University of Oulu

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

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

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Author: Zhang, Peng1; Xia, Ji-Han2; Zhu, Jing3;
Organizations: 1Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
2Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu
3Department of Pathology, MCW Cancer Center, Medical College of Wisconsin
4Department of Oncology, Mayo Clinic
5Department of Laboratory Medicine and Pathology, Mayo Clinic
6Department of Health Sciences Research, Mayo Clinic
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2018
Publish Date: 2018-08-14


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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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 9
Issue: 1
Article number: 2022
DOI: 10.1038/s41467-018-04451-x
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This study was supported by the National Institutes of Health (R01 CA157881) and the Advancing a Healthier Wisconsin (Project# 5520227) awarded to L.W., the Academy of Finland (284618 and 279760) and University of Oulu Strategic Funds and Jane & Aatos Erkko Foundation awarded to G.-H.W., the National High-Tech Research and Development Program of China (SQ2015AA0202183) and the Doctoral Team Foundation of the First Affiliated Hospital of Zhengzhou University (2016-BSTDJJ-03) awarded to L.-D.W., and the China Scholarship Council (No. 201407040025) awarded to P.Z.
Academy of Finland Grant Number: 284618
Detailed Information: 284618 (Academy of Finland Funding decision)
279760 (Academy of Finland Funding decision)
Dataset Reference: Electronic supplementary material
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