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

Author

Listed:
  • Peng Zhang

    (The First Affiliated Hospital of Zhengzhou University
    Medical College of Wisconsin)

  • 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)

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.

Suggested Citation

  • 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., 2018. "High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04451-x
    DOI: 10.1038/s41467-018-04451-x
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    Cited by:

    1. Nikolaos Giannareas & Qin Zhang & Xiayun Yang & Rong Na & Yijun Tian & Yuehong Yang & Xiaohao Ruan & Da Huang & Xiaoqun Yang & Chaofu Wang & Peng Zhang & Aki Manninen & Liang Wang & Gong-Hong Wei, 2022. "Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Jeroen Kneppers & Tesa M. Severson & Joseph C. Siefert & Pieter Schol & Stacey E. P. Joosten & Ivan Pak Lok Yu & Chia-Chi Flora Huang & Tunç Morova & Umut Berkay Altıntaş & Claudia Giambartolomei & Ji, 2022. "Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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