全面性基因異常檢測的整合性平台之建置

Abstract

遺傳性疾病主要是由於基因體異常所造成，帶有缺陷的基因會經由父母 遺傳給下一代，除此之外，也可能因為異常的減數分裂導致配子攜帶錯誤 的染色體，而生下不正常的嬰兒。遺傳性疾病的致病基因之變異型式與成 因相當複雜，而且新發現的致病突變一直在增加；隨著人類對基因體的了 解越來越深入，基因與遺傳性疾病相關性方面的知識也越來越豐富，加上 各種生化檢測技術以及生物資訊學的蓬勃發展，基因檢測方法也越來越多， 基於不同的基因檢測方法皆有其適用性與侷限性，如何能有效地作全面性 基因檢測一直是努力的目標。 本研究評估各種遺傳性疾病檢測技術的優勢與缺點後，策略性地選擇幾 項基因檢測技術，整合成有效且符合經濟效益的全面性遺傳性疾病基因檢 測平台，此整合性平台包括：一、基因型分型晶片(genotyping array)，二、 次世代定序法(next generation sequencing, NGS)之標的基因片段定序 (targeted resequencing)以及三、偵測短縱列重複序列(short tandem repeats, STRs)之生物技術(biotechnology)搭配 DNA 分析儀(DNA analyzer)。 經過此整合性平台的檢測，本研究將結合生物資訊的分析技術進行判讀、 分析與註解，並針對各項檢測技術的輸出資料設計分析流程，使最終能直 觀地讀取基因檢測結果之訊息。 此研究歸納各種遺傳性疾病的突變型式，並蒐集各種型式中幾種常見的 遺傳性疾病的基因突變資料作檢測項目案例，最後透過研究案例來模擬此 平台之實際使用成果。

Genetic diseases are mainly causing by bringing defective genome which comes from parents or the abnormal mitosis, so that lead to give birth to abnormal infant. Genome mutation types and causes of pathogenic genes which cause genetic disease are very complicated; novel discovered mutation also has been increasing. With more understanding of the human genome and the relationship between genome and genetic diseases, moreover, developing of a variety of iochemical detection techniques and bioinformatics, create many genetic testing techniques. Based on every genetic testing methods have their applicability and limitations, how to be effective for comprehensive genetic testing has been a target. In this study, we assess the advantages and drawbacks of a variety of genetic disease-detection techniques; strategically select certain genetic disease detection techniques, integrated into an effective and cost-effective of the comprehensive genetic diseases detection platform. This integrated platform consists of (1) genotyping array, (2) targeted resequencing through next generation sequencing, (3) short tandem repeats detection technique by biotechnology and DNA Analyzer. After detecting by the integrated platform, this study also combines with bioinformatics software and web tool for interpretation, analysis and annotation, moreover, design the analysis flow for output data of the detection platforms.