Genome-Wide CpG Island Methylation Profiles of Cutaneous Skin with and without HPV Infection
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: AL-Eitan, Laith N.; Alghamdi, Mansour A.; Tarkhan, Amneh H.; Al-Qarqaz, Firas A.
Abstract
HPV infection is one of the most commonly transmitted diseases among the global population. While it can be asymptomatic, non-genital HPV infection often gives rise to cutaneous warts, which are benign growths arising from the epidermal layer of the skin. This study aimed to produce a global analysis of the ways in which cutaneous wart formation affected the CpG island methylome. The Infinium MethylationEPIC BeadChip microarray was utilized in order to quantitatively interrogate CpG island methylation in genomic DNA extracted from 24 paired wart and normal skin samples. Differential methylation analysis was carried out by means of assigning a combined rank score using RnBeads. The 1000 top-ranking CpG islands were then subject to Locus Overlap Analysis (LOLA) for enrichment of genomic ranges, while signaling pathway analysis was carried out on the top 100 differentially methylated CpG islands. Differential methylation analysis illustrated that the most differentially methylated CpG islands in warts lay within the ITGB5, DTNB, RBFOX3, SLC6A9, and C2orf27A genes. In addition, the most enriched genomic region sets in warts were Sheffield's tissue-clustered DNase hypersensitive sites, ENCODE's segmentation and transcription factor binding sites, codex sites, and the epigenome sites from cistrome. Lastly, signaling pathway analysis showed that the GRB2, GNB1, NTRK1, AXIN1, and SKI genes were the most common regulators of the genes associated with the top 100 most differentially methylated CpG islands in warts. Our study shows that HPV-induced cutaneous warts have a clear CpG island methylation profile that sets them apart from normal skin. Such a finding could account for the temporary nature of warts and the capacity for individuals to undergo clinical remission.
A novel 12 bp deletion in the ITGB5 gene is strongly associated with Escherichia coli F4ac adhesion and increased susceptibility to infection in pigs
LIVESTOCK SCIENCE
Authors: Liu, Y.; Fu, W. X.; Wang, W. W.; Zhou, C. L.; Ding, X. D.; Zhang, Q.
Abstract
The bacterial strain enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbriae is the major pathogen causing potentially fatal diarrhoea in neonatal and recently-weaned piglets. Our previously published results from a genome wide association study (GWAS) of the pig genome identified a promising candidate gene (ITGB5) for predicting the susceptibility to ETEC F4ab/ac infection, the gene encoding the integrin beta 5 (ITGB5) receptor. We report here the assembly and cloning of the complete porcine ITGB5 gene based on the latest reference sequence for swine, as well as our results following analysis of the coding regions of ITGB5 from a sample of pigs that included both resistant and susceptible animals. We identified a novel 12 bp deletion in the 5' UTR region of the gene that correlates perfectly with increased ETEC F4ac adhesion in pig gut epithelial cells, in sample of 335 pigs from 3 different breeds. These results indicate that the ITGB5 gene is an important adhesion molecule for E. coli F4ac, and that the 12 bp deletion could serve as a genetic marker for selecting against susceptible pigs in breeding programs. (C) 2014 Published by Elsevier B.V.