摘要

追獵疾病的致病基因以找尋病痛的本質然後治癒是我們的目標。全外顯子體測序是一個強大的工具，可以比全基因體測序技術較低的成本來得到周圍目標區域的DNA序列。序列排比和變異點呼叫這些工具幫助我們從龐大的原始 DNA 數據進行分析找出單核苷酸變異（ SNV ）和插入/缺失（INDEL）的變異。病竇症候群的特點是竇性停搏，房顫和房室傳導干擾。我們使用譜系基因型的方法來研究一個有病竇症候群包含3代成員的家庭。我們以此譜系基因型的方法縮減可能相關變異至很小一部份。經由變異點註解和聚合酶鏈反應（PCR ）驗證後，我們發現了一個新的SNV位於LMNA基因，它是內核膜蛋白纖層蛋白 A/C 的基因。蛋白結構模擬預測此突變點可能會影響LMNA功能。

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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