detected among populations originating from northeastern and southern India reflective of their migrational histories and genetic isolation respectively. CONCLUSION: Our analyses based on autosomal microsatellite markers detected no evidence of general clustering of population groups based on ethnic, linguistic, geographic or socio-cultural affiliations. The existence of substructuring in populations from northeastern and southern India has notable implications for population genetic studies and forensic databases where broad grouping of populations based on such affiliations are frequently employed.

Polymorphisms at fifteen tetrameric short tandem repeat loci in three ethnic populations of Bengal, India.

The study presents allele frequency data at 15 tetrameric short tandem repeat (STR) loci (D3S1358, THO1, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, CSF1PO, vWA, D8S1179, TPOX, D2S1338, D19S433 and FGA) in three ethnic populations--Mahishya, Bauri and Namasudra of Bengal to evaluate their utility in Forensic testing and understanding population structure and dynamics. A total of 169 individuals were studied from the selected populations. On an average the combined power of discrimination and power of exclusion in these groups was found 0.97 and 0.99, respectively. The allele distribution pattern shows possible genetic admixture between these ethnic groups which could be attributed to their close geographical proximity and occupying almost similar position in the social hierarchy. This study suggests that the 13 Combined DNA Index System (CODIS) markers and two added markers named D2S1338, D19S433 are highly informative and therefore suitable in matching biological specimen in human identification and population genetic study.

Deletions in the Y-derived amelogenin gene fragment in the Indian population.

BACKGROUND: Rare failures in amelogenin-based gender typing of individuals have been observed globally. In this study, we report the deletion of a large fragment of the amelogenin gene in 10 individuals out of 4,257 male samples analyzed from 104 different endogamous populations of India. METHODS: Samples were analyzed using commercial genetic profiling kits. Those that exhibited failures in amelogenin-based gender identification were further analyzed with published as well as newly designed primers to ascertain the nature and extent of mutation. RESULTS: The failure rate among Indian males was 0.23 %. Though the exact size and nature of the deletion (single point mutations at a number of positions or a single large deletion) could not be determined in the present study, it is inferred that the deletion spans a region downstream of the reverse primer-binding site of commercially available amelogenin primer sets. Deletions were conspicuously absent among the Mongoloid tribes of Northeast India, while both caste and tribal groups harbored these mutations, which was predominantly among the Y-chromosomes belonging to J2 lineage. CONCLUSION: Our study indicates that the different amelogenin primer sets currently included in genetic profiling multiplex kits may result in erroneous interpretations due to mutations undetectable during routine testing. Further there are indications that these mutations could possibly be lineage-specific, inherited deletions.

Antiquity, geographic contiguity and genetic affinity among Tibeto-Burman populations of India: a microsatellite study.

BACKGROUND: The Tibeto-Burman (TB) populations are one of the four major linguistic population groups of India. They are considered belonging to different stocks and show wide variation in culture and language; however, their genetic relationship, antiquity and migration history among the regional populations has been little investigated. Molecular genetic studies are expected to clearly show the antiquity and genetic diversity of these populations. AIM: This paper seeks to understand the extent and magnitude of genetic affinities and diversities among 14 TB populations (12 Indian and two global groups), investigate the findings based on classical genetic markers and verify the historical accounts of their migration and genetic history based on 12 microsatellite markers. SUBJECTS AND METHODS: The allele frequency data for 12 STR loci of 13 Asian (Tibeto-Burman) populations were obtained from the literature and the Adi Pasi data was obtained by microsatellite typing of their blood samples. The 12 loci studied are D5S818, FGA, D8S1179, D21S11, D7S820, CSF1PO, D3S1358, THO1, D13S317, vWa, TPOX, D18S51. Three different distance measures, two phylogenetic trees and PCA plot have been employed to understand the genetic relationship of the studied populations. RESULTS: Average heterozygosity values range from 68 to 79% and the average G(ST) value is 4.7%. The dendrogram, based on the D(A) distance, shows the clustering of populations based on their diversities and geographical contiguity; the Mizoram and Arunachal Pradesh populations especially cluster together, populations from Sikkim form a separate subcluster and Manipur populations along with the Garo of West Bengal separate out from the other clusters. The Harpending and Ward regression model shows isolated populations positioned below the regression line and others, who experience external gene flow, placed above the line. The results support folklore migration accounts of their possible antiquity with the Tibetan and southern Chinese populations. CONCLUSIONS: Overall, geographic contiguity, punctuated by isolating barriers, is a major influencing factor of genetic affinity among the TB population; contiguous populations within a region show greater genetic relationship than with distant TB populations over a wide geographical area. The results of the microsatellite study also support the history of diverse routes of migration of these populations.

Phylogeography of mitochondrial DNA and Y-chromosome haplogroups reveal asymmetric gene flow in populations of Eastern India.

Polymorphisms in mitochondrial (mt) DNA and Y-chromosomes of seven socially and linguistically diverse castes and tribes of Eastern India were examined to determine their genetic relationships, their origin, and the influence of demographic factors on population structure. Samples from the Orissa Brahmin, Karan, Khandayat, Gope, Juang, Saora, and Paroja were analyzed for mtDNA hypervariable sequence (HVS) I and II, eight Y-chromosome short tandem repeats (Y-STRs), and lineage-defining mutations diagnostic for Indian- and Eurasian-specific haplogroups. Our results reveal that haplotype diversity and mean pairwise differences (MPD) was higher in caste groups of the region (>0.998, for both systems) compared to tribes (0.917-0.996 for Y-STRs, and 0.958-0.988 for mtDNA haplotypes). The majority of paternal lineages belong to the R1a1, O2a, and H haplogroups (62.7%), while 73.2% of maternal lineages comprise the Indian-specific M*, M5, M30, and R* mtDNA haplogroups, with a sporadic occurrence of West Eurasian lineages. Our study reveals that Orissa Brahmins (a higher caste population) have a genetic affinity with Indo-European speakers of Eastern Europe, although the Y-chromosome data show that the genetic distances of populations are not correlated to their position in the caste hierarchy. The high frequency of the O2a haplogroup and absence of East Asian-specific mtDNA lineages in the Juang and Saora suggest that a migration of Austro-Asiatic tribes to mainland India was exclusively male-mediated which occurred during the demographic expansion of Neolithic farmers in southern China. The phylogeographic analysis of mtDNA and Y-chromosomes revealed varied ancestral sources for the diverse genetic components of the populations of Eastern India.

Molecular insights into the origins of the Shompen, a declining population of the Nicobar archipelago.

The Shompen, one of the most isolated and poorly understood contemporary hunter-gatherer populations, inhabit Great Nicobar Island, the southernmost island of the Nicobar archipelago. Morphological imprints in the Shompen were interpreted to favour a mixed Indo-Chinese, Malay, Negrito and Dravidian origin. Analyses of the mitochondrial, Y-chromosomal and autosomal gene pool of contemporary Shompen have revealed low diversity, illustrating a founder effect in the island population. Mitochondrial sequence analyses revealed the presence of two haplogroups of R lineage: B5a, and a newly defined clade, R12. Y-chromosomal analyses demonstrated the occurrence of a single lineage found predominantly in Austro-Asiatic speakers across Asia. With the different types of genetic markers analysed, the Shompen exhibit varying levels of genetic relatedness with the Nicobarese, and Austro-Asiatic speakers of mainland India and Southeast Asia. These genetic analyses provide evidence that the Shompen, an offshoot of the Nicobarese, are descendants of Mesolithic hunter-gatherers of Southeast Asian origin, deriving from at least two source populations.

Genetic polymorphism at 15 tetrameric short tandem repeat loci in four aboriginal tribal populations of Bengal.

POPULATIONS: This study reports the genetic polymorphism observed at 15 short tandem repeat loci D3S1358, TH01, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, CSF1PO, vWA, D8S1179, TPOX, D2S1338, D19S433, and FGA in four aboriginal populations of Bengal. The analysis was performed to decipher the suitability of CODIS as well as six other highly polymorphic and unlinked markers in Forensic Testing. Studied populations include four tribes: Karmali, Kora, Maheli, and Lodha.

A prehistory of Indian Y chromosomes: evaluating demic diffusion scenarios.

Understanding the genetic origins and demographic history of Indian populations is important both for questions concerning the early settlement of Eurasia and more recent events, including the appearance of Indo-Aryan languages and settled agriculture in the subcontinent. Although there is general agreement that Indian caste and tribal populations share a common late Pleistocene maternal ancestry in India, some studies of the Y-chromosome markers have suggested a recent, substantial incursion from Central or West Eurasia. To investigate the origin of paternal lineages of Indian populations, 936 Y chromosomes, representing 32 tribal and 45 caste groups from all four major linguistic groups of India, were analyzed for 38 single-nucleotide polymorphic markers. Phylogeography of the major Y-chromosomal haplogroups in India, genetic distance, and admixture analyses all indicate that the recent external contribution to Dravidian- and Hindi-speaking caste groups has been low. The sharing of some Y-chromosomal haplogroups between Indian and Central Asian populations is most parsimoniously explained by a deep, common ancestry between the two regions, with diffusion of some Indian-specific lineages northward. The Y-chromosomal data consistently suggest a largely South Asian origin for Indian caste communities and therefore argue against any major influx, from regions north and west of India, of people associated either with the development of agriculture or the spread of the Indo-Aryan language family. The dyadic Y-chromosome composition of Tibeto-Burman speakers of India, however, can be attributed to a recent demographic process, which appears to have absorbed and overlain populations who previously spoke Austro-Asiatic languages.

Molecular identification of lizard by RAPD & FINS of mitochondrial 16s rRNA gene.

In the present study, we identified the structure-less skeleton suspected to be of house lizard present in jaggery, consumption of which caused mass food poisoning using, RAPD (Random Amplification of Polymorphic DNA) with random primers and FINS (Forensically Informative Nucleotide Sequencing) with mitochondrial 16s rRNA gene. The NJ tree dendogram based on distance calculated from RAPD bands clearly identified the structure-less as Calotes versicolor (Garden Lizard). In FINS analysis of the mitochondrial 16s rRNA gene the NJ tree based on Kimura-2-parameter distance matrices clearly reveal that the unknown sample clustered with Agmidae family and closest to Calotes versicolor (Garden Lizard) with 100% bootstrap support, whereas all other species belong to Gekkonida family form a single distinct cluster including Hemidactylus fluviviridis (House Lizard). This is the first successful typing of mitochondrial 16s rRNA with FINS approach to identify the biological origin of a structure-less skeleton. Our analysis also sustained successful identification of unknown samples using RAPD method with optimized conditions in a laboratory setup with low resources.

Microsatellite diversity reveals the interplay of language and geography in shaping genetic differentiation of diverse Proto-Australoid populations of west-central India.

Microsatellite diversity was analyzed in four Proto-Australoid tribes, including Indo-European (Marathi)-speaking Katkari, Pawara, Mahadeo-Koli, and Dravidian (Gondi)-speaking groups of Maharashtra, west-central India, to understand their genetic structure and to identify the congruence between language and gene pool. Allele frequency data at 15 short tandem repeat (STR) loci in studied tribes was compared with data of 22 Indo-European- and Dravidian-speaking caste and tribal populations using heterozygosity, allele size variance, analysis of molecular variance (AMOVA), G(ST) estimate, PC plot, and Mantel correlation test. Our results demonstrate that "Gondi" tribes comprising the Madia-Gond, a hunter-gatherer population, and the agriculturist Dheria-Gond harbor lower diversity than "Marathi" tribal groups, which are culturally and genetically distinct. Katkari, a hunter-gatherer tribe, showed greater diversity and the presence of a large number of unique alleles, genetically distinct from all others except the Pawara, supporting their old cultural links. The agriculturist Pawara tribe represents a splinter subgroup of the Bhil tribe and has experienced gene flow. The Mahadeo-Koli, an agriculturally oriented tribe, displayed significant heterozygote deficiency, attributable to the practice of high endogamy. The Proto-Australoid tribal populations were genetically differentiated from castes of similar morphology, suggesting different evolutionary mechanisms operating upon the populations. The populations showed genetic and linguistic similarity, barring a few groups with varied migratory histories. The microsatellite variation clearly demonstrates the interplay of sociocultural factors including linguistic, geographical contiguity, and microevolutionary processes in shaping the genetic diversity of populations in contemporary India. This study supports the ethno-historical relationships of Indian populations.

Host microsatellite alleles in malaria predisposition?

BACKGROUND: Malaria is a serious, sometimes fatal, disease caused by Plasmodium infection of human red blood cells. The host-parasite co-evolutionary processes are well understood by the association of coding variations such as G6PD, Duffy blood group receptor, HLA, and beta-globin gene variants with malaria resistance. The profound genetic diversity in host is attributed to polymorphic microsatellites loci. The microsatellite alleles in bacterial species are known to have aided their survival in fatal environmental conditions. The fascinating question is whether microsatellites are genomic cushion in the human genome to combat disease stress and has cause-effect relationships with infections. PRESENTATION OF THE HYPOTHESIS: It is hypothesized that repeat units or alleles of microsatellites TH01 and D5S818, located in close proximity to beta-globin gene and immune regulatory region in human play a role in malaria predisposition. Association of alleles at aforesaid microsatellites with malaria infection was analysed. To overrule the false association in unrecognized population stratification, structure analysis and AMOVA were performed among the sampled groups. TESTING OF HYPOTHESIS: Associations of microsatellite alleles with malaria infection were verified using recombination rate, Chi-square, and powerful likelihood tests. Further investigation of population genetic structure, and AMOVA was done to rule out the confounding effects of population stratification in interpretation of association studies. IMPLICATION OF THE HYPOTHESIS: Lower recombination rate (theta) between microsatellites and genes implicated in host fitness; positive association between alleles-13 (D5S818), 9 (TH01) and strong susceptibility to Plasmodium falciparum; and alleles-12 (D5S818) and 6 (TH01) rendering resistance to human host were evident. The interesting fact emerging from the study was that while predisposition to malaria was a prehistoric attribute, among TH01 alleles; evolution of resistant allele-6 was a recent phenomenon, which could conceivably be driven by infection related selective forces. The host's microsatellite allelic associations with malaria infection were valid in the light of low genetic variance between sampled groups and no population stratification.