Identification of deleterious synonymous variants in human genomes.

Motivation: The prioritization and identification of disease-causing mutations is one of the most significant challenges in medical genomics. Currently available methods address this problem for non-synonymous single nucleotide variants (SNVs) and variation in promoters/enhancers; however, recent research has implicated synonymous (silent) exonic mutations in a number of disorders.

Results: We have curated 33 such variants from literature and developed the Silent Variant Analyzer (SilVA), a machine-learning approach to separate these from among a large set of rare polymorphisms.

Factors influencing participation in a population-based biorepository for childhood heart disease.

Background: Consenting minors for genetics research and biobanking involves ethical and social challenges. We examined factors influencing participation rates in a population-based biorepository for childhood heart disease.

Methods: Individuals were prospectively enrolled across 7 centers in Ontario by using a standardized consent form.

Cardiac Troponin T (TNNT2) mutations are less prevalent in Indian hypertrophic cardiomyopathy patients.

We sought to determine the frequency of the genetic variations in the Troponin T (TNNT2) gene and its association in Indian cardiomyopathy patients. Sequencing of the entire TNNT2 gene in 162 hypertrophic cardiomyopathy (HCM) patients, along with 179 healthy controls, revealed a total of 15 variants. These included an A28V missense mutation, a novel single-nucleotide polymorphism (SNP) (g.

An association study of thrombospondin 1 and 2 SNPs with coronary artery disease and myocardial infarction among South Indians.

Introduction: Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A → G, rs2228262) and TSP-2 un-translated region (UTR) (3949T → G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study.

Differential expression of TNF-α signaling molecules and ERK1 in distal and proximal colonic tumors associated with obesity.

Distal and proximal colon cancers have been recognized as two different disease types in human population. The environmental factors involved in the pathogenesis of the proximal and distal tumors also differ. The main objective of this study was to determine if obesity-augmented colonic tumors differ from each other if they are located in different regions of the colonic axis.

Haplotypes on 9p21 modify the risk for coronary artery disease among Indians.

The chromosomal region 9p21 has been reported to be associated with myocardial infarction, coronary artery disease (CAD), diabetes, and many other related multifactorial diseases in humans. Although the genome-wide association studies have identified a limited number of single-nucleotide polymorphisms (SNPs) at 9p21 for CAD risk, the role of flanking SNPs has not been studied so far. Therefore, in the present work, we studied the role of flanking SNPs with respect to that of the previously identified SNPs rs10757278 and rs2383207 at 9p21 among the Indian subjects found to have CAD (n = 414) along with age- and sex-matched control subjects (n = 408).

Associations for lipoprotein lipase and peroxisome proliferator-activated receptor-gamma gene and coronary artery disease in an Indian population.

Background And Aims: Peroxisome proliferator activated receptor-gamma (PPARgamma) and lipoprotein lipase (LPL) genes are important in pathways of triglyceride metabolism, insulin resistance and adipogenesis. We hypothesized that polymorphisms of PPARgamma Pro12Ala, LPL HindIII and LPL Ser447X influence severity of coronary artery disease (CAD) in an Indian population.

Methods: PPARgamma Pro12Ala, LPL HindIII and LPL Ser447X polymorphisms were genotyped in 414 patients with CAD and matched with 424 controls.

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians.

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population.