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  Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding

Butter, F., Davison, L., Viturawong, T., Scheibe, M., Vermeulen, M., Todd, J. A., et al. (2012). Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding. PLOS GENETICS, 8(9): e1002982. doi:10.1371/journal.pgen.1002982.

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 Creators:
Butter, Falk1, Author              
Davison, Lucy2, Author
Viturawong, Tar1, Author              
Scheibe, Marion1, Author              
Vermeulen, Michiel2, Author              
Todd, John A.2, Author
Mann, Matthias1, Author              
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              

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Free keywords: T-CELL-RECEPTOR; MASS-SPECTROMETRY; QUANTITATIVE PROTEOMICS; POLYMORPHISM; COMPLEXES; ENHANCER; FAMILY
 Abstract: A causative role for single nucleotide polymorphisms (SNPs) in many genetic disorders has become evident through numerous genome-wide association studies. However, identification of these common causal variants and the molecular mechanisms underlying these associations remains a major challenge. Differential transcription factor binding at a SNP resulting in altered gene expression is one possible mechanism. Here we apply PWAS ("proteome-wide analysis of SNPs"), a methodology based on quantitative mass spectrometry that enables rapid screening of SNPs for differential transcription factor binding, to 12 SNPs that are highly associated with type 1 diabetes at the IL2RA locus, encoding the interleukin-2 receptor CD25. We report differential, allele-specific binding of the transcription factors RUNX1, LEF1, CREB, and TFAP4 to IL2RA SNPs rs12722508*A, rs12722522*C, rs41295061*A, and rs2104286*A and demonstrate the functional influence of RUNX1 at rs12722508 by reporter gene assay. Thus, PWAS may be able to contribute to our understanding of the molecular consequences of human genetic variability underpinning susceptibility to multi-factorial disease.

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Language(s): eng - English
 Dates: 2012-09
 Publication Status: Published online
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: PLOS GENETICS
Source Genre: Journal
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Publ. Info: 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA : PUBLIC LIBRARY SCIENCE
Pages: - Volume / Issue: 8 (9) Sequence Number: e1002982 Start / End Page: - Identifier: ISSN: 1553-7404