Supplementing high-density SNP microarrays for additional coverage of disease-related genes

Addiction as a paradigm

Scott F. Saccone, Laura J. Bierut, Elissa J. Chesler, Peter W. Kalivas, Caryn Lerman, Nancy L. Saccone, George R. Uhl, Chuan Yun Li, Vivek M. Philip, Howard Edenberg, Stephen T. Sherry, Michael Feolo, Robert K. Moyzis, Joni L. Rutter

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well represented by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions.

Original languageEnglish
Article numbere5225
JournalPLoS One
Volume4
Issue number4
DOIs
StatePublished - Apr 21 2009

Fingerprint

Microarrays
Single Nucleotide Polymorphism
Genes
genes
prioritization
mice
Databases
HapMap Project
linkage disequilibrium
Linkage Disequilibrium
Medical Genetics
genotyping
Human Genome
functional properties
quantitative trait loci
Genetic Promoter Regions
Information Systems
researchers
promoter regions
Conservation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Saccone, S. F., Bierut, L. J., Chesler, E. J., Kalivas, P. W., Lerman, C., Saccone, N. L., ... Rutter, J. L. (2009). Supplementing high-density SNP microarrays for additional coverage of disease-related genes: Addiction as a paradigm. PLoS One, 4(4), [e5225]. https://doi.org/10.1371/journal.pone.0005225

Supplementing high-density SNP microarrays for additional coverage of disease-related genes : Addiction as a paradigm. / Saccone, Scott F.; Bierut, Laura J.; Chesler, Elissa J.; Kalivas, Peter W.; Lerman, Caryn; Saccone, Nancy L.; Uhl, George R.; Li, Chuan Yun; Philip, Vivek M.; Edenberg, Howard; Sherry, Stephen T.; Feolo, Michael; Moyzis, Robert K.; Rutter, Joni L.

In: PLoS One, Vol. 4, No. 4, e5225, 21.04.2009.

Research output: Contribution to journalArticle

Saccone, SF, Bierut, LJ, Chesler, EJ, Kalivas, PW, Lerman, C, Saccone, NL, Uhl, GR, Li, CY, Philip, VM, Edenberg, H, Sherry, ST, Feolo, M, Moyzis, RK & Rutter, JL 2009, 'Supplementing high-density SNP microarrays for additional coverage of disease-related genes: Addiction as a paradigm', PLoS One, vol. 4, no. 4, e5225. https://doi.org/10.1371/journal.pone.0005225
Saccone, Scott F. ; Bierut, Laura J. ; Chesler, Elissa J. ; Kalivas, Peter W. ; Lerman, Caryn ; Saccone, Nancy L. ; Uhl, George R. ; Li, Chuan Yun ; Philip, Vivek M. ; Edenberg, Howard ; Sherry, Stephen T. ; Feolo, Michael ; Moyzis, Robert K. ; Rutter, Joni L. / Supplementing high-density SNP microarrays for additional coverage of disease-related genes : Addiction as a paradigm. In: PLoS One. 2009 ; Vol. 4, No. 4.
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