Hodgkinson Colin A, Yuan Qiaoping, Xu Ke, Shen Pei-Hong, Heinz Elizabeth, Lobos Elizabeth A, Binder Elizabeth B, Cubells Joe, Ehlers Cindy L, Gelernter Joel, Mann John, Riley Brien, Roy Alec, Tabakoff Boris, Todd Richard D, Zhou Zhifeng, Goldman David
Laboratory of Neurogenetics, NIAAA, 5625 Fishers Lane, Room 3S32 MSC9412, Rockville, MD 20852-1728, USA.
Alcohol Alcohol. 2008 Sep-Oct;43(5):505-15. doi: 10.1093/alcalc/agn032. Epub 2008 May 12.
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.
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.
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.
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.
开发一组能够提取酗酒、其他成瘾以及情绪和焦虑障碍相关候选基因完整单倍型信息的标记物。
使用Illumina GoldenGate SNP基因分型技术,在7个病例/对照群体和51个参考群体中对总共130个基因进行单倍型标签和基因分型,确定单倍型覆盖率。我们还构建并确定了一组186个祖先信息标记物的效能。
平均对1465个位点进行了基因分型,平均完成率为91.3%,平均检出率为98.3%,重复率为99.7%。两个数据集的表现降低了完成率和检出率,突出了DNA质量在高通量检测中的重要性。对成瘾阵列标记的单核苷酸多态性(SNPs)与Illumina和Affymetrix市售全基因组阵列捕获的单倍型进行比较,结果表明,在所有可获得数据的群体中,标签SNPs与最佳全基因组阵列的性能相当。
诸如这种以成瘾为重点的阵列等单倍型标签候选基因阵列,是一种具有成本效益的方法,可生成高质量的SNP基因分型数据,有助于对诸如酒精和成瘾研究人员感兴趣的这130个基因等基因面板进行基于单倍型的分析。纳入186个祖先信息标记物可检测和校正混杂情况,并进一步提高阵列的实用性。