Genomic congruence of Indo-European speaking tribes of western India with Dravidian-speaking populations of southern India: A study of 20 autosomal DNA markers.

BACKGROUND: Due to its geographic location, Gujarat has played a major role in assimilation of different cultures with those of the subcontinent of India and is home to a number of Indo-European speaking tribes. AIM: This study examined the genetic structure and extent of gene differentiation in eight Indo-European speaking tribal populations of southern Gujarat in western India. It also determined if there was any residual effect of linguistic and cultural assimilation of Indo-European speaking groups on the genomic profile of the tribes under study. METHODS: Twenty autosomal DNA markers (Alu InDels and Restriction Fragment Length Polymorphisms) were analysed. RESULTS AND CONCLUSIONS: Average heterozygosity levels were high and degree of gene differentiation (G(ST) = 2%) was small, indicating that genetic drift may not have played a major role in bringing out a characteristic genetic differentiation in these groups. The genetic structure of the populations revealed that neither of these groups was overtly admixed nor completely isolated. Other analyses undertaken on the population affiliations revealed only a slight influence of Indo-European speaking populations on the tribal groups of Gujarat, but there was an overwhelming influence of Dravidian speaking groups of southern India, suggesting that genetic affinities may not necessarily be dependent on linguistic similarities.

The Prevalence of Factor V Leiden (G1691A) and Methylenetetrahydrofolate Reductase C677T Mutations in Sickle Cell Disease in Western India.

The prevalence of the Factor V Leiden (FVL; G1691A) mutation and the methylenetetrahydrofolate reductase (MTHFR; C677T) mutation was determined in 180 patients with sickle cell (SS) disease (126 sickle homozygous and 54 sickle ß-thalassaemia--age 1-47 years) and in 130 healthy controls. The FVL mutation in the heterozygous state was present in only 3 patients with SS disease and was absent in the controls. Genotyping of MTHFR 677C > T revealed increased frequency of the C allele than the T allele in patients as well as in controls. This suggests that these genetic markers may not be major risk factors for a hypercoagulable state in Indian patients with SS disease.

Y chromosome haplogroup distribution in Indo-European speaking tribes of Gujarat, western India.

The present study was carried out in the Indo-European speaking tribal population groups of Southern Gujarat, India to investigate and reconstruct their paternal population structure and population histories. The role of language, ethnicity and geography in determining the observed pattern of Y haplogroup clustering in the study populations was also examined. A set of 48 bi-allelic markers on the non-recombining region of Y chromosome (NRY) were analysed in 284 males; representing nine Indo-European speaking tribal populations. The genetic structure of the populations revealed that none of these groups was overtly admixed or completely isolated. However, elevated haplogroup diversity and FST value point towards greater diversity and differentiation which suggests the possibility of early demographic expansion of the study groups. The phylogenetic analysis revealed 13 paternal lineages, of which six haplogroups: C5, H1a*, H2, J2, R1a1* and R2 accounted for a major portion of the Y chromosome diversity. The higher frequency of the six haplogroups and the pattern of clustering in the populations indicated overlapping of haplogroups with West and Central Asian populations. Other analyses undertaken on the population affiliations revealed that the Indo-European speaking populations along with the Dravidian speaking groups of southern India have an influence on the tribal groups of Gujarat. The vital role of geography in determining the distribution of Y lineages was also noticed. This implies that although language plays a vital role in determining the distribution of Y lineages, the present day linguistic affiliation of any population in India for reconstructing the demographic history of the country should be considered with caution.

Distribution of beta-globin haplotypes among the tribes of southern Gujarat, India.

The present study was carried out in Indo-European speaking tribal population groups of southern Gujarat (India) to elucidate the allelic and haplotypic content of ß-globin system in individuals with HbAA genotypes. 6 neutral restriction sites of the ß-globin system were analysed and various statistical parameters were estimated to draw meaningful interpretations. All the 6 sites were found to be polymorphic and most were in Hardy-Weinberg Equilibrium in the studied group. Haplotypes were constructed using two different combinations of the 6 restriction sites analysed. Analysis of the 5 sites revealed a set of three predominant haplotypes, '+----', '-++-+' and '-+-++'; and haplotypes '+--', '++-' and '+++' were found to be the most frequent when the 3 sites were used to construct the haplotypes. Haplotypic heterozygosity levels (>83%) observed in the present study group were comparable to those observed in African and Afro-American populations and greater than other world populations. All the ancestral haplotypes, +-----, -++-+, -+-++ and ----+ were found in the study group. The distribution pattern of various haplotypes was consistent with the global pattern. The paucity of comparable data from other Indian populations restricted one from making interpretations about the study group's relationships with other Indian populations but the results were indicative of older population histories or experience of gene flow by the study group and their affinities with populations of southern India.

The Fc receptor polymorphisms and expression of neutrophil activation markers in patients with sickle cell disease from Western India.

OBJECTIVE: Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. METHODS: In this paper 127 sickle cell anemia patients and 58 patients with sickle-ß-thalassemia (median age 12 ± 8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. RESULTS: The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312). CONCLUSION: The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

Genomic and linguistic affinities: a study of allelic and haplotype diversity at DRD2 locus among the tribes of Gujarat, western India.

Do genetic and linguistic affinities necessarily go hand in hand? An attempt has been made in the present work to explore this dimension of population structure using three evolutionarily important TaqI sites (TaqI A, TaqI B, and TaqI D) on the dopamine receptor D2 (DRD2) locus. For the first time, DNA samples from 612 unrelated individuals belonging to 11 Indo-European-speaking tribal population groups of Gujarat, western India, have been analyzed for these three sites. All the three sites are found to be polymorphic with greater interpopulation variation seen at the TaqI B site. The average heterozygosity for the haplotype system has been found to be high in the populations under study. Most of the populations share six of the eight haplotypes pointing toward underlying genetic uniformity, which is further reaffirmed by regression analysis of heterozygosity on genetic distance. The frequency of ancestral haplotype B2D2A1 is found to range between 1.9% and 15.9%. Linkage disequilibrium between TaqI B and TaqI D sites and between TaqI B and TaqI A sites is statistically significant in all but one population. Our findings reveal strong affinities between Indo-European-speaking tribal groups of Gujarat and Dravidian-speaking tribal groups of South India, suggesting that genetic affinities may not necessarily be dependent on linguistic similarities.