Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hematol. Nov 6, 2016; 5(4): 75-87
Published online Nov 6, 2016. doi: 10.5315/wjh.v5.i4.75
Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness
Norman E Buroker
Norman E Buroker, Department of Pediatrics, University of Washington, Seattle, WA 98195, United States
Author contributions: Buroker NE analyzed all the data and wrote the manuscript.
Institutional review board statement: The manuscript did not use human or animal subjects.
Informed consent statement: The manuscript did not use human or animal subjects.
Conflict-of-interest statement: To the best of my knowledge, no conflict of interest exists.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Norman E Buroker, PhD, Department of Pediatrics, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, United States. nburoker@u.washington.edu
Telephone: +1-206-6160472 Fax: +1-206-6160471
Received: May 8, 2016
Peer-review started: May 9, 2016
First decision: June 13, 2016
Revised: June 24, 2016
Accepted: August 11, 2016
Article in press: August 13, 2016
Published online: November 6, 2016
Processing time: 180 Days and 23.8 Hours
Abstract
AIM

To identify punitive transcriptional factor binding sites (TFBS) from regulatory single nucleotide polymorphisms (rSNPs) that are significantly associated with disease.

METHODS

The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor (TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rSNPs. Computational tools can be used to identify unique punitive TFBS created by rSNPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rSNPs.

RESULTS

rSNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles compared to 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.

CONCLUSION

From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.

Keywords: Regulatory single nucleotide polymorphisms; Alleles; Transcriptional factors; Transcriptional factor binding sites; Linkage disequilibrium; Disease or sickness

Core tip: Disease or trait-predisposing single nucleotide polymorphisms (SNPs) in or near genes can alter the transcriptional factor binding sites (TFBS) for the TFs regulating the gene; thereby affecting the health of an individual. In this report, the disease or sickness associated regulatory SNPs (rSNPs) within a sampling of nine human genes were studied with respect to the alterations in TFBS. From this sampling there were 73 punitive unique TFBS generated by the common rSNP alleles compared to 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of affecting the health of person.