High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing
Zhang, Peng; Xia, Ji-Han; Zhu, Jing; Gao, Ping; Tian, Yi-Jun; Du, Meijun; Guo, Yong-Chen; Suleman, Sufyan; Zhang, Qin; Kohli, Manish; Tillmans, Lori S.; Thibodeau, Stephen N.; French, Amy J.; Cerhan, James R.; Wang, Li-Dong; Wei, Gong-Hong; Wang, Liang (2018-05-22)
Zhang, P., Xia, J., Zhu, J., Gao, P., Tian, Y., Du, M., Guo, Y., Suleman, S., Zhang, Q., Kohli, M., Tillmans, L., Thibodeau, S., French, A., Cerhan, J., Wang, L., Wei, G., Wang, L. (2018) High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing. Nature Communications, 9 (1), 2022. doi:10.1038/s41467-018-04451-x
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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.
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