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1.
Kazuyuki Abe Yutaka Nakamura Kohei Yamauchi Makoto Maemondo 《Clinical and molecular allergy : CMA》2018,16(1):9
Background
Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1) are associated with bronchial severity and pulmonary function. CHI3L1 proteins are involved in both innate and adaptive immune responses; however, to date, the correlation of these SNPs and their age of onset of bronchial asthma has not been demonstrated.Methods
To address the role of these genetic variations, 390 patients with well-controlled bronchial asthma and living in Japan were recruited, genotyped, and had a pulmonary function test performed on them in this study. To analyze the concentration levels of CHI3L1 protein, bronchial lavage fluids were examined.Results
Forced expiratory volume in one second, %predicted (%FEV1), was significantly decreased in homozygotes of rs1214194 compared to heterozygotes and wild type. The age of onset of adult bronchial asthma was significantly younger in GG homozygotes of rs4950928 and AA homozygotes of rs1214194 than in the other two genotypes. The concentration of CHI3L1 protein in bronchial lavage fluid increased in both homozygotes of rs4950928 and rs1214194.Conclusions
Our study demonstrated that the homozygotes of rs4950928 and rs1214194 of CHI3L1 might predict an early onset of bronchial asthma and have the propensity to promote airway remodeling.Trial registration JMA-IIA00045 remodeling-ICS2.
Magdalena Lindén Jorge I. Ramírez Sepúlveda Tojo James Gudny Ella Thorlacius Susanna Brauner David Gómez-Cabrero Ingrid Kockum Marie Wahren-Herlenius 《Biology of sex differences》2017,8(1):34
Background
Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects.Methods
We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term.Results
We found ten SNPs affecting the expression of 16 different genes (FDR <?0.05). rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus).Conclusions
We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases.3.
Mang Ching Lai Anne-Laure Bechy Franziska Denk Emma Collins Maria Gavriliouk Judith B. Zaugg Brent J. Ryan Richard Wade-Martins Tara M. Caffrey 《Molecular neurodegeneration》2017,12(1):79
Background
Genome wide association studies have identified microtubule associated protein tau (MAPT) H1 haplotype single nucleotide polymorphisms (SNPs) as leading common risk variants for Parkinson’s disease, progressive supranuclear palsy and corticobasal degeneration. The MAPT risk variants fall within a large 1.8 Mb region of high linkage disequilibrium, making it difficult to discern the functionally important risk variants. Here, we leverage the strong haplotype-specific expression of MAPT exon 3 to investigate the functionality of SNPs that fall within this H1 haplotype region of linkage disequilibrium.Methods
In this study, we dissect the molecular mechanisms by which haplotype-specific SNPs confer allele-specific effects on the alternative splicing of MAPT exon 3. Firstly, we use haplotype-hybrid whole-locus genomic MAPT vectors studies to identify functional SNPs. Next, we characterise the RNA-protein interactions at two loci by mass spectrometry. Lastly, we knockdown candidate splice factors to determine their effect on MAPT exon 3 using a novel allele-specific qPCR assay.Results
Using whole-locus genomic DNA expression vectors to express MAPT haplotype variants, we demonstrate that rs17651213 regulates exon 3 inclusion in a haplotype-specific manner. We further investigated the functionality of this region using RNA-electrophoretic mobility shift assays to show differential RNA-protein complex formation at the H1 and H2 sequence variants of SNP rs17651213 and rs1800547 and subsequently identified candidate trans-acting splicing factors interacting with these functional SNPs sequences by RNA-protein pull-down experiment and mass spectrometry. Finally, gene knockdown of candidate splice factors identified by mass spectrometry demonstrate a role for hnRNP F and hnRNP Q in the haplotype-specific regulation of exon 3 inclusion.Conclusions
We identified common splice factors hnRNP F and hnRNP Q regulating the haplotype-specific splicing of MAPT exon 3 through intronic variants rs1800547 and rs17651213. This work demonstrates an integrated approach to characterise the functionality of risk variants in large regions of linkage disequilibrium.4.
Shouquan Wu Yu Wang Guo Chen Miaomiao Zhang Minggui Wang Jian-Qing He 《BMC pulmonary medicine》2018,18(1):180
Background
2′-5′-Oligoadenylate synthetase 1 (OAS1) plays an important role in inflammatory immune reactions. OAS1 polymorphisms have been associated with increased susceptibility to various diseases. We investigated the association of polymorphisms in OAS1 with tuberculosis (TB).Methods
A total of 1215?TB cases and 1114 healthy controls were enrolled from two independent studies. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method. Associations between OAS1 polymorphisms (rs2240190, rs1131454, 10,774,671 and 11,066,453) and TB risk were established based on distributions of allelic frequencies using different genetic models.Results
Significant association was observed between rs10774671, rs1131454 and TB. In the initial study, the G allele of rs10774671 was a significantly protective factor against TB (P?=?0.006) and the genotype of GG differed significantly between TB patients and controls under the codominant model (P?=?0.008) after Bonferroni correction. In the validation study, we also observed that the rs10774671 G allele (P?=?0.001) and GG genotype (P?=?0.001) were associated with TB. In addition, we found that the rs1131454 G allele (P?=?0.004) and GG genotype (P?=?0.001) were protective against TB in the Chinese Han population.Conclusions
We report novel associations of polymorphisms in OAS1 with TB in the Chinese Tibetan and Han populations. Similar studies in different populations and functional studies are warranted to confirm our results.5.
Background
Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test. For this analysis, we used 7211 and 2838 genotyped study subjects for discovery and replication, respectively. We also performed a multiple-genotype and multiple-phenotype analysis of a gene-based single-nucleotide polymorphism (SNP) set.Results
We found an association between metabolic syndrome and an intronic SNP pair, rs7107152 and rs1242229, in SIDT2 gene at 11q23.3. Both SNPs correlate with the expression of SIDT2 and TAGLN, whose products promote insulin secretion and lipid metabolism, respectively. This SNP pair showed statistical significance at the replication stage.Conclusions
Our findings provide insight into an underlying mechanism that contributes to metabolic syndrome.6.
Zhengling Liu Zengyan Wang Changhong Hao Yonghui Tian Jingjing Fu 《Reproductive biology and endocrinology : RB&E》2018,16(1):120
Background
Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.Methods
Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results
Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.Conclusions
Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.7.
Gholamreza?Daryabor Mahdi?Mahmoudi Ahmadreza?Jamshidi Keramat?Nourijelyani Aliakbar?Amirzargar Nooshin?Ahmadzadeh Elham?Farhadi Mohammad?Hossein?Nicknam
Introduction
The result of recent genome-wide association studies revealed that, in addition to HLA-B27, a few non-HLA genes are associated with susceptibility to ankylosing spondylitis (AS) in Caucasian populations. According to these studies, IL-23R is one of the genes that is associated with AS. In this study, we evaluated five important single nucleotide polymorphisms (SNPs) of the IL-23R gene which confers susceptibility to AS, and its effects on the severity of the disease in HLA-B27 positive and negative patients and several subtypes of HLA-B27.Materials and methods
The study population consisted of 294 AS patients and 352 age-, sex-, and ethnicity-matched healthy controls. All patients were examined by rheumatologists, and met modified,NewYork criteria for the disease. Five SNPs (rs1004819, rs11209032, rs1495965, rs11465804, and rs1004819) of the IL-23R gene were genotyped using the Real-Time PCR TaqMan genotyping method.Results
We found that only rs1004819 has a significant association with AS, and that the remaining four SNP alleles are not associated with AS. Also, there was no association between these five polymorphisms and BASDAI, BASFI, and BASMI indices. Two haplotypes, ACGAT and ACGAG, were found to be associated with the heritability of AS. In addition, two significant, protective diplotypes (D8, \(\frac{{GCGAG}}{{GTGGG}}\); and D9, \(\frac{{ACGAG}}{{GCGAG}}\)) were discovered.Conclusion
This study supported our previous findings regarding the differences between the genetic patterns of AS in Iranian patients compared with those in other parts of the world.8.
Background
After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population.Methods
Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2.Results
A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR?=?2.924, P?=?2.3E?06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR?=?0.08033, P?=?2.11E?09) and dominant models (OR?=?0.05359, P?=?4.15E?11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR?=?20.05, P?=?2.74 E?12) and recessive models (OR?=?22.24, P?=?6.811E?10).Conclusions
Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.9.
Zexi Cai Trine Michelle Villumsen Torben Asp Bernt Guldbrandtsen Goutam Sahana Mogens Sandø Lund 《BMC genetics》2018,19(1):103
Background
Identification of genes underlying production traits is a key aim of the mink research community. Recent availability of genomic tools have opened the possibility for faster genetic progress in mink breeding. Availability of mink genome assembly allows genome-wide association studies in mink.Results
In this study, we used genotyping-by-sequencing to obtain single nucleotide polymorphism (SNP) genotypes of 2496 mink. After multiple rounds of filtering, we retained 28,336 high quality SNPs and 2352 individuals for a genome-wide association study (GWAS). We performed the first GWAS for body weight, behavior, along with 10 traits related to fur quality in mink.Conclusions
Combining association results with existing functional information of genes and mammalian phenotype databases, we proposed WWC3, MAP2K4, SLC7A1 and USP22 as candidate genes for body weight and pelt length in mink.10.
Peng Huang Haozhi Fan Ting Tian Peiwen Liao Jun Li Rongbin Yu Xueshan Xia Yue Feng Jie Wang Yuan Liu Yun Zhang Ming Yue 《Virology journal》2017,14(1):235
Background
Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.Methods
The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.Results
Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR?=?1.33, 95% CI: 1.04–1.71, P?=?0.026) and additive models (adjusted OR?=?1.30, 95% CI: 1.06–1.60, P?=?0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR?=?1.52, 95% CI: 1.01–2.28, P?=?0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR?=?1.37, 95% CI: 1.05–1.78, P?=?0.018).Conclusion
The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.11.
Chih-Yueh Liu Chang-Ching Weng Chih-Hsiang Lin Chiou-Ying Yang Kwok-Kong Tony Mong Yaw-Kuen Li 《Biotechnology letters》2017,39(3):407-413
Objectives
A Neissaria bacterial pilus sugar, bacillosamine, was synthesized and, for the first time, used as a probe to screen a single-chain variable fragment (scFv).Results
Four Neisseria, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria sicca and Neisseria subflava, and two negative controls, Streptococcus pneumoniae and Escherichia coli, were tested through ELISA, immunostaining and gold nanoparticle immunological assay. All results indicated that the selected scFv is feasible for the specific detection of Neisseria species via the recognition of bacillosamine.Conclusions
The recombinant scFv could detect Neisseria strains at 106 CFU/ml.12.
BACKGROUND
Microbes affect the growth of plants. In this study, the diversity and plant growth-supporting activities of wheat rhizospheric bacteria were examined.METHODS
Sampling was performed thrice at different phases of plant growth. Microbes associated with the rhizoplane of three wheat varieties (Seher, Lasani, and Faisalabad) were cultured and assessed for their plant growth-promoting abilities based on auxin production, hydrogen cyanide production, phosphate solubilization, and nitrogen fixation.RESULTS
Bacterial load (CFU/mL) declined, and the succession of bacterial diversity occurred as the plants aged. Most auxin-producing bacteria and the highest concentrations of auxin (77 μg/mL) were observed during the second sampling point at the tillering stage. The Seher variety harbored the most auxin-producing as well as phosphate-solubilizing bacteria. Most of the bacteria belonged to Bacillus and Pseudomonas. Planomicrobium, Serratia, Rhizobium, Brevundimonas, Stenotrophomonas, and Exiguobacterium sp. were also found.CONCLUSION
These results suggest that the rhizoplane microbiota associated with higher-yield plant varieties have better plant growth-promoting abilities as compared to the microbiota associated with lower-yield plant varieties.13.
Nicholas J. Bond Albert Koulman Julian L. Griffin Zoe Hall 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):128
Introduction
Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.Objectives
We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.Methods
massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.Results
Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.Conclusion
massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.14.
Korey J. Brownstein Mahmoud Gargouri William R. Folk David R. Gang 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):133
Introduction
Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.Objectives
We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.Methods
Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.Results
Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.Conclusions
Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.15.
Yibin Zhuang Jingjie Jiang Huiping Bi Hua Yin Shaowei Liu Tao Liu 《Biotechnology letters》2016,38(4):619-627
Objectives
To produce rosmarinic acid analogues in the recombinant Escherichia coli BLRA1, harboring a 4-coumarate: CoA ligase from Arabidopsis thaliana (At4CL) and a rosmarinic acid synthase from Coleus blumei (CbRAS).Results
Incubation of the recombinant E. coli strain BLRA1 with exogenously supplied phenyllactic acid (PL) and analogues as acceptor substrates, and coumaric acid and analogues as donor substrates led to production of 18 compounds, including 13 unnatural RA analogues.Conclusion
This work demonstrates the viability of synthesizing a broad range of rosmarinic acid analogues in E. coli, and sheds new light on the substrate specificity of CbRAS.16.
Yanping Zhou Wiktor Lisowski Yan Zhou Ng Wun Jern Kama Huang Eileen Fong 《Biotechnology letters》2017,39(10):1509-1514
Objectives
To improve its phosphate accumulating abilities for phosphate recycling from wastewater, a magnetotactic bacterium, Magnetospirillum gryphiswaldense, was genetically modified to over-express polyphosphate kinase.Results
Polyphosphate kinase was over-expressed in the bacterium. The recombinant strain accumulated ninefold more polyphosphate from synthetic wastewater compared to original wild type. The magnetic property of the recombinant M. gryphiswaldense strain was retained.Conclusions
The recombinant M. gryphiswaldense can be used for phosphate removal and recovery in bioremediation.17.
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19.
Debleena Guin Manish Kumar Mishra Puneet Talwar Chitra Rawat Suman S. Kushwaha Shrikant Kukreti Ritushree Kukreti 《BMC medical genomics》2017,10(1):56
Background
PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A systematic review for LR was conducted for ADR, and drug efficacy, independently. All included articles were assessed for methodological quality on 14 parameters. GWAS of PD were also reviewed. Protein-protein interaction (PPI) analysis using STRING and functional enrichment using WebGestalt was performed to explore the common link between LR and PD.Results
From 37 candidate studies on levodopa toxicity, 18 genes were found associated, of which, CAn STR 13, 14 (DRD2) was most significantly associated with dyskinesia, followed by rs1801133 (MTHFR) with hyper-homocysteinemia, and rs474559 (HOMER1) with hallucination. Similarly, 8 studies on efficacy resulted in 4 genes in which rs28363170, rs3836790 (SLC6A3) and rs4680 (COMT), were significant. To establish the molecular connection between LR with PD, we identified 35 genes significantly associated with PD. With 19 proteins associated with LR and 35 with PD, two independent PPI networks were constructed. Among the 67 nodes (263 edges) in LR, and 62 nodes (190 edges) in PD pathophysiology, UBC, SNCA, FYN, SRC, CAMK2A, and SLC6A3 were identified as common potential candidates.Conclusion
Our study revealed the genetically significant polymorphism concerning the ADRs and levodopa efficacy. The six common genes may be used as predictive markers for therapy optimization and as putative drug target candidates.20.