Whole Exome Sequencing Approach to Identify Genetic Variants Causing Sudden Unexplained Death Syndrome

摘要

Channelopathies underlie the majority of pathogenic causes for sudden unexplained death syndrome (SUDS). Molecular autopsy is typically able to diagnose about one third of all SUDS cases with no other explainable cause[1]. There are some indications suggesting that channelopathies may be polygenic in cause, although there are no direct supportive evidence in the literature[2]. We hypothesize that arrhythmias leading to SUDS are the outcome of the combinatorial effect of several variants. The SUDS cases (n=22) were Chinese males who were below 40 years of age (excluding infants cases), associated with no known illness (acute or chronic) or heavy physical activities at time of death. The control population comprised 23 healthy, Chinese males who were age matched for comparison. Paired-end exome sequencing was performed using Illumina HiSeq2000 and TruSeq exome enrichment. Sequence alignment was carried out using BWA-SW[3], and variant calls using Genome Analysis Toolkit (GATK) HaplotypeCaller with annotations by SnpEff[4].