5 research outputs found
In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes
YesSingle nucleotide polymorphisms (SNPs) in PLCE1
and MICB genes increase risk for the development of dengue
shock syndrome (DSS). We used Bioinformatics tools to predict
alterations at the transcriptional and posttranslational levels
driven by PLCE1 and MICB SNPs associated with DSS.
Functional and phenotypic analysis conducted to determine
deleterious SNPs and impact of amino acid substitution on
the structure and function of proteins identified rs2274223
(H1619R) as deleterious to protein coding as it induces structural
change in the C2 domain of PLCε, with the mutant residue
more positively charged than the wild-type residue (RMSD
score, 1.75 Ă…).Moreover, rs2274223 condenses the chromatinrepressing
PLCε expression in DSS. Briefly, this study presents
the impact of a single nucleotide transition at SNPs associated
with DSS on differential protein binding patterns with PLCE1
and MICB genes and on protein structure modification and their
possible role in the pathogenesis of DSS
Human aging in the post-GWAS era: further insights reveal potential regulatory variants
NoHuman aging involves a gradual decrease in cellular integrity that contributes to multiple complex disorders such as neurodegenerative disorders, cancer, diabetes, and cardiovascular diseases. Genome-wide association studies (GWAS) play a key role in discovering genetic variations that may contribute towards disease vulnerability. However, mostly disease-associated SNPs lie within non-coding part of the genome; majority of the variants are also present in linkage disequilibrium (LD) with the genome-wide significant SNPs (GWAS lead SNPs). Overall 600 SNPs were analyzed, out of which 291 returned RegulomeDB scores of 1-6. It was observed that just 4 out of those 291 SNPs show strong evidence of regulatory effects (RegulomeDB score < 3), while none of them includes any GWAS lead SNP. Nevertheless, this study demonstrates that by combining ENCODE project data along with GWAS reported information will provide important insights on the impact of a genetic variant-moving from GWAS towards understanding disease pathways. It is noteworthy that both genome-wide significant SNPs as well as the SNPs in LD must be considered for future studies; this may prove to be crucial in deciphering the potential regulatory elements involved in complex disorders and aging in particular