High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing. Nat Commun 2018 May 22;9(1):2022
Date
05/24/2018Pubmed ID
29789573Pubmed Central ID
PMC5964124DOI
10.1038/s41467-018-04451-xScopus ID
2-s2.0-85047766309 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
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 List
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 LMESH terms used to index this publication - Major topics in bold
AllelesDatasets as Topic
Early Detection of Cancer
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Male
Nuclear Proteins
Polymorphism, Single Nucleotide
Prostate
Prostatic Neoplasms
Protein Binding
Quantitative Trait Loci
Risk
