Application of new generation tools for better disease diagnosis and to understand molecular mechanism of biological systems.

Abstract : A low level of high-density lipoprotein cholesterol (HDL-C) is common and an important marker for increased cardiovascular risk. Many patients with abnormal HDL-C have a rare mutation in one of several genes, but molecular diagnosis is rarely performed in clinical practice. We investigated the accuracy and diagnostic yield of a targeted next-generation sequencing (NGS) assay for extreme levels of HDL-C. We developed a targeted NGS panel to capture the exons, intron/exon boundaries and untranslated regions of 26 genes with highly penetrant effects on plasma lipid levels. We sequenced 141 patients with extreme HDL-C levels and found good diagnostic yield as well as specificity.

Doxorubicin is one of the most widely used anti-cancer drugs with high number of cardiotoxicity incidence. Genome-wide association studies have identified some genetic variants associated with cardiotoxicity and further studies are required to understand the role of these genetic variants. We are applying CRISPR-Cas9 technology to introduce these genetic variants for understanding doxorubicin induced cellular toxicity.