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- Title
High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing.
- Authors
Peng Zhang; Ji-Han Xia; Jing Zhu; Ping Gao; Yi-Jun Tian; Meijun Du; Yong-Chen Guo; Suleman, Sufyan; Qin Zhang; Kohli, Manish; Tillmans, Lori S.; Thibodeau, Stephen N.; French, Amy J.; Cerhan, James R.; Li-Dong Wang; Gong-Hong Wei; Liang Wang
- Abstract
Functional characterization of disease-causing variants at risk loci has been a significant challenge. Here we report a high-throughput single-nucleotide polymorphisms sequencing (SNPs-seq) technology to simultaneously screen hundreds to thousands of SNPs for their allele-dependent protein-binding differences. This technology takes advantage of higher retention rate of protein-bound DNA oligos in protein purification column to quantitatively sequence these SNP-containing oligos. We apply this technology to test prostate cancer-risk loci and observe differential allelic protein binding in a significant number of selected SNPs. We also test a unique application of self-transcribing active regulatory region sequencing (STARR-seq) in characterizing allele-dependent transcriptional regulation and provide detailed functional analysis at two risk loci (RGS17 and ASCL2). Together, we introduce a powerful high-throughput pipeline for large-scale screening of functional SNPs at disease risk loci.
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04451-x