Patients with Behçet's disease (BD) suffer from episodic inflammation often affecting the orogenital mucosa, skin, and eyes. To discover new BD-susceptibility loci, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish BD patients and 1,278 controls. We identified novel associations at CCR1, STAT4, and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln, recessively conferred disease risk. These findings replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis p < 2 × 10−9). We also found evidence for interaction between HLA-B*51 and ERAP1 (p = 9 × 10−4). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (MHC-I, ERAP1, and IL23R, and the MHC-I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and BD.
Halomonas smyrnensis AAD6T is a gram negative, aerobic, and moderately halophilic bacterium, and is known to produce high levels of levan with many potential uses in foods, feeds, cosmetics, pharmaceutical and chemical industries due to its outstanding properties. Here, the whole-genome analysis was performed to gain more insight about the biological mechanisms, and the whole-genome organization of the bacterium. Industrially crucial genes, including the levansucrase, were detected and the genome-scale metabolic model of H. smyrnensis AAD6T was reconstructed. The bacterium was found to have many potential applications in biotechnology not only being a levan producer, but also because of its capacity to produce Pel exopolysaccharide, polyhydroxyalkanoates, and osmoprotectants. The genomic information presented here will not only provide additional information to enhance our understanding of the genetic and metabolic network of halophilic bacteria, but also accelerate the research on systematical design of engineering strategies for biotechnology applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1184-3) contains supplementary material, which is available to authorized users.
Increases in NK1/NK2 ratio and CD16IFN-γ NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells.
Turkey b Halomonas smyrnensis AAD6T is a Gram-negative, aerobic, exopolysaccharide-producing, and moderately halophilic bacterium that produces levan, a fructose homopolymer with many potential uses in various industries. We report the draft genome sequence of H. smyrnensis AAD6 T , which will accelerate research on the rational design and optimization of microbial levan production. H alomonas smyrnensis AAD6T was isolated from soil samples taken from the Çamaltı Saltern area (Turkey) and was found to excrete high levels of levan exopolysaccharide (5). Further research on the potential uses of levan produced by Halomonas sp. as a bioflocculating agent (7), its nanostructured thin films (9), its suitability for peptide-based drug nanocarrier systems (8), and a scheme for economical production from waste (4) have been reported. Moreover, the first genome scale metabolic model of Chromohalobacter salexigens DSM 3043 was reported, which in turn formed the basis for the reconstruction of a generic in silico metabolic model of levan-producing Halomonas sp. (1). Recently, H. smyrnensis strain AAD6T was identified as a Gram-negative, nonmotile, dark-yellow-pigmented, aerobic, moderately halophilic bacterium (6).In this study, whole-genome sequencing of H. smyrnensis AAD6 T was performed by using a combination of 454 GS FLXϩ (454 Life Sciences, Branford, CT) and Ion Proton (Ion Torrent Systems, Inc., Guilford, CT) sequencers. The shotgun sequence data generated consisted of 1,082,564 reads (mean length of 498.36 bp) and 359,877 reads (mean length of 122.42 bp), respectively, providing 140-fold coverage. The duplicates in the sequence data were eliminated with CLC Genomics Workbench (v5.0.1). De novo assembly of the whole sequencing reads was carried out with Newbler Assembler (v2.3). One hundred ninetytwo contigs, with a minimum length of 500 bp, were obtained. Alignment of these contigs and elimination of the overlaps using Sequencher 5.0 (3) resulted in 81 high-quality contigs. These contigs were mapped to the raw data with CLC Genomics Workbench (v5.0.1) to estimate the terminals, and using overlapping terminal regions, the contigs were assembled into 34 supercontigs via Geneious Pro (v5.5.6) software. The draft genome of H. smyrnensis AAD6T was structured with 34 supercontigs (total assembly size of 3,561,919 bp). Gene prediction and annotation were carried out using the RAST server (2).The draft genome that resulted had a mean GC content of 67.9%, 3,237 coding sequences, 1,756 subsystems, and 64 RNA genes. Putative functions could be assigned to 2,436 protein-coding genes, whereas 801 hypothetical proteins had no match to any known proteins. Genome analysis revealed a number of genes related to exopolysaccharide biosynthesis, including the genes for levansucrase and ExoD.Phylogenetic analysis of the draft genome revealed a rather close relationship to other species of the genus Halomonas, where Halomonas salina (99.5%) and Halomonas halophila (99.5%) were found to be the closest species on the basis of 16S rRNA sequ...
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