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Nat Commun. 2018 May 22;9(1):2022. doi: 10.1038/s41467-018-04451-x.

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

Author information

1
Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, 450052, Zhengzhou, Henan, China.
2
Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
3
Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 5 A, 90220, Oulu, Finland.
4
Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
5
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
6
Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
7
Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, 450052, Zhengzhou, Henan, China. ldwang2007@126.com.
8
Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 5 A, 90220, Oulu, Finland. gonghong.wei@oulu.fi.
9
Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. liwang@mcw.edu.

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.

PMID:
29789573
PMCID:
PMC5964124
DOI:
10.1038/s41467-018-04451-x
[Indexed for MEDLINE]
Free PMC Article

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