A novel subgroup Q5 of human Y-chromosomal haplogroup Q in India

BACKGROUND: Y-chromosomal haplogroup (Y-HG) Q is suggested to originate in Asia and represent recent founder paternal Native American radiation into the Americas. This group is delineated into Q1, Q2 and Q3 subgroups defined by biallelic markers M120, M25/M143 and M3, respectively. Recently, a novel subgroup Q4 has been identified which is defined by bi-allelic marker M346, representing HG Q (0.41%, 3/728) in Indian population. With scanty details of HG Q in Asia, especially India, it was pertinent to explore the status of the Y-HG Q in Indian population to gather an insight to determine the extent of diversity within this region. RESULTS: We observed 15/630 (2.38%) Y-HG Q individuals in India with an ancestral state at M120, M25, M3 and M346 markers, indicating an absence of already known Q1, Q2, Q3 and Q4 sub-haplogroups. Interestingly, we further observed a novel 4 bp deletion/insertion polymorphism (ss4 bp, rs41352448) at 72,314 position of human arylsulfatase D pseudogene, defining a novel sub-lineage Q5 (in 5/15 individuals, i.e., 33.3 % of the observed Y-HG Q) with distributions independent of the social, cultural, linguistic and geographical affiliations in India. CONCLUSION: The study adds another sublineage Q5 in the already existing arrangement of Y-HG Q in literature. It was quite interesting to observe an ancestral state Q* and a novel sub-branch Q5, not reported elsewhere, in Indian subcontinent, though in low frequency. A novel subgroup Q4 was identified recently which is also restricted to Indian subcontinent. The most plausible explanation for these observations could be an ancestral migration of individuals bearing ancestral lineage Q* to Indian subcontinent followed by an autochthonous differentiation to Q4 and Q5 sublineages later on. However, other explanations of, either the presence of both the sub haplogroups (Q4 and Q5) in ancestral migrants or recent migrations from central Asia, cannot be ruled out till the distribution and diversity of these subgroups is explored extensively in Central Asia and other regions

The Interactive Effect of <em>SIRT1</em> Promoter Region Polymorphism on Type 2 Diabetes Susceptibility in the North Indian Population

<div><p>Our previous studies have implicated genes mainly involved in the activity of pancreatic β cells in type 2 diabetes (T2D) susceptibility in the North Indian population. Recent literature on the role of <em>SIRT1</em> as a potential master switch modulating insulin secretion and regulating gene expression in pancreatic β cells has warranted an evaluation of <em>SIRT1</em> promoter region polymorphisms in the North Indian population, which is the main focus of the present study. 1542 samples (692 T2D patients and 850 controls) were sequenced for the 1.46 kb region upstream the translation start site of the <em>SIRT1</em> gene. We performed a functional characterization of the <em>SIRT1</em> promoter region polymorphisms using luciferase assay and observed a single-nucleotide polymorphism (SNP), rs12778366, in association with SIRT1 expression. We propose that TT, the high-expressing genotype of SNP rs12778366 in the <em>SIRT1</em> promoter region and present in >80% of the North Indian population, was favored under conditions of feast-famine cycles in evolution, which has turned out to be a cause of concern in the present sedentary lifestyle under <em>ad libitum</em> conditions. Case-control association analysis did not implicate rs12778366 in T2DM per se in the studied population. However, our earlier reported risk genotype combinations of mt-<em>ND3</em>, <em>PGC1α</em>, and <em>UCP2</em>-866, when compared with the protective genotype combinations, in the background of the high-expressing TT genotype of <em>SIRT1</em> SNP rs12778366, showed a very high additive risk [corrected odd ratio (OR) = 8.91; p = 6.5×10⁻¹¹]. The risk level was considerably low in the genotype backgrounds of TX (OR = 6.68; p = 2.71×10⁻¹²) and CX (OR = 3.74; p = 4.0×10⁻³). In addition, we screened other reported T2D-associated polymorphisms: <em>PIK3R1</em> rs3730089, <em>IRS1</em> rs1801278, and <em>PPP1R3</em> rs1799999, which did not show any significant association in North Indian population. The present paper emphasizes the importance of gene interactions in the biological pathways of T2D, a complex lifestyle disease.</p> </div

The observed relative luciferase activities.

<p>The relative activities of the haplotypes (with alleles at rs12778366 T>C, rs3758391 T>C and rs35706870 A>C, respectively) are shown. Combinations of: mutant (M) at rs12778366 with rest wild (W) i.e., MWW = ‘CTA’; mutant at rs3758391 and rest wild i.e., WMW = ‘TCA’ ; and mutant at rs35706870 with rest wild i.e., WWM = ‘TTC’ were compared against all wild i.e., WWW = ‘TTA’.</p

Promoter region of <i>SIRT1</i> gene.

<p>Figure provides the details of the 11 promoter polymorphisms of the <i>SIRT1</i> gene spanned through 1.46 kb region upstream the translation start site. 4 SNPs marked by ‘X’ did not show polymorphism in the studied population. D′ values are plotted as a graph to show linkage disequilibrium between the 7 observed polymorphic markers. Frequencies of the observed haplotypes and details of the picked Tag SNPs and respective alleles captured among the 7 polymorphic markers are also provided.</p