摘要
本論文的目的是將次世代定序方法應用於台灣族群的廣泛性帶因者篩檢。傳統的產前和孕前帶因者篩檢只針對特定族群中，盛行率高的特定疾病。這種方式基於種族背景和特定疾病的帶因者篩檢，在現代世界，因為族群融合迅速，往往不夠全面。其次，傳統方式需要多種評估方法來配合，才能處理多種狀況，這增加了孕前帶因者篩檢的複雜性，嚴重限制了篩檢覆蓋範圍。 使用次世代定序，上述的局限性得到大幅度的改善。它可以擴大所涵蓋的疾病基因數量並將檢測應用於跨族群的範圍。在這項研究中，我們建立一個涵蓋270基因的虛擬套組，應用臺灣生物資料庫裏的1496個全基因定序樣本予以分析各個單基因遺傳疾病的帶因率。我們發現，在台灣族群，23對父母中有1對可以得利於此項檢查，避免新生兒單基因遺傳疾病的風險。我們建議，利用次世代定序施行廣泛性帶因者篩檢，與傳統方式和陣列基因分型相比，可以提供更準確全面的資訊。瞭解個人單基因遺傳疾病帶因者者狀態不僅在生殖策略中很重要，而且在健康管理中也很重要。
並列摘要
The purpose of this thesis is to apply next-generation sequencing methods to expanded carrier screening(CS) in Taiwan. Traditional prenatal and preconception CS targeted specific diseases with high prevalence in defined subpopulations. CS based on ethnicity and race is often incomprehensive in the modern world due to complex population admixture. Second, multiple evaluation methods are required to process all these conditions, which contribute to the complexity of preconception screening. The technical limitation severely restricts the disease coverage in CS. Modern genetic screening technology using NGS overcomes the limitations mentioned above by expanding the number of diseases covered and applies the testing to whole populations. In this study, a 270- gene virtual panel is applied to 1496 individual WGS samples from Taiwan biobank. 1 in 23 couples in Taiwan might benefit from this method to avoid diseased offspring. We demonstrated next-generation sequencing, offered in a pan-ethnic approach, is a better way to carrier screening. It provides more comprehensive information in a broader range on reproduction choice compared to the traditional way and array genotyping. Knowing individual carrier status is important not only in reproduction, but also in health management.