臺灣博碩士論文加值系統

目標：
利用全基因譜(Genome-Wide)之SNPs(Single nucleotide polymorphisms)資料的品質，探討父母基因型的非隨機訊息遺失(informative missingness)區域。

方法：
利用HapMap(The International HapMap Project)的基因型、質量分數、和家庭結構的資料，分別以分數低於10000、9000、8000和7000的基因型當作遺失值，得到四個不同基因型遺失的資料，然後藉由郭炤裕教授提出檢測父母基因型為訊息缺失的新方法─TIMBD，找出四個不同基因型遺失的資料中，TIMBD皆小於0.05的SNPs，共有20個。經由NCBI(The National Center for Biotechnology Information)公司提供的SNPs區域圖，找出這20個SNPs附近相關的SNPs和發表的文章，並且利用Haploview找出SNPs之間連鎖不平衡(Linkage disequilibrium)的相關性。

結果：
20個有RS numbers的SNPs中，只有找到一篇研究肥胖與心血管疾病有關的文章，不過20個SNPs都沒有文章被重複發表，因此這些區域可能是假相關。

Objectives:
This dissertation aims to explore the genome-wide pattern of informative missingness among parent genotypes due to various qualities of genotyping.

Methods:
Genotype, quality score, and pedigree of HapMap data were merged together and genotype scores below 10000, 9000, 8000, and 7000 were assigned to be missing values. Therefore, four sets of trio data with partial missing parental genotypes were implemented by the TIMBD (Guo, 2012), which determines whether parental genotypes are missing informatively or not. SNPs that are significant in the four sets of trio data were studied and 20 of them were matched with RS numbers. Using the NCBI (The National Center for Biotechnology Information) data base, the SNP regional map was used to identify published associations and nearby SNPs in LD with the 20 SNPs. Haploview was used to find linkage disequilibrium information between the 20 SNPs and nearby SNPs.

Results:
Among the 20 SNPs where parental genotypes are missing informatively due to various genotyping qualities, only one SNP was reported to be associated with obesity and cardiovascular disease. No replications were reported by the 20 SNPs. It is likely that these significant SNPs are false positives.

目錄
誌謝 i
中文摘要 ii
英文摘要 iii
目錄 iv
圖目錄 v
表目錄 vi
第一章 緒論 1
第一節 研究背景 1
第二節 研究目的 4
第二章 文獻探討 5
第一節 訊息缺失文獻探討 5
第二節 統計方法文獻探討 9
第三章 研究方法 15
第一節 研究資料 15
第二節 資料的整理與合併 17
第三節 TIMBD方法的應用 18
第四章 研究結果 19
第一節 四個遺失資料顯著的SNPS 19
第二節 NCBI公司SNP區域圖的應用 22
第三節 Haploview的應用 33
第五章 研究結論與建議 44
參考文獻 46
附錄 48
SAS程式碼 87

圖目錄
圖1 rs36051446染色體的區域資訊 22
圖2 rs268442染色體的區域資訊 23
圖3 rs34962711染色體的區域資訊 23
圖4 rs10491858染色體的區域資訊 24
圖5 rs4904408染色體的區域資訊 25
圖6 rs2270511染色體的區域資訊 25
圖7 rs2270822染色體的區域資訊 26
圖8 rs7593染色體的區域資訊 26
圖9 rs28481407染色體的區域資訊 27
圖10 rs609821染色體的區域資訊 27
圖11 rs12331染色體的區域資訊 28
圖12 rs17576874染色體的區域資訊 28
圖13 rs3750800染色體的區域資訊 29
圖14 rs6795271染色體的區域資訊 30
圖15 rs9941507染色體的區域資訊 30
圖16 rs41450848染色體的區域資訊 31
圖17 rs15098168染色體的區域資訊 32
圖18 rs6794999染色體的區域資訊 32
圖19 rs1060060染色體的區域資訊 32
圖20 rs2132135染色體的區域資訊 33
圖21 rs36051446利用Haploview 4.2的資訊 34

表目錄
表1 有染病小孩三種三元體類型(triads、dyads和monads)的條件分佈 10
表2 關於TIMBD的HRR和EM-HRR統計量 13
表3 家族譜一部分的資料 16
表4 基因型一部分的資料 17
表5 質量分數一部分的資料 17
表6 比較四個不同基因型遺失資料後共同顯著的SNPS 20
表7 42個共同SNPS中20個轉換成RS number 21
表8 第15到19個主要SNPS的NCBI位置資訊和Haploview輸入範圍 40
表9 20個主要SNPS所有的相關資訊 43

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