The Cancer Genome Anatomy Project's Genetic Annotation Initiative

癌症基因组解剖计划(CGAP)遗传注释倡议(GAI)是一项努力，旨在扩大可用于癌症研究的基于基因的遗传分析试剂的集合。其目标是提高通过NCI的CGAP产生的信息和资源在家庭和人口遗传研究中的效用。对人类基因组的高分辨率遗传分析有望提供对常见疾病易感性的重要洞察。要进行这种分析，需要收集高通量、高密度的分析试剂。使用一套序列分析工具(SNP管道)，我们通过检查公开可用的表达序列标签(EST)色谱图，在1999年11月11-11月发布的Unigene版本(#102)包含的序列中鉴定了12832个高概率的“候选”SNP。已经开发了聚合酶链式反应分析来验证这些数据的子集。以92名CEPH个体为样本，用MALDI-TOF质谱仪检测了6404个基因座，验证了3646个候选SNPs。这些变异体分布在2987个Unigene簇中，其中1124个是已知基因。总共有256个SNP出现在编码区，其中118个被预测会导致氨基酸替换。现在正在通过检查CEPH家系中的传播来确认成功验证的变异。当确认后，SNP被定位到与合作人类连锁中心(CHLC)参考图谱相关的遗传图谱上。上述方法也已应用于小鼠EST数据。利用这些数据，我们已经确定了3284个候选小鼠SNP，以对人类遗传学社区有用的形式呈现遗传变异，我们基于CHLC/ABI Prism连锁标记集构建了一个完整的遗传/物理SNP图谱。参考标记的遗传图谱位置来自CHLC；物理图谱位置来自GeneMap‘98 GeneBridge 4辐射杂交图谱。超过6,500个候选多态已被放置在一个整合的遗传/物理图谱上。该整合图谱、在EST组装环境中查看候选SNP的基于JAVA的工具和SNP搜索引擎可在我们的网站上找到：http://cgap.nci.nih.gov/GAI.我们为非商业用途提供对我们的SNP检测软件的访问。

The Cancer Genome Anatomies Projects (CGAP) Genetic Annotation Initiative (GAI) is an effort to expand the collection of available gene-based genetic analysis reagents for cancer research. Its goal is to enhance the utility of information and resources generated through the NCI's CGAP in genetic studies of families and populations. High resolution genetic analysis of the human genome promises to provide important insight into common disease susceptibility. To perform such analysis will require a collection of high-throughput, high-density analysis reagents. Using a set of sequence analysis tools, (the SNP pipeline) we have identified 12832 high-probability "candidate" SNPs among sequences contained in the 11- November 1999 UniGene release (#102) by examining publicly available expressed sequence tag (EST) chromatograms. PCR assays have been developed to validate a subset of these data. Using a pooled sample of 92 independent CEPH individuals, 6404 loci were examined by MALDI-TOF mass spectrometry and 3646 candidate SNPs validated. These variants are distributed among 2987 Unigene clusters of which 1124 are known genes. A total of 256 of the SNPs occur in coding regions and 118 are predicted to result in an amino acid substitution. Successfully validated variants are now being confirmed by examining transmission in CEPH pedigrees. When confirmed, the SNP is genetically mapped relative to the Cooperative Human Linkage Center (CHLC) reference maps. The above approach has also been applied to mouse EST data. Using this data 3284 candidate mouse SNPs have been identified To present the genetic variants in a format useful for the human genetics community we have constructed an integrated genetic/physical SNP map based on the CHLC/ABI Prism linkage marker set. Genetic map positions of reference markers are from the CHLC; physical map positions are from the GeneMap'98 Genebridge4 radiation hybrid map. More than 6500 of the candidate polymorphisms have been placed on an integrated genetic/physical map The integrated map, a Java-based tool for viewing candidate SNPs in the context of EST assemblies and a SNP search engine are available at our website: http://cgap.nci.nih.gov/GAI. We provide access to our SNP detection software for non-commercial use.