Characterisation of non-coding genetic variation in histamine receptors using AnNCR-SNP.

Abstract

Almost 90 % of disease-associated genetic variants found using genome wide association studies (GWAS) are located in non-coding regions of the genome. Such variants can affect phenotype by altering important regulatory elements such as promoters, enhancers or repressors, leading to changes in gene expression and consequently disease, such as thyroid cancer and allergic diseases. A number of allergy and atopy related diseases such as asthma and atopic dermatitis are related to histamine receptors; however, these diseases are not fully characterized at the molecular level. Moreover, candidate gene based studies of common variants known as single nucleotide polymorphism (SNPs) located in the coding regions of these receptors have given mixed results. It is important to complement these approaches by identifying and characterising non-coding variants in order to further elucidate the role of these receptors in disease. Here we present an analysis of histamine receptor genes using the tool AnNCR-SNP to characterise variants in non-coding genomic regions. AnNCR-SNP combines bioinformatics and experimental data sets from various sources to predict the effects of genetic variation on gene expression regulation. We find many SNPs located in areas of open chromatin, overlapping with transcription factor binding sites and associated with changes in gene expression in expression quantitative trait loci (eQTL) experiments. Here we present the results as a catalogue of non-coding variation in histamine receptor genes to aid histamine researchers in identifying putative functional SNPs found in GWAS for further validation, and to help select variants for candidate gene studies.