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.

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.

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.

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.

AFLP Marker Linked to Turnip Mosaic Virus Susceptible Gene in Chinese Cabbage(Brassica rapa L.ssp.pekinensis)

Turnip mosaic virus (TuMV) which has several strains causes the most important virusdisease in Chinese cabbage in terms of crop damage. In China, Chinese cabbage is infectedby a mixture of strains, breeding of cultivar for the TuMV resistance has become themajor aim. Screening the molecular marker linked to the TuMV-resistance gene formolecular assisted selection is the major method to improve the breeding efficiency. Inthis study, we used AFLP technique and the method of bulked segregant analysis(BSA) tostudy the progeny of Brp0058Brp0108, and identified two DNA molecular marker linked toTurnip mosaic virus-resistance gene with a recombination frequency 7.5 cM and 8.4 cM.

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.

Polymorphism in cardiovascular diseases(CVD)susceptibility loci in the azores islands(Portugal)

Background: Atherosclerosis and thrombosis are the major manifestations underlying cardiovascular diseases (CVD), which are the leading cause of mortality and morbidity worldwide. Both result from an interaction between genetic and environmental risk factors. The goal of our study was to evaluate several polymorphisms identified as predisposing factors to atherosclerosis and thrombosis. Material and Methods: A series of 155 healthy unrelated individuals of Azorean origin were analyzed using the CVD StripAssay (ViennaLab Diagnostics, Austria) for the most established polymorphisms involved in blood coagulation (F2, F5, F13A1, FGB), fibrinolitic system (SERPINE1), platelet adhesion (ITGB3), homocysteine metabolism (MTHFR), reninangio-tensin system (ACE) and lipid metabolism (APOE). Results: No significant differences were observed in allelic frequencies when comparing our data to mainland Portugal. Group stratification according to the number of “increased” risk alleles, demonstrated that 116/155 (75%) individuals belong to the moderate risk group (5 - 10 risk alleles). Conclusions: Although acknowledging the fact that the allelic states at the analysed loci lack predictive value, the fact that a high frequency of individuals presents at least 5 risk alleles (124/155;80%) is important for the establishment of the appropriate preventive measures in the Azorean population.

淮北市听力筛查异常婴幼儿耳聋易感基因筛查特点分析

目的 分析淮北市听力筛查异常婴幼儿耳聋易感基因的特点,为婴幼儿耳聋防治工作的开展提供参考。方法选取2018年4月~2023年1月在淮北市妇幼保健院进行听力筛查的新生儿为研究对象,采用自动听性脑干诱发电位反应(AABR)和诊断性畸变产物耳声发射(DPOAE)进行复筛,对未通过AABR与DPOAE的婴幼儿进行遗传性聋相关基因检测(高通量测序法),包括GJB2、GJB3、SLC26A4和粒体12S rRNA,分析淮北市婴幼儿耳聋易感基因筛查特点。结果 共有67 150例婴幼儿进行听力筛查,初筛阳性率为12%,复筛阳性率为13.65%,未通过复筛者实施耳聋相关基因筛查,有84例检出常见遗传性聋基因突变位点,检出率为6.13%(84/1 100)。耳聋易感基因突变携带者听力损失发生率高于未携带者,差异有统计学意义(P<0.05)。4个常见遗传性聋基因中,以杂合突变最为常见。GJB2基因突变44例,以c.235delC位点突变为主;SLC26A4基因突变27例,以c.IVS7-2A>G位点突变为主;GJB3基因突变2例;线粒体12S rRNA 11例。GJB2基因与SLC26A4基因突变频率比较,GJB3基因与线粒体12S rRNA突变频率比较,差异均无统计学意义(P>0.05),GJB2基因和SLC26A4基因突变频率均高于GJB3基因突变和线粒体12S rRNA突变频率,差异有统计学意义(P<0.05)。结论 淮北市耳聋易感基因突变携带频率以GJB2基因c.235delC位点和SLC26A4基因c.IVS7-2A>G位点杂合突变最为常见,本地区耳聋基因筛查及遗传咨询工作开展过程中应着重注意GJB2基因与SLC26A4基因突变。

Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras signaling.Next,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls.Mechanistically,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC risk.In summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

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.

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.

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.

Association of HLA Alleles(A, B, DRB1) and HIV-1 Infection in the Han Population of Hubei, China

The HIV susceptibility and resistance alleles in the HLA genes were determined by investigating the distribution characteristics of the HLA alleles（A, B, and DRB1） in HIV-infected individuals of the Han population in Hubei, and by comparing these alleles with HIV-negative individuals from the same area. A cohort of 424 HIV-1 infected individuals were chosen as study subjects, and 836 HIV-negative healthy subjects from the same area served as the control population. HLA-A, B, and DRB1 allele typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probes（PCR-SSOP） and polymerase chain reaction-sequencing based typing（PCR-SBT） techniques. Arlequin ver3.0 was used to analyze the allele and haplotype frequencies of HLA-A, B, and DRB 1, whereas Epi Info 7 and SPSS18.0 was used to analyze the differences in the HLA alleles between the HIV-1 positive and HIV-1 negative groups. A＊02：03, DRB1＊01：01, and DRB1＊15：01 alleles and their haplotypes as well as the HLA_Bw4-Bw6 hybrid showed a protective effect on HIV-1 infection. After adjusting for confounding factors such as age and sex, multivariate logistic regression analysis revealed that B＊15：02G, DRB1＊01：01, and DRB1＊15：01 subtypes were the resistance genes of HIV-1 infection, while B＊13：01 might increase susceptibility to HIV-1 infection. The correlation between A＊02：06 and B＊15：01G subtypes and HIV-1 susceptibility was independent of the age and sex of the host. This study demonstrated the influence of genetic factors in humans such as HLA polymorphism on individuals to resist HIV-1 infection. Association studies of HLA polymorphism, susceptibility/resistance to HIV-1 infection, and hosts＇ genetic background are of significant importance for research on HIV-1 pathogenesis and vaccine design.

Plaque Psoriasis: Understanding Risk Factors of This Inflammatory Skin Pathology

Covering the entire human body, the skin is considered to be one of the most important organs, since it is the first line of protection against chemical and biological external agents. Although the skin protects tissues and organs against external aggression, it can still be unbalanced by various skin diseases, such as psoriasis. This non-contagious inflammatory dermatosis is characterized by the occurrence of erythematous lesions of various sizes covered with whitish scales. This scaling of the skin is the result of a rapid renewal of the epidermis, occurring over five to seven days instead of 28 days. Psoriasis vulgaris, or plaque psoriasis, is the most common form of this disease and is therefore commonly referred to by the term “psoriasis”. This work is a review of the literature on plaque psoriasis, aiming at a better comprehension of the pathology at the histological level, but also to understand the genetic and environmental factors associated with this inflammatory dermatosis.

Genetic mechanisms in generalized epilepsies

The genetic generalized epilepsies(GGEs)have been proved to generate from genetic impact by twin studies and family studies.The genetic mechanisms of generalized epilepsies are always updating over time.Although the genetics of GGE is complex,there are always new susceptibility genes coming up as well as copy number variations which can lead to important breakthroughs in exploring the problem.At the same time,the development of ClinGen fades out some of the candidate genes.This means we have to fgure out what accounts for a reliable gene for GGE,in another word,which gene has sufcient evidence for GGE.This will improve our understanding of the genetic mechanisms of GGE.In this review,important up-to-date genetic mechanisms of GGE were discussed.