Screening for Copy Number Variation in Genes Associated with Atrial Fibrillation

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Atrial fibrillation (AF) is now recognized to be the most common sustained cardiac arrhythmia and a major public health burden. Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to play an important role in genetic susceptibility to common disease. Both linkage analysis and genetic association studies have shown that some genetic variants in the genes encoding for subunits of potassium or sodium channels are associated with familial and common AF. We hypothesized that the CNVs involving the genes encoding for subunits of potassium or sodium channels may play an important role in the pathophysiology and the susceptibility of AF. The goal of this proposal is to utilize a candidate genes case-control approach to demonstrate that CNVs affecting subunits of potassium or sodium channels genes are associated with risk of AF. To achieve this goal, five specific aims are proposed and going to be conducted in the following three years: 1. Using the Multiplex Ligation-dependent Probe Amplification (MLPA) to detect CNVs in the exons of KCNQ1, KCNE1, KCNH2, KCNE2, and SCN5A genes to determine the association between the CNVs of these genes and the risk of AF among Taiwanese. 2. Using the quantitative multiplex PCR of short fluorescent fragment (QMPSF) to confirm the indentified abnormal exon copy numbers. 3. Using the Array-based comparative genomic hybridization (CGH) analysis to further map the genomic rearrangement. 4. Using a DNA pooling approach for array CGH to investigate the presence of CNVs associated with AF in Taiwanese population 5. Using the patch clamp technique to determine whether the identified CNVs are functional variants. It is hoped that our study could identify novel genetic risk factors in our Taiwanese population and also help elucidate the mechanism of atrial fibrillation.

Project IDs

Project ID:PC10108-0732
External Project ID:NSC101-2314-B182-072
StatusFinished
Effective start/end date01/08/1231/07/13

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