Alcohol and Alcoholism Advance Access originally published online on May 12, 2008
Alcohol and Alcoholism 2008 43(5):505-515; doi:10.1093/alcalc/agn032
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Published by Oxford University Press on behalf of Medical Council on Alcohol 2008
Addictions Biology: Haplotype-Based Analysis for 130 Candidate Genes on a Single Array
1 Laboratory of Neurogenetics, DICBR, NIAAA, 5625 Fishers Lane, Rockville, MD 20852, USA
2 Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
3 Departments of Human Genetics, and Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
4 Department of Molecular and Experimental Medicine and Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA
5 Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine, New Haven, CT, USA
6 Department of Psychiatry, Columbia University, NY, USA
7 Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
8 Department of Veterans Affairs, Psychiatry Service, New Jersey Health System, East Orange, NJ, USA
9 Department of Pharmacology, University of Colorado at Denver and Health Science Center, Aurora, CO, USA
* Corresponding author: Laboratory of Neurogenetics, NIAAA, 5625 Fishers Lane, Room 3S32 MSC9412, Rockville, MD 20852-1728, USA. 301-437633; Tel: +1-301-326-7293; Fax: +1-301-480-2839; E-mail: chodg{at}mail.nih.gov
Received 7 November 2007; first review notified 12 February 2008; in revised form 13 March 2008; accepted 2 April 2008; advance access publication 12 May 2008
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Abstract |
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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.
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