A sequential methodology for the rapid identification and characterization of breast cancer-associated functional SNPs
| العنوان: | A sequential methodology for the rapid identification and characterization of breast cancer-associated functional SNPs |
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| المؤلفون: | Di Wu, Toren Finkel, Wei Sun, Ting Wu, Jing Cui, Danli Jiang, Xiaoyu Zhang, Gang Li, Jean J. Zhao, Yihan Zhao, Steffi Oesterreich, Min Qian |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Linkage disequilibrium, Sequence analysis, Science, Blotting, Western, MAP Kinase Kinase Kinase 1, General Physics and Astronomy, Breast Neoplasms, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, MAP3K1, Computational biology, Regulatory Sequences, Nucleic Acid, Biology, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Mass Spectrometry, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Cell Line, Tumor, Humans, Genetic Predisposition to Disease, Receptor, Fibroblast Growth Factor, Type 2, lcsh:Science, Genetic association study, Adaptor Proteins, Signal Transducing, Regulation of gene expression, Multidisciplinary, Sequence Analysis, DNA, General Chemistry, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Regulatory sequence, 030220 oncology & carcinogenesis, MCF-7 Cells, Female, lcsh:Q, Genome-Wide Association Study |
| الوصف: | GWAS cannot identify functional SNPs (fSNP) from disease-associated SNPs in linkage disequilibrium (LD). Here, we report developing three sequential methodologies including Reel-seq (Regulatory element-sequencing) to identify fSNPs in a high-throughput fashion, SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify fSNP-bound proteins and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to detect allele-specific protein:fSNP binding. We first apply Reel-seq to screen a library containing 4316 breast cancer-associated SNPs and identify 521 candidate fSNPs. As proof of principle, we verify candidate fSNPs on three well-characterized loci: FGFR2, MAP3K1 and BABAM1. Next, using SDCP-MS and AIDP-Wb, we rapidly identify multiple regulatory factors that specifically bind in an allele-imbalanced manner to the fSNPs on the FGFR2 locus. We finally demonstrate that the factors identified by SDCP-MS can regulate risk gene expression. These data suggest that the sequential application of Reel-seq, SDCP-MS, and AIDP-Wb can greatly help to translate large sets of GWAS data into biologically relevant information. It is often difficult to identify functional SNPs from disease-associated SNPs in linkage disequilibrium. Here, the authors present Reel-seq, SDCP-MS and AIDP-Wb, three sequential methodologies for fSNP identification and characterization. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1cc4aa7623a140183dd84a3bb346bf26 https://doaj.org/article/7e2afe32d69f4fc0b8f9d3871c094446 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1cc4aa7623a140183dd84a3bb346bf26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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