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

doi:10.1038/s41467-018-04451-x

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

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21 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 language	English (US)
Article number	2022
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04451-x
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Zhang, P., Xia, J. H., Zhu, J., Gao, P., Tian, Y. J., Du, M., Guo, Y. C., Suleman, S., Zhang, Q., Kohli, M., Tillmans, L. S., Thibodeau, S. N., French, A. J., Cerhan, J. R., Wang, L. D., Wei, G. H., & Wang, L. (2018). High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing. Nature communications, 9(1), Article 2022. https://doi.org/10.1038/s41467-018-04451-x

Zhang, P, Xia, JH, Zhu, J, Gao, P, Tian, YJ, Du, M, Guo, YC, Suleman, S, Zhang, Q, Kohli, M, Tillmans, LS, Thibodeau, SN, French, AJ, Cerhan, JR, Wang, LD, Wei, GH & Wang, L 2018, 'High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing', Nature communications, vol. 9, no. 1, 2022. https://doi.org/10.1038/s41467-018-04451-x

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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.",

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

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AU - Thibodeau, Stephen N.

AU - French, Amy J.

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

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