Robertsonian translocation (RT) involves the end-to-end fusion of two acrocentric chromosomes. RT between chromosome 21 and any other acrocentric chromosome can lead to infertility, early pregnancy miscarriages or the birth of a Down syndrome (DS) baby in silent carriers. DS is a genetic disorder characterised by distinct physical features and some degree of cognitive disability. Mainly there are three cytogenetic forms of DS – full trisomy 21, mosaic trisomy 21 and RT trisomy 21. However, genetic counselling and targeted prenatal diagnostic testing can help RT carriers give birth to a normal baby. With this, we present a case report where preconception and prenatal genetic counselling and testing helped a RT Carrier female give birth to a healthy child.
In Figs 1-5, the figure panel labels are missing.Please see the corrected Figs 1-5 here.Fig 1. Concentration dependency of CPF on C3H10T½ MSC viability.(A) CPF at concentrations 0.01, 0.1, 1
The present study aims to examine the association of tumor necrosis factor-α (TNF-α) g.-308 G > A and adiponectin (ADIPOQ) g. + 45 T > G gene polymorphisms in type 2 diabetes (T2D) and its microvascular complications diabetic retinopathy (DR) and diabetic nephropathy (DN).A total of 672 individuals were analysed from the North-West population of Punjab. Genotyping was accomplished by a combination of allele specific amplification refractory mutation system and restriction digestion for TNF-α g. - 308 G > A and ADIPOQ g. + 45 T > G polymorphisms, respectively. Further, in silico modeling was done to predict secondary structure of mRNA for g. + 45 T > G polymorphism in the ADIPOQ gene by RNA fold.The minor allele frequency observed in the controls for the TNF-α G > A and ADIPOQ T > G polymorphisms were 0.07 and 0.10, respectively. The results show no significant association with TNF-α g. - 308 G > A polymorphism in T2D as well as in any of the microvascular complication. However, the ADIPOQ g. + 45 T > G polymorphism shows significant association in T2D (p = 0.048) and DR (p = 0.001) but in DN patients, no association was observed. Interactive analysis revealed that the two polymorphisms jointly conferred a 1.45-fold risk towards the occurrence of T2D [p = 0.031; OR = 1.45 (1.03-2.05)]. In the secondary structure of mRNA, slight free energy change was observed between the wild ( - 1370.28 kcal/mol) and variant allele (-1369.08 kcal/mol).Our results indicated a higher risk of T2D and DR in the background of ADIPOQ TT genotype. Further, the ADIPOQ g. + 45 T > G and TNF-α g. - 308 G > A polymorphisms jointly give 1.45-fold risk towards T2D.
Summary Calpain 10 ( CAPN10 ) variants have been associated with the genetic susceptibility to type 2 diabetes (T2D). In the present case-control study, we analysed the distribution of SNP-19 insertion/deletion (I/D) polymorphism in a total of 607 samples (103 T2D cases and 102 healthy controls) from Brahmin; (100 T2D cases and 100 healthy controls) from Bania and (100 T2D cases and 102 healthy controls) from Jat Sikh ethnic groups of the North-West Indian population. Increased frequency of I allele and II genotype was found in T2D in Brahmin ethnic group [ P = 0·003, OR = 2·83 (1·43–5·61 at 95% CI)]. Significant correlation between II genotype and body mass index (BMI) was also observed [ P = 0·003, OR = 3·31 (1·52–7·20 at 95% CI)]. No association for the genotypes and alleles was seen in Banias and Jat Sikhs. Our data suggests that SNP-19 I/D variation in the CAPN10 gene is modulated by ethnicity and influences the susceptibility to T2D in the North-West Indian population. We also performed a meta-analysis of relevant studies to assess the validity of this association. Data from 13 case-control studies with 15 760 samples comprising of 8395 T2D cases and 7365 controls were finally analysed. Significant heterogeneity between individual studies was evident in dominant and codominant models. The results of present meta-analysis indicate an association of T2D with carriers of DD genotype of CAPN10 I/D polymorphism. However, further analyses on a larger sample size are required to establish a conclusive association in meta-analysis.
Geographic and ethnic differences impart an immense influence on the genetic susceptibility to Type 2 diabetes (T2D) and diabetic nephropathy (DN). Transforming growth factor-beta1 (TGF-β1), a ubiquitously expressed pro-fibrotic cytokine plays a pivotal role in mediating the hypertrophic and fibrotic manifestations of DN. The present study is aimed to study the association of TGF-β1 g.869T>C (rs1800470) and g.-509C>T (rs1800469) polymorphism in T2D and end stage renal disease (ESRD) cases from the two geographically and ethnically different populations from North India. A total of 1313 samples comprising 776 samples from Punjab (204 with ESRD, 257 without ESRD, and 315 healthy controls) and 537 samples from Jammu and Kashmir (150 with ESRD, 187 without ESRD, and 200 controls) were genotyped for TGF-β1 (rs1800470 and rs1800469) using ARMS-PCR. The CC genotype of rs1800470 increased ESRD risk by 3.1-4.5-fold in both populations. However, for rs1800469, the TT genotype provided 5.5-fold risk towards ESRD cases from Jammu and Kashmir and no risk for the cases from Punjab. The haplotype C-T conferred nearly a 2-3-fold risk towards T2D and ESRD and diplotype CC-CT conferred a 4-fold risk towards ESRD. Our results conclude that TGF-β1 (rs1800470) may increase the risk of both ESRD and T2D in both populations, but TGF-β1 (rs1800469) provided risk for only ESRD in the population of Jammu and Kashmir. The present study is one of the large sample sized genetic association studies of T2D and ESRD from Indian population and adds to the scholarship on global health omics.
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 SIRT1 as a potential master switch modulating insulin secretion and regulating gene expression in pancreatic β cells has warranted an evaluation of SIRT1 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 SIRT1 gene. We performed a functional characterization of the SIRT1 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 SIRT1 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 ad libitum 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-ND3, PGC1α, and UCP2-866, when compared with the protective genotype combinations, in the background of the high-expressing TT genotype of SIRT1 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: PIK3R1 rs3730089, IRS1 rs1801278, and PPP1R3 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.
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