Presentation is loading. Please wait.

Presentation is loading. Please wait.

Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array Nan Hu,1 Chaoyu Wang,1 Ying Hu,2 Howard H. Yang,2 Carol Giffen,5 Ze-Zhong.

Similar presentations


Presentation on theme: "Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array Nan Hu,1 Chaoyu Wang,1 Ying Hu,2 Howard H. Yang,2 Carol Giffen,5 Ze-Zhong."— Presentation transcript:

1 Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array Nan Hu,1 Chaoyu Wang,1 Ying Hu,2 Howard H. Yang,2 Carol Giffen,5 Ze-Zhong Tang,6 Xiao-Yu Han,6 Alisa M. Goldstein,4 Michael R. Emmert-Buck,3 Kenneth H. Buetow,2 Philip R. Taylor,1 and Maxwell P. Lee2

2 AbstractAbstract IntroductionIntroduction Materials and MethodsMaterials and Methods Results and DiscussionResults and Discussion

3 Abstract 找 Esophageal squamous cell carcinoma (ESCC) 病患的可能遺 傳基因 。 分別 correct 50 病患 與 50 正常人的 DNA. 分析每個 DNA 中 10,000 SNP 的序列。 比較病患與正常人的這 10,000 SNP --> 找到 37 個特別的 SNPs 37 個特別的 SNPs 與已知的 cancers 相關的基因有關。

4 AbstractAbstract IntroductionIntroduction Materials and MethodsMaterials and Methods Results and DiscussionResults and Discussion

5 Introduction ESCC is one of the most common malignancies in the Chinese (Shanxi Province) 目前已經知道 susceptibility biomarkers involved in ESCC 。但 是 Association studies with 10,000 SNP -> 遺傳基因

6 Esophageal squamous cell carcinoma (ESCC) 鳞状细胞癌:占食管 癌的 90% 以上 发生于食管鳞状上皮 以食管中段为最多, 其次为下段。

7 食道鳞状细胞癌 (ESCC)

8 The foundation of genetics Mendel's laws –1. Law of unit characters Paired alleles control the inheritance of traits Homozygous vs Heterozygous AAAa aa

9 SNP DNA Sequence GATATTCGTACGGA-T GATGTTCGTACTGAAT GATATTCGTACGGA-T GATATTCGTACGGAAT GATGTTCGTACTGAAT SNP AG- 2/6 GTA 3/6 AGA 1/6 Phenotype Black eye Brown eye Black eye Blue eye Brown eye

10 AA Aa aa Cancer (50)Normal (50) Association studies AAAa aa

11 Odds Ratio (OR) Disease Unaffected Risk Factor +p +D p +U -p -D p -U Association studies

12 Examples: Alzheimer’s Alzheimer’s disease and ApoE E4 presentE4 absent Patients5833 Controls1655 The E4 allele appears to be positively associated with Alzheimer’s disease: Odds Ratio = (58/16)/(33/55) = 6 LOD : log odds ratio 有相關

13 Affymetrix (10,000) Each spot may be AA Aa aa

14 AbstractAbstract IntroductionIntroduction Materials and MethodsMaterials and Methods Results and DiscussionResults and Discussion

15 Patients and Controls 人體試驗委員會同意 (IRB) 。 50 patients (males) 25 with a positive family history of ESCC 25 without a family history of ESCC 50 Controls (males) Age-, sex-, and ancestral home for all controls was in Shanxi Province.

16 Biological Specimen Collection and Processing collect Patients and Control 血液檢體 (10 mL) 。 血液檢體 --> extract Genomic DNA 。 Affymetrix 10K Chip analysis with 500 ng DNA 。 統計分析 (Association studies)

17 GeneChip Mapping 10K Array major benefits 1.Requires only 250 ng of genomic DNA per sample 2.Easy-to-use (within 2 days) 3.Get 10,000 SNPs genotyping

18 Affymetrix GA2500 Genechip System

19

20

21

22 GeneChip ® Mapping Assay Overview(2)

23 Patients and Controls Information ‘‘ Signal Detection Rate ’’ is the percentage of SNPs that pass the discrimination filter. ‘‘ Call Rate ’’ is the percentage of SNPs called on the array. 榨菜 11560

24 Principal Components Analysis (PCA) 10k array Patients controls 找出最符合的 SNP ( n = 37) (n = 3000) 確認資料的形態 同時表現資料中的相同和差異 容易歸納資料

25 AbstractAbstract IntroductionIntroduction Materials and MethodsMaterials and Methods Results and DiscussionResults and Discussion

26 找出最符合的 SNP ( n = 37) RandomSNP ( n = 3000) Figure 1. PCA analysis of cases and controls using multiloci genotypes. We used A allele as the recessive allele for genotype coding (AA, AB, BB) =(1, 0, 0). E, cases (red); N, controls (green). Details of the PCA can be found in Materials and Methods. A, X axis and Y axis, first and second principal components of PCA analysis using 37 SNPs from the 10K chip genotypes of 50 cases and 50 controls. B, X axis and Y axis, first and second principal components of PCA analysis using 3,369 SNPs (all SNPs with no missing genotype data) from the 10K chip genotypes of 50 cases and 50 controls.

27 The foundation of genetics Mendel's laws (cont.) –2. Law of dominance (cont.) Dominant, 顯性 (AA, Aa) vs Recessive, 隱性 (aa) 碗豆的特徵因素 種子:平滑圓形 ( 顯性 ) 或皺紋 種子內部顏色:黃色 ( 顯性 ) 或綠色 未成熟豆夾的顏色:綠色 ( 顯性 ) 或黃色 成熟豆夾的形態:膨脹 ( 顯性 ) 或壓縮 花的顏色:紫色 ( 顯性 ) 或白色。 花的位置:枝腋 ( 顯性 ) 或枝頂。 莖的長度:短 (9-18 英吋 ) 或長 (6-7 英呎 )( 顯性 )

28 AA Aa aa Cancer (50)Normal (50) AA Aa+aa Cancer (50)Normal (50) Association studies

29 Dominant, 顯性 (AA, Aa) vs Recessive, 隱性 (aa)

30 Continuous AAAaaa 50%25%5% Recessive Dominant AA+Aa aa 50%5% AA Aa + aa 50%5%

31

32 Questions?


Download ppt "Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array Nan Hu,1 Chaoyu Wang,1 Ying Hu,2 Howard H. Yang,2 Carol Giffen,5 Ze-Zhong."

Similar presentations


Ads by Google