Y play critical role in disease progression and severity. Keywords: MicroRNA
Y play critical role in disease progression and severity. Keywords: MicroRNA, Expression QTL, Epistasis, Autoimmune skin blistering disease, Co-expression analysisBackground The discovery of microRNAs (miRNAs), a class of small endogenous non-coding molecules ranging from 18?4 nt brought a new level of complexity for understanding the mechanisms that constitute various biological processes [1, 2]. The involvement of miRNAs in the control of gene expression has been thoroughly defined for the cell cycle,* Correspondence: [email protected] 1 L eck Institute of Experimental Dermatology, University of L eck, L eck, Germany Full list of author information is available at the end of the articlemetabolism, and immune system and in cancer [3?]. Binding to the 3 or 5 UTR region of genes, miRNAs may yield increased or decreased gene expression levels and have been described to affect various molecular pathways [7]. Approximately half the miRNAs are intergenic with few also located in intronic regions [8, 9]. These are understood to have their own enhancers and promoters and are transcribed by RNA polymerase II [10]. However, it remains unclear whether these are produced as?2016 Gupta et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28914615 Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Gupta et al. BMC Genomics (2016) 17:Page 2 ofby-products of protein-coding gene transcription or whether their biogenesis has its own machinery [11]. Recent studies in murine and human fibroblasts of liver tissues revealed that miRNA expression can either be regulated by their transcriptional genomic location or by other regions in the genome [12]. PD98059 mechanism of action Furthermore, mutations in genes involved in miRNA processing, such as AGO1, DGCR8, and DICER, can cause significant changes in the expression of miRNAs, resulting in altered disease susceptibility [13]. Regarding the skin, in vivo studies show that miRNA biogenesis is dependent on both DICER and DGCR8. A lack of these enzymes causes severe phenotypes [14], underscoring the importance of miRNAs in the regulation of morphogenesis and homeostasis of the skin [15]. Differentially expressed miRNAs are associated with different physiological and pathological processes in the skin such as melanoma, S ary syndrome, psoriasis and atopic dermatitis [16?9]. Advancements have been achieved in understanding various processes regulated by miRNAs. On the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28461585 other hand, the mechanisms that regulate their own expression have so far remained unknown. One possible approach towards understanding their regulation is constraining on genetic loci whose variations statistically link the variable phenotypic effect. We thus performed an in silico expression QTL-based analysis, which has been widely used for deciphering genetic loci regulating gene expression in various biological processes [20]. Su et al. have further shown that expression QTL-based analysis can provide insights into miRNA regulation [12]. However, no study has yet been performed to determine the im.