Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework  

作　　者：ZHANG RuiJie1, LI Xia1,2, JIANG YongShuai1, LIU GuiYou1, LI ChuanXing1, ZHANG Fan1, XIAO Yun1 & GONG BinSheng1 1 Department of Bioinformatics, Harbin Medical University, Harbin 150086, China 2 Biomedical Engineering Institute of CUMS, Beijing 100054, China 

出　　处：《Science China(Life Sciences)》2009年第2期163-172,共10页中国科学（生命科学英文版）

基　　金：Supported by the National Natural Science Foundation of China (Grant Nos. 30570424, 60601010 and 30600367);the National High-Tech Research and Devel-opment Program of China, (Grant No.2007AA02Z329);the Key Science and Tech-nology Program of Heilongjiang Province(Grant No.GB03C602-4);Natural Science Foundation of Heilongjiang Province (Grant No. F2008-02);Youth Science Founda-tion of Harbin Medical University (Grant No. 060045);Science Foundation of Heilongjiang Province Education Department (Grant Nos. 11531113 and 1152hq28).

摘　　要：High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alco- holism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1~22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes pre- cisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with ex- isting knowledge framework.High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alco- holism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1~22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes pre- cisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with ex- isting knowledge framework.

关 键 词：HAPLOTYPE block ALCOHOLISM GENE functional ANNOTATION GENE location LINKAGE disequilibrium 

分 类 号：Q75[生物学—分子生物学]