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The pedigree-genotype method to find candidate variants of Mendelian disease with whole exome sequencing
Dissertation

The pedigree-genotype method to find candidate variants of Mendelian disease with whole exome sequencing

Lai, Chun Chi
Doctor of Philosophy (PHD), 國立清華大學, 資訊工程學系
2013

Abstract

病竇症候群 全外顯體測序 LMNA 基因 短序列排比 變異點呼叫 變異點註解 連鎖分析 蛋白結構模擬 Sick Sinus Syndrome whole exome sequencing LMNA gene short reads alignment variants calling variants annotation linkage analysis protein structure modeling
ABSTRACT The Mendelian disease genes’ hunting is our goal to discover the nature of the illness and try to find a way to cure it. Exome sequencing is a powerful tool to characterize DNA sequences surrounding target regions at a much lower cost compared to the whole genome sequencing technique. The Single Nucleotide Variation (SNV) and insertion/deletion (Indel) variants called with the sequence alignment tools and variants calling tools are big raw data for the analysis. We use the pedigree-genotype method to investigate 3 generations of a Chinese family with SSS that was characterized by sinus arrest, atrial fibrillation and atrioventricular conduction disturbance. We narrowed down the variants to a small set with the pedigree-genotype method. Following with the annotation and the polymerase chain reaction (PCR) verification, we identified a novel SNV located in LMNA gene, which encodes the inner nuclear membrane protein lamin A/C. Structural modeling predicts the mutation may affect LMNA function.

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