Addictions biology: Haplotype-based analysis for 130 candidate genes on a single array
Addictions biology: Haplotype-based analysis for 130 candidate genes on a single array
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DOI：
10.1093/alcalc/agn032
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发表时间：
2008-09-01
影响因子：
2.8
通讯作者：
Goldman, David
中科院分区：
文献类型：
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作者：
Hodgkinson, Colin A.;Yuan, Qiaoping;Goldman, David
目的：开发一组能够提取酒精中毒、其他成瘾以及情绪和焦虑障碍候选基因的完整单倍型信息的标记。方法：采用Illumina GoldenGate SNP基因分型技术，对7个病例/对照群体和51个参考群体的130个基因进行单倍型标记和分型，测定单倍型覆盖率。我们还构建并确定了186个祖先信息标记的功效。结果：平均1465个基因座被分型，平均完成率为91.3%，平均调用率为98.3%，重复率为99.7%。两个数据集的性能降低了完成率和调用率，突出了DNA质量在高通量分析中的重要性。将Addictions Array标记snp捕获的单倍型与Illumina和Affymetrix的市售全基因组阵列进行比较，发现在所有可获得数据的人群中，该标记snp与最佳全基因组阵列具有可比性。结论：单倍型标记的候选基因阵列，如这种以成瘾为重点的阵列，代表了一种具有成本效益的方法，可以产生高质量的SNP基因分型数据，这对于基于单倍型的基因面板分析有用，例如酒精和成瘾研究人员感兴趣的130个基因。186个祖先信息标记的包含允许检测和校正混合物，并进一步提高了阵列的实用性。
Aims: To develop a panel of markers able to extract full haplotype information for candidate genes in alcoholism, other addictions and disorders of mood and anxiety. Methods: A total of 130 genes were haplotype tagged and genotyped in 7 case/control populations and 51 reference populations using Illumina GoldenGate SNP genotyping technology, determining haplotype coverage. We also constructed and determined the efficacy of a panel of 186 ancestry informative markers. Results: An average of 1465 loci were genotyped at an average completion rate of 91.3%, with an average call rate of 98.3% and replication rate of 99.7%. Completion and call rates were lowered by the performance of two datasets, highlighting the importance of the DNA quality in high throughput assays. A comparison of haplotypes captured by the Addictions Array tagging SNPs and commercially available whole-genome arrays from Illumina and Affymetrix shows comparable performance of the tag SNPs to the best whole-genome array in all populations for which data are available. Conclusions: Arrays of haplotype-tagged candidate genes, such as this addictions-focused array, represent a cost-effective approach to generate high-quality SNP genotyping data useful for the haplotype-based analysis of panels of genes such as these 130 genes of interest to alcohol and addictions researchers. The inclusion of the 186 ancestry informative markers allows for the detection and correction for admixture and further enhances the utility of the array.