Research progress on the relationship between Paneth cellssusceptibility genes,intestinal microecology and inflammatory bowel disease

Inflammatory bowel disease(IBD)is a disorder of the immune system and intestinal microecosystem caused by environmental factors in genetically susceptible people.Paneth cells(PCs)play a central role in IBD pathogenesis,especially in Crohn's disease development,and their morphology,number and function are regulated by susceptibility genes.In the intestine,PCs participate in the formation of the stem cell microenvironment by secreting antibacterial particles and play a role in helping maintain the intestinal microecology and intestinal mucosal homeostasis.Moreover,PC proliferation and maturation depend on symbiotic flora in the intestine.This paper describes the interactions among susceptibility genes,PCs and intestinal microecology and their effects on IBD occurrence and development.

Association between 15 known or potential breast cancer susceptibility genes and breast cancer risks in Chinese women

Objective:There are many hereditary breast cancer patients in China,and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives.However,the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women.Methods:We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls.These breast cancer patients were unselected for age at diagnosis or family history.Results:We found that pathogenic variants in TP53[odds ratio(OR):16.9,95%confidence interval(CI):5.2–55.2];BRCA2(OR:10.4,95%CI:7.6–14.2);BRCA1(OR:9.7,95%CI:6.3–14.8);and PALB2(OR:5.2,95%CI:3.0–8.8)were associated with a high risk of breast cancer.ATM,BARD1,CHEK2,and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold.In contrast,pathogenic variants of NBN,RAD50,BRIP1,and RAD51C were not associated with increased risk of breast cancer in Chinese women.The pathogenic variants of PTEN,CDH1,and STK11 were very rare,so they had a limited contribution to Chinese breast cancer.Patients with pathogenic variants of TP53,BRCA1,BRCA2,and PALB2 more often had earlyonset breast cancer,bilateral breast cancer,and a family history of breast cancer and/or any cancer.Conclusions:This study provided breast cancer risk assessment data for multiple genes in Chinese women,which is useful for genetic testing and clinical management of Chinese hereditary breast cancer.

Physical Location of HelminthosporiumCarbonum Susceptibility Gene hm1 by FISH of a RFLP Marker umc119 in Maize

A fluorescencein situ hybridization (FISH) procedure was adopted to physically map a RFLP marker, umc119 near the centromere of the long arm of linkage group1 in maize. The hm1 gene (Helminthosporium carbonum susceptibility gene) was linked closely with the marker umc119. RFLP markers are very good landmarks for mapping genes. Therefore, we also determined the position of the gene hm1 on the chromosome based on the physical location of umc119. The disease induced by infection ofHelminthosporium carbonum is one of the serious maize diseases and it distributes in many countries including China. Hybridization sites were showed on 1 L (long arm of chromosome1) and 5 L. The percentage distance from centromere to the hybridization site was 22.86 on 1 L and 58.23 on 5 L the detection rate was about 12% for mitotic cells. In interphase nuclei five hybridized sites were detected. It demonstrated that umc119 was multiplicated sequences. FISH has more advantages overin situ hybridization (ISH) detected by DAB for increasing the detection ratio and contrast between chromosomes and hybridization signals. The ability to detect the hybridization signal of a small low copy DNA sequence is a very important key towards wide application of FISH for plant genome mapping.

Clinical significance of breast cancer susceptibility gene 1 expression in resected non-small cell lung cancer:A meta-analysis

BACKGROUND The clinical significance of breast cancer susceptibility gene 1(BRCA1)in nonsmall cell lung cancer(NSCLC)patients undergoing surgery remains unclear up to now.AIM To explore the relation of BRCA1 expression with clinicopathological characteristics and survival in patients with resected NSCLC.METHODS EMBASE,PubMed,Web of Science,and The Cochrane Library databases were searched to identify the relevant articles.To assess the correlation between the expression of BRCA1 and clinicopathological characteristics and prognosis of patients with resected NSCLC patients,the combined relative risks or hazard ratios(HRs)with their corresponding 95%confidence intervals[CIs]were estimated.RESULTS Totally,11 articles involving 1041 patients were included in the meta-analysis.The results indicated that the expression of BRCA1 was significantly correlated with prognosis of resected NSCLC.Positive BRCA1 expression signified a shorter overall survival(HR=1.60,95%CI:1.25-2.05;P<0.001)and disease-free survival(HR=1.78,95%CI:1.42-2.23;P<0.001).However,no significant association of BRCA1 expression with any clinicopathological parameters was observed.CONCLUSION BRCA1 expression indicates a poor prognosis in resected NSCLC patients.BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.

DELETION AND INACTIVATION OF RETINOBLASTOMA SUSCEPTIBILITY GENE IN PRIMARY RETINOBLASTOMA

The status and expression of Rb gene was detected and analyzed in 19 surgical retinoblastoma specimens using Rb cDNA 3. 8 kb and 0. 9 kb fragment as probe and antibodies specific for synthetic Rb peptide or expressive product of Rb gene expression plasmld. DNA from those tumors had the hemlzygous deletion in 3 cases, the homozygous internal deletion In 2 cases and alterated restriction fragment involving In one copy of Rb gene In 1 case. The quantity of Rb protein demonstrated either absence of reduction in all the 16 cases examined In comparison with that in normal adult retina. It suggested that there were structural or/ and functional defects of Rb gene In retinoblastoma cells and provided evidence to support Knudson' s two hit hypothesis.

Confirmation of susceptibility gene loci on chromosome 1 in Northern China Han families with type 2 diabetes

Objective To confirm previous effort to identify type 2 diabetes susceptibility genes in a Northern Chinese population by conducting a new genome scan with both an increased number of type 2 diabetes families and a new set of microsatellite markers within the previously localized regions.Methods A genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, we obtained size information for all loci , and then a further study was done by both parametric and non-parametric linkage analysis to investigate the P values and Z values of these loci.Results We surveyed 34 microsatellite markers which distributed within 5 regions along chromosome 1, and a total of 12?000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci. All P values of the 8 loci were lower than 0.05, and the highest Z value was 2.17. A very interesting finding is that all 5 markers at the p- terminal 1p36.3-1p36.23 region, spanning a long range of 16.9?cM, were identified to have a low P value of less than 0.05, which suggests that this region may contain multiple susceptibility genes. Regions 4 and 5 also confirmed the previous findings, and we narrowed these two regions to a 2.7?cM and 2.5?cM regions, respectively.Conclusions We further confirmed the results gained in the previous genome-wide scan using an increased number of NIDDM families and a new set of microsatellite markers lying within the initially localized regions. The fact that all 5 loci at the p- terminal region displayed a low P value of less than 0.05 suggests that more than 1 susceptibility gene may reside in this region.

Engineering broad-spectrum disease-resistant rice by editing multiple susceptibility genes

Rice blast and bacterial blight are important diseases of rice(Oryza sativa)caused by the fungus Magnaporthe oryzae and the bacterium Xanthomonas oryzae pv.oryzae(Xoo),respectively.Breeding rice varieties for broadspectrum resistance is considered the most effective and sustainable approach to controlling both diseases.Although dominant resistance genes have been extensively used in rice breeding and production,generating diseaseresistant varieties by altering susceptibility(S)genes that facilitate pathogen compatibility remains unexplored.Here,using CRISPR/Cas9 technology,we generated loss-of-function mutants of the S genes Pi21 and Bsr-d1 and showed that they had increased resistance to M.oryzae.We also generated a knockout mutant of the S gene Xa5 that showed increased resistance to Xoo.Remarkably,a triple mutant of all three S genes had significantly enhanced resistance to both M.oryzae and Xoo.Moreover,the triple mutant was comparable to the wild type in regard to key agronomic traits,including plant height,effective panicle number per plant,grain number per panicle,seed setting rate,and thousand-grain weight.These results demonstrate that the simultaneous editing of multiple S genes is a powerful strategy for generating new rice varieties with broadspectrum resistance.

Genetic Study Identifies CBLN4 as a Novel Susceptibility Gene for Accident Proneness

Frequent traffic accidents constitute a major danger to human beings.The accident-prone driver who has the stable physiological,psychological,and behavioral characteristics is one of the most prominent causes of traffic accidents.The internal link between the individual characteristics and the accident proneness has been a difficult point in the accident prevention research.The authors selected accident-prone drivers as cases and safe drivers as controls(case-control group) from 18,360 drivers who were enrolled from three public transportation incorporations of China using area stratified sampling method.The case-control groups were 1:1 matched.The authors performed genome-wide association study(GWAS) by 179 cases and 179 controls using the U.S.Affymetrix Genome-Wide Human Mapping SNP 6.0Array.The authors observed that the gene frequencies of34 single-nucleotide polymorphisms(SNPs) in three regions of cases were higher than those in the control(P < 10^(–4)).The authors then tested two independent replication sets for strong association 6 SNPs in 349 pairs of case-control drivers using the U.S.ABI 3730 sequencing method.The results indicated that SNP rs6069499 within linked CBLN4 gene are strongly associated with accident proneness(Pcombined= 6.37×10^(-10)).According to CBLN4 gene mainly involved in adrenal development and the regulation of secretion,the authors performed 12 biochemical parameters of the blood using radioimmunoassay.The levels of dopamine(DA) and adrenocorticotropic(ACTH)hormone showed significant differences between accidentprone drivers and safe drivers(P_(DA)= 0.03,P_(ACTH)= 0.01).It is suggested that the accident-prone drivers may have the idiosyncrasy of susceptibility.

Identification of Susceptibility Genes Loci Associated with Type 2 Diabetes

In this study, we selected 10 susceptible SNPs loci to investigate their contribution to susceptibility to type 2 diabetes in Hart Chinese among Hubei population. We genotyped SNPs rs5219, rs1801282, rs1470579, rs1111875, rs1081661, rs7754840, rs4506565, rs13266634, rs4402960, and rs5643981 by using the method of polymerase chain reaction-ligase detection reaction （PCR-LDR）. In a case-control study, we have genotyped the 10 candidate susceptibility SNP loci, and here, we reported that the SNP rs5219 in KCNJII was strongly associated with type 2 diabetes in Han Chinese in Hubei China There were significant differences in the TT genotype frequency （OR=1.6, 95%CI 1.1-2.3, p=0.01） and T allele frequency （OR=l.3, 95%C1 1.1-1.6, p-0.03） of SNP rs5219 between cases and controls. The other nine SNP loci did not show significant association with type 2 diabetes in Han Chinese in Hubei. The result suggests that KCNJ11 gene is a susceptibility gene of type 2 diabetes among this population.

The Alzheimer's disease-associated gene TREML2 modulates inflammation by regulating microglia polarization and NLRP3 inflammasome activation

Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

Differential expression analysis of coronary heart disease related genes in Hainan residents

Objective:To explore the correlation between coronary heart disease related genes and coronary heart disease in hospitalized patients in Hainan,and to provide theoretical basis for enriching the screening methods of high-risk groups of coronary heart disease in Hainan,and optimizing the prevention and treatment strategies.Methods:We select hospitalized patients born in Hainan and aged>30 years old from the Second Affiliated Hospital of Hainan Medical Unversity between January 1,2020 and June 30,2022,and divided the patients into the coronary heart disease group and the non-coronary heart disease group.PCR real-time fluorescence was used to measure gene expression,and Spearman correlation analysis was used to explore the correlation between gene expression and coronary heart disease.Results:A total of 55 whole blood samples were collected from non-coronary heart disease patients(including 26 women and 29 men),with a median age of 57 years,and 170 whole blood samples from coronary heart disease patients(including 44 women and 126 men),with a median age of 63.17.Apolipoprotein B gene(ApoB)was highly expressed in patients with coronary heart disease(P<0.001);AGT gene(P=0.0158),ApoE gene(P=0.0126),FGB gene(P=0.005),GNB gene(P=0.0151),MTFHR gene(P=0.0119),SEL gene(P=0.005),TNF gene(P=0.0298)were significantly overexpressed in the non-coronary heart disease group.The expression of NOS3 gene(P=0.3047),IL6 gene(P=0.7239),ACE gene(P=0.7852)was not different between the two groups.Coronary heart disease was negatively correlated with AGT gene(r=-0.163,P=0.011,P<0.05),positively correlated with APOB gene(r=0.75,P=0,P<0.01),negatively correlated with FGB gene(r=-0.163,P=0.011,P<0.05),negatively correlated with GNB gene(r=-0.165,P=0.011,P<0.05),negatively correlated withSEL gene(r=-0.171,P=0.007,P<0.01),negatively correlated with MHTHR gene(r=-0.210,P=0.001,P<0.01)and negatively correlated with TNF gene(r=-0.131,P=0.04,P<0.05),but coronary heart disease was not correlated with APOE,NOS3,ACE,IL6 and other genes(P>0.05).The ApoB gene of coronary heart disease was negatively correlated with triglyceride(r=-0.461,P=0),positively correlated with age(r=0.173,P=0.009),positively correlated with total cholesterol(r=0.499,P=0),negatively correlated with high-density lipoprotein(r=-0.181,P=0.007),and negatively correlated with low-density lipoprotein(r=-0.143,P=0.031).Conclusion:(1)The detection of apolipoprotein B gene expression may be used as an indicator for screening coronary heart disease in the coronary population in Hainan.It may increase the risk of coronary heart disease by affecting the level of total cholesterol.A larger sample of research is still needed.(2)AGT,ApoE,FGB,GNB,MTFHR,SELE,TNF and other genes may be the protective genes of non-coronary heart disease population in Hainan,and the high expression of these genes may reduce the occurrence of coronary heart disease,which still needs further study.

Engineering Broad-Spectrum Bacterial Blight Resistance by Simultaneously Disrupting Variable TALE-Binding Elements of Multiple Susceptibility Genes in Rice

Xanthomonas oryzae pv.oryzae(Xoo),the causal agent of bacterial blight of rice,employs the transcription activator-like effectors(TALEs)to induce the expression of the OsSWEET family of putative sugar transporter genes,which function in conferring disease susceptibility(S)in rice plants.To engineer broadspectrum bacterial blight resistance,we used CRISPR/Cas9-mediated gene editing to disrupt the TALEbinding elements(EBEs)of two S genes,OsSWEETH and OsSWEET14,in rice cv.Kitaake,which harbors the recessive resistance allele of Xa25/OsSWEET13.The engineered rice line MS14K exhibited broadspectrum resistance to most Xoo strains with a few exceptions,suggesting that the compatible strains may contain new TALEs.We identified two PthXo2-like TALEs,Tal5LN18 and Tal7PX061,as major virulence factors in the compatible Xoo strains LN18 and PX061,respectively,and found that Xoo encodes at least five types of PthXo2-like effectors.Given that PthXo2/PthXo2.1 target OsSlVEETf3 for transcriptional activation,the genomes of 3000 rice varieties were analyzed for EBE variationsin the OsSWEET13 promoter,and 10Xa25-like haplotypes were identified.We found that Tal5LN18 and Tal7PX〇6i bind slightly different EBE sequences in the OsSWEET13 promoter to activate its expression.CRISPR/Cas9 technology was then used to generate InDels in the EBE of the OsSWEET13 promoter in MS14K to creat a new germplasm with three edited OsSWEET EBEs and broad-spectrum resistance against all Xoo strains tested.Collectively,our findings illustrate how to disarm TALE-S co-evolved loci to generate broad-spectrum resistance through the loss of effector-triggered susceptibility in plants.

Fine mapping of susceptibility genes by Lewontin's linkage disequilibrium measure with application to Alzheimer's disease

Objectives To formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation. Methods Lewontin’s linkage disequilibrium (LD) measure D’ was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker (ε4 within the apolipoprotein E gene, APOE) and Alzheimer’s disease (AD) loci using published data.Results An equation was formulated for mapping disease genes under the above conditions. If these conditions are present but ignored, then recombination fraction θ between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of θ can be obtained. AD has been found to be associated with the marker allele ε4 in Africans, Asians, and Caucasians. This suggests that the AD-ε4 allelic LD predates the divergence of peoples occurring 100?000 years ago. With the age of AD-ε4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb). Conclusions (1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.

Bibliometric analysis of olaparib and pancreatic cancer from 2009 to 2022:A global perspective

BACKGROUND Genetic screening for breast cancer gene 1(BRCA)1/2 mutations can inform breast/ovarian/pancreatic cancer patients of suitable therapeutic interventions.Four to seven percent of pancreatic cancer patients have germline BRCA mutations.BRCA genes aid in DNA repair,especially homologous recombination,which impacts genomic stability and cancer cell growth.BRCA1 regulates the cell cycle,ubiquitination,and chromatin remodeling,whereas BRCA2 stimulates the immune response.They predict the efficacy of platinum chemotherapy or polymerase(PARP)inhibitors such as olaparib.AIM To determine the trends and future directions in the use of olaparib for pancreatic cancer treatment.METHODS To evaluate the trends in how olaparib works in pancreatic cancer,we performed a bibliometric analysis.One hundred and ninety-six related publications were accessed from the Web of Science Core Collection and were published between 2009 and 2022.The analytic parameters included publications,related citations,productive countries and institutes,influential authors,and keyword development.RESULTS This study visualizes and discusses the current research,including the present global trends and future directions in olaparib and pancreatic cancer.Overall,this study sheds light on optimizing the use of olaparib in pancreatic cancer treatment,Feng X et al.The use of olaparib in pancreatic cancer WJGO https://www.wjgnet.com 4490 November 15,2024 Volume 16 Issue 11 offering valuable guidance for researchers in this field.CONCLUSION Our findings identified trends in olaparib and pancreatic cancer,with China and the USA leading and with global cooperation tightening.O'Reilly EM's team and Memorial Sloan-Kettering had the highest output.The Journal of Clinical Oncology was the most cited journal.More PARP inhibitors are emerging,and combination therapy is suggested for future therapeutic trends.

Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.

Development of RAPD Markers and SCAR Markers Linked to Bentazon Susceptible Lethality Gene in Rice

Rice cultivar Norin 8 and its mutant Norin 8m harbour bentazon resistance trait and bentazon susceptibility trait respectively. A total of 360 arbitrary 10-mer oligonucleotide primers were screened on the genomic DNA of Norin 8 and Norin 8m with RAPD technique. Among which, five primers produced seven polymorphic RAPD bands between Norin 8 and Norin 8m. Amplified RAPD polymorphic products were cloned and sequenced. The sequences were used to design primers for PCR. Five SCAR markers, SCAR/G18/883, SCAR/G18/890, SCAR/G18/919/948, SCAR/D10/1237 and SCAR/F03/1186, were developed from OPG18/943, OPG18/972, OPD10/1248 and OPF03/1198. F-2 progeny of 320 individuals was analyzed to map SCAR markers in relationship to ben or Ben genes. SCAR markers of SCAR/G18/883, SCAR/G18/890, SCAR/G18/919/948 were shown to cosegregate with ben or Ben genes, and SCAR/D10/1237 to be linked of Ben gene with a distance of (14.8 +/- 2.1) cM. The genetic linkage to ben gene and SCAR markers was identified by a pair of near isogenic lines H121 and Hben121. Southern blotting analysis and segregation ratio of F-2 progeny revealed that OPG18/943 and OPG18/972 were single-copy in genome, and locus of OPG18/943 and OPG18/972 were allelic and sequence tagged sites. It is the first report on molecular markers linked to ben or Ben genes. The markers are useful to marker-assisted selection for the breeding and tag ben gene with map-based cloning.

Association of Graves’ disease and Graves’ ophthalmopathy with the polymorphisms in promoter and exon 1 of cytotoxic T lymphocyte associated antigen-4 gene

Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene. Methods: Thirty-three patients with ophthalmopathy of Graves’ disease, fifty-six Graves’ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Com-parisons were made of gene frequencies and allele frequencies between the groups. Results: The gene frequencies of CT and allele frequencies of T were much higher in Graves’ patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves’ disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves’ disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018). Conclusion: Our results suggest that an allele of T at position –318 of promoter is associated with genetic susceptibility to Graves’ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves’ disease instead. Smoking is believed to be a major risk factor for ophthalmo-pathy.

Genetic predisposition to pancreatic cancer

Pancreatic adenocarcinoma(PC) is the most deadly of the common cancers. Owing to its rapid progression and almost certain fatal outcome, identifying individuals at risk and detecting early lesions are crucial to improve outcome. Genetic risk factors are believed to play a major role. Approximately 10% of PC is estimated to have familial inheritance. Several germline mutations have been found to be involved in hereditary forms of PC, including both familial PC(FPC) and PC as one of the manifestations of a hereditary cancer syndrome or other hereditary conditions. Although most of the susceptibility genes for FPC have yet to be identified, next-generation sequencing studies are likely to provide important insights. The risk of PC in FPC is sufficiently high to recommend screening of high-risk individuals; thus, defining such individuals appropriately is the key. Candidate genes have been described and patients considered for screening programs under research protocols should first be tested for presence of germline mutations in the BRCA2, PALB2 and ATM genes. In specific PC populations, including in Italy, hereditary cancer predisposition genes such as CDKN2 A also explain a considerable fraction of FPC.

Can effectoromics and loss-of-susceptibility be exploited for improving Fusarium head blight resistance in wheat?

Bread wheat(Triticum aestiuum L.),which provides about 20%of daily calorie intake,is the most widely cultivated crop in the world,in terms of total area devoted to its cultivation.Therefore,even small increases in wheat yield can translate into large gains.Reducing the gap between actual and potential grain yield in wheat is a crucial task to feed the increasing world population.Fusarium head blight(FHB)caused by the pathogenic fungus Fusaium graminearum and related Fusarium species is one of the most devastating wheat diseases throughout the world.This disease reduces not only the yield but also the quality by contaminating the grain with mycotoxins harmful for humans,animals and the environment.In recent years,remarkable achievements attained in omics"technologies have not only provided new insights into understanding of processes involved in pathogenesis but also helped develop effective new tools for practical plant breeding.Sequencing of the genomes of various wheat patho gens,including F.graminearum,as well as those of bread and durum wheat and their wild relatives,together with advances made in transcriptomics and bioinformatics,has allowed the identification of candidate pathogen effectors and corresponding host resistance(R)and susceptibility(S)genes.However,so far,FHB effectors and wheat susceptibility genes/factors have been poorly studied.In this paper,we first briefly highlighted recent examples of improving resistance against pathogens via new techniques in different host species.We then propose effective strategies towards developing wheat cultivars with improved resistance to FHB.We hope that the article will spur discussions and interest among researchers about novel approaches with great potential for improving wheat against FHB.