Genomic Variants in NEURL, GJA1 and CUX2 Significantly Increase Genetic Susceptibility to Atrial Fibrillation
SCIENTIFIC REPORTS
Authors: Wang, Pengxia; Qin, Weixi; Wang, Pengyun; Huang, Yufeng; Liu, Ying; Zhang, Rongfeng; Li, Sisi; Yang, Qin; Wang, Xiaojing; Chen, Feifei; Liu, Jingqiu; Yang, Bo; Cheng, Xiang; Liao, Yuhua; Wu, Yanxia; Ke, Tie; Tu, Xin; Ren, Xiang; Yang, Yanzong; Xia, Yunlong; Luo, Xiaoping; Liu, Mugen; Li, He; Liu, Jingyu; Xiao, Yi; Chen, Qiuyun; Xu, Chengqi; Wang, Qing K.
Abstract
Atrial fibrillation (AF) is the most common arrhythmia. In 2014, two new meta-GWAS identified 5 AF loci, including the NEURL locus, GJA1 locus, CAND2 locus, and TBX5 locus in the European ancestry populations and the NEURL locus and CUX2 locus in a Japanese population. The TBX5 locus for AF was reported by us in 2013 in the Chinese population. Here we assessed the association between AF and SNPs in the NEURL, GJA1, CAND2 and CUX2 loci in the Chinese Han population. We carried out a large case-control association study with 1,164 AF patients and 1,460 controls. Significant allelic and genotypic associations were identified between NEURL variant rs6584555 and GJA1 variant rs13216675 and AF. Significant genotypic association was found between CUX2 SNP rs6490029 and AF. No association was found between CAND2 variant rs4642101 and AF, which may be due to an insufficient power of the sample size for rs4642101. Together with our previous findings, seven of fifteen AF loci (<50%) identified by GWAS in the European ancestry populations conferred susceptibility to AF in the Chinese population, and explained approximately 14.5% of AF heritability. On the other hand, two AF loci identified in the Japanese population were both replicated in the Chinese population.
Analysis of DNA Methylation and Hydroxymethylation in the Genome of Crustacean Daphnia pulex
GENES
Authors: Strepetkaite, Dovile; Alzbutas, Gediminas; Astromskas, Eimantas; Lagunavicius, Arunas; Sabaliauskaite, Rasa; Arbaciauskas, Kestutis; Lazutka, Juozas
Abstract
The aim of our study was to analyze the presence of 5-methyl-cytosine (5-mC) and 5-hydroxymethyl-cytosine (5-hmC) in the genome of crustacean Daphnia pulex. First, the presence of 5-mC and 5-hmC in genomic DNA was demonstrated by using antibodies specific to either 5-mC or 5-hmC. Then, analysis of 5-mC and 5-hmC using pairs of restriction enzymes with different sensitivity to methylation and hydroxymethylation confirmed the presence of both modifications in selected regions of three genes (Cox4, Cand2 and Ephx1). To get a detailed picture of 5-hmC distribution over the D. pulex genome, we performed 5-hmC enrichment and sequenced the enriched fraction using next generation sequencing and non-enriched library (input) as a control. Comparison of input and enriched libraries showed that 5-hmC in exons is twice as frequent as in introns. Functional analysis indicated that 5-hmC abundance is associated with genes that are involved in the adenylate cyclase-activating G-protein-coupled receptor signaling pathway, molting cycles, morphogenesis and cell fate determination. Genes that lack 5-hmC tend to be involved in the regulation of the transforming growth factor beta receptor signaling pathway and in many mRNA-related processes. Our results suggest that epigenetic modifications are present in the genome of D. pulex and most likely are involved in the regulation of gene expression of this crustacean.