ABSTRACT
Long QT Syndrome (LQTS), a disorder of the cardiac repolarization process with prolongation of the QT interval (QTc ≥0.46 seconds), is an ion-channelopathy. Mutations in either KCNQ1 or KCNE1 genes are susceptible to LQTS. Hence, screening of KCNQ1 and KCNE1 genes is taken up to evaluate the genetic correlation of these genes in Long QT patients of Indian origin. A total of 33 Long QT Syndrome patients and 100 healthy subjects were enrolled for the present study. PCR-SSCP protocol was utilised for screening of KCNQ1 and KCNE1 genes followed by In-silico and statistical analysis. The clinical profile of the Long QT syndrome patients in our study revealed a higher percentage of females with the mean age also being higher in females when compared to males. The two variations (S546S and IVS13+36A>G) in KCNQ1 and the S38G polymorphism in KCNE1 gene were identified and their association with Long QT syndrome is being reported for the first time in Indian population. S546S is located in the KCNQ1 C terminus close to this domain and IVS13+36A>G is located in the intronic region in close proximity to the coding region for C-terminal domain; these may therefore affect the functional protein through non-assembly. S38G leads to a substitution of serine to glycine at 38th amino acid position (S38G) in the transmembrane domain of KCNE1. Our study reports compound heterozygosity/genetic compound ofS546S and IVS13+36A>G of KCNQ1 gene. Haplotype frequencies and linkage disequilibrium analysis revealed a significant association between the three biomarkers. Compound heterozygosity of the polymorphisms influence downstream signalling and KCNQ1- KCNE1 interactions.
ABSTRACT
Transposable elements (TEs) represent genome’s dynamic component, causing mutations and genetic variations. Transposable elements can invade eukaryotic genomes in a short span; these are silenced by homology-dependent gene silencing and some functional parts of silenced elements are utilized to perform novel cellular functions. However, during the past two decades, major interest has been focused on the positive contribution of these elements in the evolution of genomes. The interaction between mobile DNAs and their host genomes are quite diverse, ranging from modifications of gene structure to alterations in general genome architecture and can be regarded as hidden magicians in shaping evolution of genomes. Some of the prominent examples that impressively demonstrate the beneficial impact of TEs on host biology over evolutionary time include their role in structure and functions of eukaryotic genomes.