中心館藏網址 http://tulips.ntu.edu.tw/record=b2172362*cht

[ 摘要 ]
本篇論文利用單一核苷酸多型性(SNP)分布之差異針對痛風及肝癌作遺傳學研究。肝癌在台灣是癌症十大死因第一位，痛風盛行率在台灣泰雅族為全世界最高(11.7%)。在肝癌方面，前人研究顯示利用微衛星標記發現在人類染色體4q12-23有對偶基因缺失的情況。利用比較基因體雜交法，發現肝癌病人在一些染色體臂有染色體不正常缺失的情況，48%的病人在人類染色體4q21-24區域都有染色體缺失的情況。顯示肝癌抑癌基因可能座落在此區域。在痛風方面，對台灣原住民作全基因掃描發現在人類染色體4q25有一個與痛風高度連鎖的微衛星標記D4S2623，lod score高達4.3。以上原因為本論文針對人類染色體4q23-25進行遺傳研究之動機。
另外，為了整合染色體4q22-25計畫，我建立一個整合計畫之網頁，網頁包括遺傳研究所需之SNP基因定型(genotyping)資料庫。此資料庫收集台灣漢族及原住民之SNP基因定型資料，存放與痛風、肝癌相關之SNP與在漢族和泰雅族顯著分佈差異之SNP。另外從公共資料庫收集痛風候選基因之SNP而建立一個痛風SNP資料庫。
為了發現與痛風和肝癌相關之SNP，本論文分別利用ABI及Beckman兩套之系統做基因定型分析，然後利用卡方檢定分析在不同分組間有顯著差異之SNP，並且比較此兩套系統的差異。

[ 英文摘要 ]
The thesis is aiming at genomic studies of gout and Hepatocellular carcinoma (HCC) in Taiwan by analyzing the single nucleotide polymorphism (SNP) distribution between normal controls and patients. The prevalence of gout in Taiwan‘s Atayal aborigines is the highest in the world. Hepatocellular carcinoma (HCC) is highly prevalent in Asia and Africa and also is the highly-incident cancer in Taiwan. In human hepatocellular carcinoma (HCC), microsatellite polymorphism analysis has been demonstrated frequent (77%) allelic loss on chromosomes 4q within the common region mapped to chromosome 4q12-23. By using comparative genomic hybridization (CGH), loss abnormalities were frequently detected on some chromosome arms. One of the minimal overlapping regions is at human chromosome 4q21-24, suggesting that there may be a HCC suppressor gene located in this region. On the other hand, genome-wide scan for gout in Taiwanese aborigines has shown that there is a highly significant linkage (LOD=4.3) between gout and microsatellite marker D4S2623 on chromosome 4q25. These evidences motivated us to further conduct genomic studies on Human chromosome 4q23-25.
To integrate several chromosome 4q22-25 projects, I established a chromosome 4q22-25 project-integrated website and created a SNP genotyping database for genomic studies in the integrated-website. The database includes SNP information of Han Chinese and aborigines in Taiwan, not only to identify SNPs associated with gout and HCC, but also to identify SNPs with significant difference between Han Chinese and aborigines. Furthermore, I created a gout database collecting publicly-available SNPs in gout candidate genes.
To discover SNPs of candidate genes associated with gout or HCC, I have taken a two-step approach. The first step is to conduct genotyping by two different systems and the second step is to analyze significant different SNPs between different groups by Chi-square tests. I also compared differences between two genotyping systems, ABI and Beckman.