Target SNP selection in complex disease association studies

BMC Bioinformatics
Matthias Wjst

Abstract

The massive amount of SNP data stored at public internet sites provides unprecedented access to human genetic variation. Selecting target SNP for disease-gene association studies is currently done more or less randomly as decision rules for the selection of functional relevant SNPs are not available. We implemented a computational pipeline that retrieves the genomic sequence of target genes, collects information about sequence variation and selects functional motifs containing SNPs. Motifs being considered are gene promoter, exon-intron structure, AU-rich mRNA elements, transcription factor binding motifs, cryptic and enhancer splice sites together with expression in target tissue. As a case study, 396 genes on chromosome 6p21 in the extended HLA region were selected that contributed nearly 20,000 SNPs. By computer annotation ~2,500 SNPs in functional motifs could be identified. Most of these SNPs are disrupting transcription factor binding sites but only those introducing new sites had a significant depressing effect on SNP allele frequency. Other decision rules concern position within motifs, the validity of SNP database entries, the unique occurrence in the genome and conserved sequence context in other mammalian genomes. On...Continue Reading

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Citations

Dec 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jan WehkampCharles L Bevins
Feb 1, 2008·Journal of the American Society of Nephrology : JASN·Hong LiuJingyu Lu
Sep 4, 2012·International Journal of Molecular Sciences·Xue-Xi YangMing Li
Jun 17, 2011·Journal of Genetics·Benjamin H L TanUNKNOWN European Palliative Care Research Collaborative
Oct 6, 2005·Shock·John ArcaroliEdward Abraham
Jun 17, 2005·Paediatric and Perinatal Epidemiology·Richard JonesDavid Herrick
Jun 24, 2014·Journal of Theoretical Biology·Xiao ChenTao Xu
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Mar 22, 2014·Biomedical Reports·Chengcheng ZhaoHong Fan

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Methods Mentioned

BETA
genotyping
feature array
PCR
chip

Software Mentioned

CELERA
Proscan
Apache
Mozilla Firefox
dbSNP
GeneSNPs
DoTS Database
TRANSFAC
UCSC
Solaris

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