台灣族群全基因組劑量變異分析：建立供作臨床與研究應用的數據資料

Abstract

基因組劑量變異(Copy Number Variation)是人類遺傳變異的主要來源，它會造成孟德爾遺傳性狀、散發性性狀，可能與某些複雜性疾病相關，但也代表著個體間良性的多型性變異。然而，亞洲族群基因組劑量變異的訊息仍然有限，我們使用CMDX Bac Array CA2500/ CA3000來鑑別台灣族群1015個個體其CNV的分布，總計發現了438個發生CNV訊號的位置，其中有6個區域其CNV的發生率超過20%，而大多數CNV(92.44%)的變異範圍小於1 Mb，平均每個個體發生CNV的次數為4.36次。發生CNV的區域中，有54.79%和片段性重複序列的位置重疊；64.49%覆蓋基因；92.47%已在相關的文獻報告過，只有7.53%是首次在此篇研究中發現。和先前的文獻相較，Bac Array所偵測的CNVs比高解析度的平台要少的多，但正因為如此，可以降低臨床病理診斷的干擾，因此此篇文獻所使用的Bac Array較適合用於產前、臨床診斷。此篇研究建立屬於台灣族群的CNV圖譜，補足CNV資料庫的族群變異性，可供作臨床遺傳諮詢的參考。

Copy number variation is a source of genetic diversity in humans. CNVs can cause Mendelian or sporadic traits, be associated with complex disease, also represent benign polymorphic variants between individuals. However, CNVs information of Asian populations remains unexplored. We identified CNV distribution of 1015 individuals in Taiwan populations by using CMDX Bac Array CA2500/ CA3000 and find 438 loci with CNV signals. The CNV frequencies of six regions are over 20%. Most CNVs (92.44%) size are shorter than 1 Mb. Average CNV number in each individual is 4.36. Among CNV regions, 54.79% regions overlap with segmental duplication, 64.49% regions cover gene, 92.47% regions are reported in previous study, only 7.53% regions are novel in this study. In contrast to previous studies, CNVs identified are much less than the platform with high resolution. But it lower disturbance in clinical pathologic diagnosis for this reason. So, Bac array used in this study is more appropriate for prenatal, clinical diagnosis. This study establish CNV map of Taiwan populations for further reference of genetic consulting.