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 () and
Liang Wang ()
Additional contact information
Peng Zhang: The First Affiliated Hospital of Zhengzhou University
Ji-Han Xia: University of Oulu
Jing Zhu: Medical College of Wisconsin
Ping Gao: University of Oulu
Yi-Jun Tian: Medical College of Wisconsin
Meijun Du: Medical College of Wisconsin
Yong-Chen Guo: Medical College of Wisconsin
Sufyan Suleman: University of Oulu
Qin Zhang: University of Oulu
Manish Kohli: Mayo Clinic
Lori S. Tillmans: Mayo Clinic, 200 First Street SW
Stephen N. Thibodeau: Mayo Clinic, 200 First Street SW
Amy J. French: Mayo Clinic, 200 First Street SW
James R. Cerhan: Mayo Clinic
Li-Dong Wang: The First Affiliated Hospital of Zhengzhou University
Gong-Hong Wei: University of Oulu
Liang Wang: Medical College of Wisconsin
Nature Communications, 2018, vol. 9, issue 1, 1-12
Abstract:
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.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04451-x
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DOI: 10.1038/s41467-018-04451-x
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