Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness

• 作者: Norman E Buroker
• 来源期刊: 世界血液学杂志
• 学科: 医学
• 关键词: REGULATORY single nucleotide polymorphisms Alleles TRANSCRIPTIONAL factors TRANSCRIPTIONAL factor binding sites Linkage disequilibrium DISEASE or SICKNESS
• 年，卷（期）: 2016,（4）
• 页码范围: 75-87
• 页数: 13页
• 分类号: R

摘要

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.