High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing

Peng Zhang, Ji Han Xia, Jing Zhu, Ping Gao, Yi Jun Tian, Meijun Du, Yong Chen Guo, Sufyan Suleman, Qin Zhang, Manish Kohli, Lori S. Tillmans, Stephen N. Thibodeau, Amy J. French, James R. Cerhan, Li Dong Wang, Gong Hong Wei, Liang Wang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Article number2022
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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