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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: | http://urn.fi/urn:nbn:fi-fe2018081433653 |
| Language: | English |
| Published: |
Springer Nature,
2018
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| Publish Date: | 2018-08-14 |
| Description: |
AbstractFunctional 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. see all
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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 |
| OADOI: | https://oadoi.org/10.1038/s41467-018-04451-x |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3111 Biomedicine |
| Subjects: | |
| 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 279760 |
| Detailed Information: |
284618 (Academy of Finland Funding decision) 279760 (Academy of Finland Funding decision) |
| Dataset Reference: |
Electronic supplementary material |
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https://www.nature.com/articles/s41467-018-04451-x#Sec34 |
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| Copyright information: |
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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https://creativecommons.org/licenses/by/4.0/ |