Published online Nov 6, 2016. doi: 10.5315/wjh.v5.i4.75
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
To identify punitive transcriptional factor binding sites (TFBS) from regulatory single nucleotide polymorphisms (rSNPs) that are significantly associated with disease.
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.
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.
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.
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.