Studies on the temporal,structural,and interacting features of the clubroot resistance gene Rcr1 using CRISPR/Cas9-based systems

Clubroot disease is a severe threat to Brassica crops globally,particularly in western Canada.Genetic resistance,achieved through pyramiding clubroot resistance(CR)genes with different modes of action,is the most important strategy for managing the disease.However,studies on the CR gene functions are quite limited.In this study,we have conducted investigations into the temporal,structural,and interacting features of a newly cloned CR gene,Rcr1,using CRISPR/Cas9 technology.For temporal functionality,we developed a novel CRISPR/Cas9-based binary vector,pHHIGR-Hsp18.2,to deliver Rcr1 into a susceptible canola line(DH12075)and observed that early expression of Rcr1 is critical for conferring resistance.For structural functionality,several independent mutations in specific domains of Rcr1 resulted in loss-offunction,highlighting their importance for CR phenotype.In the study of the interacting features of Rcr1,a cysteine protease gene and its homologous allele in canola were successfully disrupted via CRISPR/Cas9 as an interacting component with Rcr1 protein,resulting in the conversion from clubroot resistant to susceptible in plants carrying intact Rcr1.These results indicated an indispensable role of these two cysteine proteases in Rcr1-mediated resistance response.This study,the first of its kind,provides valuable insights into the functionality of Rcr1.Further,the new vector p HHIGR-Hsp18.2 demonstrated an inducible feature on the removal of add-on traits,which should be useful for functional genomics and other similar research in brassica crops.

Understanding host-microbial interactions in rumen：searching the best opportunity for microbiota manipulation

Ruminants utilize a wide variety of dietary substrates that are not digestible by the mammals, through microbial fermentation taking place in the rumen. Recent advanced molecular based approaches have allowed the characterization of rumen microbiota and its compositional changes under various treatment conditions.However, the knowledge is still limited on the impacts of variations in the rumen microbiota on host biology and function. This review summarizes the information to date on host-microbial interactions in the rumen and how we can apply such information to seek the opportunities to enhance the animal performance through manipulating the rumen function.

Gene-diet interactions in gastric cancer risk: A systematic review

AIM:To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.METHODS:A literature search was conducted in PubMed,EMBASE,and MEDLINE for articles published between January 2000 and July 2013,and 38 studies were identified.Previous studies included various dietary factors(e.g.,fruits and vegetables,soybean products,salt,meat,and alcohol)and genetic variants that are involved in various metabolic pathways.RESULTS:Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants.Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region.However,most previous studies have limitations,such as a small sample size and a retrospective casecontrol design.In addition,past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis.CONCLUSION:Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

AIM: To study the inflammatory bowel disease-5 locus (IBD5) and interleukin-23 receptor (IL23R) gene variants in UC patients and test for gene-gene interaction.

Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

Gene-gene,gene-environment,gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.

Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels

Objectives Apolipoprotein(Apo) A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15 -89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol (TC),TG,high-density lipoprotein cholesterol(HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs) were not different between the two groups.The levels of TG in non-drinkers, and TC,TG,low-density lipoprotein cholesterol (LDL-C)and ApoB in drinkers were different among the three -1131T】C genotypes(P【0.05-0.001).The -1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all), but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types (P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T, G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05) associated at the global level with TC,TG,HDL-C, LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with -1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with -1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and -1131T】C, c.553G】T and c.457G】A to detect the interactions of the ApoA5

GST family genes in jujube actively respond to phytoplasma infection

Jujube witches’broom(JWB)caused by phytoplasma has a severely negative effect on multiple metabolisms in jujube.The GST gene family in plants participates in the regulation of a variety of biotic and abiotic stresses.This study aims to identify and reveal the changes in the jujube GST gene family in response to phytoplasma infection.Here,70 ZjGSTs were identified in the jujube genome and divided into 8 classes.Among them,the Tau-class,including 44 genes,was the largest.Phylogenetic analysis indicated that Tau-class genes were highly conserved among species,such as Arabidopsis,cotton,chickpea,and rice.Through chromosome location analysis,37.1%of genes were clustered,and 8 of 9 gene clusters were composed of Tau class members.Through RT-PCR,qRT-PCR and enzyme activity detection,the results showed that the expression of half(20/40)of the tested ZjGSTs was inhibited by phytoplasma infection in field and tissue culture conditions,and GST activity was also significantly reduced.In the resistant and susceptible varieties under phytoplasma infection,ZjGSTU49-ZjGSTU54 in the cluster IV showed opposite expression patterns,which may be due to functional divergence during evolution.Some upregulated genes(ZjGSTU45,ZjGSTU49,ZjGSTU59,and ZjGSTU70)might be involved in the process of jujube against JWB.The yeast two-hybrid results showed that all 6 Tauclass proteins tested could form homodimers or heterodimers.Overall,the comprehensive analysis of the jujube GST gene family revealed that ZjGSTs responded actively to phytoplasma infection.Furthermore,some screened genes(ZjGSTU24,ZjGSTU49-52,ZjGSTU70,and ZjDHAR10)will contribute to further functional studies of jujube-phytoplasma interactions.

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

The Impact of Lipid-metabolizing Genetic Polymorphisms on Body Mass Index and Their Interactions with Soybean Food Intake: A Study in a Chinese Population

Objective To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index （BMI）, and estimate their interactions with soybean food intake. Methods A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. Results The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly hisher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 （95% confidence interval： 1.15-2.34, P〈0.01） after adjusting for the common confounders. Conclusion Our study has sugsested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.RESULTS A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer

AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557 , rs4880), Helicobacter pylori (H. pylori ) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557 ) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880 ) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD216Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD216Ala/genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/genotype, SOD2-16Ala/genotype, alcohol drinking, positive family history and type Ⅰ H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/genotype and SOD2-16Ala/genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.

DeepCBA:A deep learning framework for gene expression prediction in maize based on DNA sequences and chromatin interactions

Chromatin interactions create spatial proximity between distal regulatory elements and target genes in the genome,which has an important impact on gene expression,transcriptional regulation,and phenotypic traits.To date,several methods have been developed for predicting gene expression.However,existing methods do not take into consideration the effect of chromatin interactions on target gene expression,thus potentially reducing the accuracy of gene expression prediction and mining of important regulatory elements.In this study,we developed a highly accurate deep learning-based gene expression prediction model(DeepCBA)based on maize chromatin interaction data.Compared with existing models,DeepCBA exhibits higher accuracy in expression classification and expression value prediction.The average Pearson correlation coefficients(PCCs)for predicting gene expression using gene promoter proximal interactions,proximaldistal interactions,and both proximal and distal interactions were 0.818,0.625,and 0.929,respectively,representing an increase of 0.357,0.16,and 0.469 over the PCCs obtained with traditional methods that use only gene proximal sequences.Some important motifs were identified through DeepCBA;they were enriched in open chromatin regions and expression quantitative trait loci and showed clear tissue specificity.Importantly,experimental results for the maize flowering-related gene ZmRap2.7 and the tillering-related gene ZmTb1 demonstrated the feasibility of DeepCBA for exploration of regulatory elements that affect gene expression.Moreover,promoter editing and verification of two reported genes(ZmCLE7 and ZmVTE4)demonstrated the utility of DeepCBA for the precise design of gene expression and even for future intelligent breeding.DeepCBA is available at http://www.deepcba.com/or http://124.220.197.196/.

Interactions between CagA and smoking in gastric cancer

AIM: To examine the interactions between cytotoxinassociated gene (CagA) positive Helicobacter pylori infection and smoking in non-cardiac gastric cancer.METHODS: A case-control study (257 cases and 514 frequency-matched controls) was conducted from September 2008 to July 2010 in Xi’an,China.Cases were newly diagnosed,histologically confirmed non-cardiac cancer.Controls were randomly selected from similar communities to the cases and were further matched by sex and age (± 5 years).A face-to-face interview was performed by the investigators for each participant.Data were obtained using a standardized questionnaire that included questions regarding known or suspected lifestyle and environmental risk factors of gastric cancer.A 5 mL sample of fasting venous blood was taken.CagA infection was serologically detected by enzymelinked immunosorbent assays.RESULTS: Smoking and CagA infection were statistically significant risk factors of non-cardiac cancer.CagA was categorized in tertiles,and the odds ratio (OR) was 12.4 (95% CI: 6.1-20.3,P = 0.003) for CagA after being adjusted for confounding factors when the highexposure category was compared with the low-exposure category.Smokers had an OR of 5.4 compared with subjects who never smoked (95% CI: 2.3-9.0,P = 0.002).The OR of non-cardiac cancer was 3.5 (95% CI: 1.8-5.3) for non-smokers with CagA infection,3.5 (95% CI: 1.9-5.1) for smokers without CagA infection,and 8.7 (95% CI: 5.1-11.9) for smokers with CagA infection compared with subjects without these risk factors.After adjusting for confounding factors,the corresponding ORs of non-cardiac cancer were 3.2 (95% CI: 1.5-6.8),2.7 (95% CI: 1.3-4.9) and 19.5 (95% CI: 10.3-42.2),respectively.There was a multiplicative interaction between smoking and CagA,with a synergistic factor of 2.257 (Z = 2.315,P = 0.021).CONCLUSION: These findings support a meaningful interaction between CagA and smoking for the risk of gastric cancer which may have implications for its early detection.

Interaction between early in ovo stimulation of the gut microbiota and chicken host-splenic changes in gene expression and methylation

Background:Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA.Methylated CpG regions within the gene promoters lead to silencing of the gene expression in most cases.Factors contributing to epigenetic regulation include intestinal microbiota,which in chicken can be potently modified by in ovo stimulation.The main aim of this study was to determine global and specific methylation patterns of the spleen under the influence of host-microbiome interaction.Results:Fertilized eggs of two genotypes:Ross 308 and Green-legged Partridgelike were in ovo stimulated on d 12 of incubation.The injected compounds were as follows:probiotic-Lactococcus lactis subsp.cremoris IBB477,prebiotic-galactooligosaccharides,and synbiotic-combination of both.Chickens were sacrificed on d 42 post-hatching.Spleen was collected,RNA and DNA were isolated and intended to gene expression,gene methylation and global methylation analysis.We have proved that negative regulation of gene expression after administration of bioactive substances in ovo might have epigenetic character.Epigenetic changes depend on the genotype and the substance administered in ovo.Conclusion:Epigenetic nature of microbial reprogramming in poultry and extension of issues related to hostmicrobiome interaction is a new direction of this research.

Interaction and Relationship Between Angiotensin ConvertingEnzyme Gene and Environmental Factors Predisposing toEssential Hypertension in MongolianPopulation of China

Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.

Gene-environment interaction and male reproductive function

As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.

Genome-Wide Identification,Expression Profiling and Protein-Protein Interaction Properties of the BEL-Like Homeodomain Gene Family in Apple

BEL1-like homeodomain(BLH)family proteins are homeodomain transcription factors,which are found ubiquitously in plants and play important roles in regulating meristem and flower development.Although BLH proteins have been reported in some plant species,there is very little information available for plants in the Malus genus(e.g.,apple tree:Malus domestica).In the present study,we identified 19 apple MdBLH genes.Phylogenetic analysis revealed that the MdBLH genes could be divided into five groups.Analysis of gene structure showed that MdBLH gene has four exons,and the third exon was 61 bp in length.Chromosomal location analysis suggested that the MdBLH genes are not distributed uniformly on 12 chromosomes.Eleven MdBLH genes were cloned by RT-PCR,and their expression patterns were also determined.Among them,the expression levels of MdBLH4.1 and MdBLH9.1 could be induced by sodium chloride stress,while the expression levels of MdATH1.1,MdBLH8.1,MdBLH8.3,and MdBLH11.1 were down-regulated by such stress.Transcriptional levels of MdATH1.1 and MdBLH7.2 were down-regulated by mannitol stress.The result of yeast two-hybrid experiment showed that MdBEL1.1 interacted with apple ovate family proteins 6(MdOFP6),and MdBLH3.1 interacted with the MdOFP4,MdOFP6,MdOFP13,and MdOFP16 proteins.Our results provide a strong theoretical basis and a valuable reference for analyzing of the biological functions of MdBLH proteins as transcription factors in apple growth,development,and stress and also for the construction of regulatory networks.

Role of a Signalling System in Gene Interaction in Inheritance of Root System Characteristics of Arabidopsis thaliana (L.) Heynh.

The central problem of genetics is gene interaction since genes in the course of individual organism development interact with other genes, that’s why their effects may change. Studies for the last 100 years managed to discover that the entire diversity of inter-gene interactions is presented in four major forms: complementarity, epistasis, polymery, and modifying effect of genes. However, gene interaction mechanism which is reflected on the segregation nature of variously crossed hybrids has not been sufficiently studied. Exclusive of molecular genetics, biochemistry and physiology, a genetic analysis of inheritance of characteristics in gene interaction taken by itself cannot reveal nature of this interaction. Lately, molecular-genetic and physiological studies on A. thaliana mutants have enabled to isolate and sequence a wide range of genes controlling certain links of the signalling chain. At the same time, effect of the plant development regulation signalling system on interaction of these genes in inheritance of characteristics of Arabidopsis root system haven’t been studied so far which was a cause for our studies. Gene interaction problem is closely related to the plant development regulation signalling system. Mechanism involved in gene interaction may be explained based on current idea of molecular principles of biological response. Affected by mutations occurring in various genes that control certain links of the signalling chain, signalling path to the cell nucleus and response are blocked partially or in full which leads to distortion in expression of the characteristic on the plant level in general or its organ level. Such phenomenon is observed in realization of many characteristics in animals and plants, including in A. thaliana. In inheritance of such characteristics, as a rule, both allelic, and non-allelic gene interactions are observed. Results of a study of the plant signalling system interconnection and gene interaction in inheritance of characteristics of Arabidopsis root system are presented. It is established that complementary interaction of genes RHD3 and SAR1 is observed in the second crossing generation for plants of rhd3-1 × sar-1 mutant lines. When gpa1-3 × slr-1 mutant-line plants are crossed, recessive epistasis (slr-1 slr-1 > GPA1_) occurs in F2 generation. Polymeric interaction of genes SHY2 and MSG1 is observed in F2 in crossing of shy2-2 × msg1-2 mutant-line plants.