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Genes and classes of genes that contain clustered positive SNPs using the principal, preplanned analyses with criteria noted in Table 1.

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These “converge then cluster” genes thus each contain three or more SNPs that display nominally significant allele frequency differences between both European-American (EA) and African-American (AA) polysubstance abuser vs control comparisons that cluster within <25kb of each other and lie within the gene's exons or within +/−10 kb 3′ or 5′ flanking sequences. Genes are grouped by the class of the function to which they contribute. The numbers of reproducibly positive SNPs that lay in clusters within the gene's exons and in 10 kb genomic flanking regions are noted. Chromosome number and initial chromosomal position for the cluster (bp, NCBI Mapviewer Build 36.1) are listed. “Approach 2/Cluster then converge” genes that were identified by clusters of at least 4 nominally positive SNPs that lay within 10kb of each other and lay within the gene for each sample are listed in the column labeled “2: cluster then converge”. Asterisk identifies genes also identified in [16]. P values are based on 10,000 Monte Carlo simulation trials in which the number of times randomly-selected segments of the genome that lie within genes are assessed for the same features displayed by the actual gene identified. Relevant rs numbers for SNPs are listed in Table S2. dbGAP support lists the numbers of SNPs in the same genes that display nominally-significant differences between cocaine-dependent and nondependent control AA and EA samples from 1M SNP Illumina individual genotyping of samples from COGA, FSCD and COGEND samples as described in dbGAP (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gap).

此类“先聚合后聚类”的基因,均包含3个及以上单核苷酸多态性(Single Nucleotide Polymorphism, SNP)。在欧裔美国人(European-American, EA)与非裔美国人(African-American, AA)的多药物滥用者与对照组的比较分析中,这些SNP均表现出名义上显著的等位基因频率差异,且彼此间的聚类区间小于25kb,同时位于基因的外显子区域,或基因3′、5′侧翼±10kb的序列范围内。研究按基因所参与的功能类别对其进行分组,统计了位于基因外显子及10kb基因组侧翼区域内的可重复阳性SNP数量,并列出了该聚类所在的染色体编号及初始染色体位置(单位:bp,参考美国国家生物技术信息中心图谱查看器(NCBI Mapviewer)构建版本36.1)。在标注为“2:先聚类后聚合”的列中,列出了经如下方式鉴定的“先聚类后聚合”类基因:针对每个样本,至少存在4个名义阳性SNP形成聚类,且这些SNP彼此间距不超过10kb,并均位于该基因内部。带有星号的基因同时在文献[16]中被鉴定到。P值基于10000次蒙特卡洛模拟试验计算得到,该试验用于评估随机选取的基因内基因组片段出现与实际鉴定基因相同特征的次数。相关SNP的rs编号详见表S2。dbGAP(数据库之基因型与表型,database of Genotypes and Phenotypes)支持数据集列出了同一基因中存在的SNP数量,这些SNP在可卡因依赖者与非依赖对照组的非裔美国人、欧裔美国人样本中表现出名义上显著的差异。该数据来自针对COGA、FSCD及COGEND样本开展的基于1M SNP因美纳(Illumina)平台的个体基因分型检测,具体信息详见dbGAP数据库(http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gap)。
创建时间:
2010-01-21
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