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A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis

Chinese Medical Journal 2024年第4期137卷 431-440页

作者： Danyi Zou Yimin Cai Meng Jin Ming Zhang Yizhuo Liu Shuoni Chen Shuhui Yang Heng Zhang Xu Zhu Chaoqun Huang Ying Zhu Xiaoping Miao Yongchang Wei Xiaojun Yang Jianbo Tian Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Epidemiology and Biostatistics School of Public HealthTaiKang Center for Life and Medical SciencesWuhan UniversityWuhanHubei 430071China Department of Gastrointestinal Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430071China Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubei 430071China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Sciences and TechnologyWuhanHubei 430030China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)dataset.Then,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data.The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95%confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of ERAP1.The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.Conclusion:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.Trial Registration:No.NCT00454519(https://clinicaltrials.gov/)

关键词： Colorectal cancer Prognosis genetic variation Quantitative trait loci TCF3 rs71630754 Single nucleotide polymorphisms

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genetic variation at the p53 locus of two ecologically divergent Microtus pine voles:identification of molecular markers for species assignment

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Integrative Zoology 2022年第6期17卷 1179-1192页

作者： Ana Sofia QUINA João Paulo TAVANEZ Maria da Luz MATHIAS CESAM-Centro de Estudos do Ambiente e do Mar Departamento de BiologiaUniversidade de AveiroAveiroPortugal CESAM-Centro de Estudos do Ambiente e do Mar Faculdade de CiênciasUniversidade de LisboaLisboaPortugal Departamento de Biologia Animal Faculdade de CiênciasUniversidade de LisboaLisboaPortugal Global Health and Tropical Medicine(GHTM) Instituto de Higiene e Medicina Tropical(IHMT)Universidade NOVA de Lisboa(UNL)Portugal

The Lusitanian(Microtus lusitanicus)and the Mediterranean(Microtus duodecimcostatus)pine voles are recently diverged sister species endemic of the Iberian Peninsula that can be identiﬁed with ecological and morphological characters,but in areas where the 2 species co-occur,species designation may be difﬁcult.genetic discrimination between M.lusitanicus and M.duodecimcostatus has not been achieved yet possibly because of their estimated re-cent split and an evolutionary history that includes inter-species geneﬂow.Following our previous observations on exons 5–7 of the p53 gene,here we analyze the potential use of the p53 genomic region as a discrimination marker of these species by extending our analyses to several kb upstream and downstream of the p53 gene and charac-terizing the degree of genetic differentiation in 7 markers within this region.Additionally,we fully sequenced the P53 protein of both species.We observed:(i)generally high differentiation in this region;(ii)M.duodecimcostatus showed in general higher values of nucleotide and haplotype diversities;(iii)the concatenated phylogenetic tree separates the 2 species;(iv)the 2 P53 proteins only differ in 1 amino acid;(v)4 of the markers,2 in p53,one in Atp1b2,and another in Wrap53,contain species-speciﬁc genetic variation thus allowing a reliable discrimination between specimens from both species,irrespective of sampling location or introgression status.We provide ad-ditional data on the putative role of p53 in the evolution of these species and present researchers with a fast and cost-effective resource for M.lusitanicus and M.duodecimcostatus identiﬁcation.

关键词： ecological stress genetic variation Microtus molecular marker p53

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genetic variation and superior provenances selection for wood properties of Larix olgensis at four trials

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Journal of Forestry Research 2022年第6期33卷 1867-1879页

作者： Heng Zhang Shikai Zhang Shuopeng Chen Dean Xia Chuanping Yang Xiyang Zhao State Key Laboratory of Tree genetics and Breeding School of ForestryNortheast Forestry UniversityHarbin 150040People’s Republic of China

Larix olgensis,one of the most important timber species in northeastern China,is used for paper making and construction.In this study,10 wood properties(wood density,fiber length,fiber width,fiber length-to width ratio,hemicellulose content,cellulose content,holocellulose content,lignin content,ash content,and carbon content)of 10 provenances of L.olgensis planted at sites of CuoHai(CH),JiaGeDaQi(JGDQ),LiangShui(LS),and Mao'erShan(MES)were analyzed.The results of ANOVA showed that almost traits differed significantly among locations and provenances,with a significant interaction effect.Each trait also differed significant among provenances within sites.The phenotypic and genetic coefficient of variation(PCV and GCV)and provenance heritability(H 2)for wood properties ranged from 1.122 to 27.365%,from 0.564%to 21.113%and from 0.332 to 0.996,respectively.A correlation analysis showed that wood density was significantly negatively correlated with cellulose content and holocellulose content at sites CH,JGDQ,and LS,but were significantly positively correlated at site MES.Wood density was significantly negatively correlated with lignin content at CH and JGDQ,but not at LS and MES.Fiber width(FW)was negatively correlated with the ratio of fiber length(FL)to width across sites,and FW and FL/W were all positively correlated with FL.Lignin content was significantly positively correlated with hemicellulose content at site JGDQ and significantly negatively correlated with cellulose content and with holocellulose content at site MES.Interestingly,carbon content was positively correlated with cellulose content and holocellulose content at CH,but negatively correlated with these two traits at site MES.In a correlation analysis of wood properties with geographic,soil and climatic characteristics at the four sites,wood properties were mainly correlated with latitude and altitude of the site and affected by the average annual precipitation and temperature simultaneously.To select superior pulpwood provenances and high carbon storag

关键词： Larix olgensis Wood properties genetic variation Provenance selection Carbon content

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Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

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Cancer Biology & Medicine 2024年第6期21卷 473-483页

作者： Shuyi Chen Jing Gu Kaichun Wu Xiaodi Zhao Yuanyuan Lu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases Fourth Military Medical University School of Basic Medical Sciences Fourth Military Medical University

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

关键词： genetic variation gene amplification gene mutation gene rearrangement targeted therapy

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Insights into genetic variation and demographic history of sharpnose rays:examinations of three species of Telatrygon(Elasmobranchii,Dasyatidae)from the Indo-West Pacific

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Integrative Zoology 2022年第6期17卷 1063-1077页

作者： Jiwei QI Fanglei SHI Baowei ZHANG Xiao CHEN Jie XING Keisuke FURUMITSU Joel B.CORUSH Atsuko YAMAGUCHI Jie ZHANG Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijingChina School of Life Science Anhui UniversityHefeiAnhuiChina College of Marine Sciences South China Agricultural UniversityGuangzhouChina East China Sea Centre of Standard and Metrology SOAShanghaiChina Faculty of Fisheries Nagasaki UniversityNagasakiJapan Illinois Natural History Survey University of Illinois Champaign-UrbanaChampaignIllinoisUSA State Key Laboratory of Marine Resource Utilization in South China Sea Hainan UniversityHaikouChina

Coastal and demersal chondrichthyans(sharks,rays,and skates)are expected to exhibit high levels of genetic differentiation in areas of complex geomorphology.Population genetic studies investigating the extent to which demographic history shapes the genetic structure of theseﬁshes are rare.Here,we combined mitochondrial DNA(Cytb and ND2)and 8 nuclear microsatellite loci from 244 individuals to examine the population genetic structure and demographic history of the 3 Indo-West Paciﬁc species of sharpnose rays(Telatrygon zugei,Telatrygon biasa,and Trygon crozieri).High levels of genetic variation both within and between species were identiﬁed.Phylogenetic analysis partitioned haplotypes into 2 lineages supporting divergence of T.zugei from T.crozieri and T.biasa during the Pleistocene.Furthermore,microsatellite-based clustering analyses identiﬁed 4 genetic groups(i.e.T.zugei from Japan,T.zugei from coastal China,T.biasa from Gulf of Thailand,and T.crozieri from the Andaman Sea).Measurements of genetic differentiation also support these 4 groups.Additionally,Pleistocene demographic expansions were examined in all genetic groups.The climate oscillations and current hydrologic cycles in the Indo-West Paciﬁc appear to coincide with the hypothesis regarding speciation and the observed demographic history trends of the sharpnose rays.Considering the species group has,until recently,been thought to be one species,these results are critical for deﬁning management units and guiding conservation efforts to preserve stingray biodiversity.

关键词： conservation biodiversity of stingray demographic history genetic variation Indo-West Paciﬁc Telatrygon

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Genome-wide identification,evolutionary selection,and genetic variation of DNA methylation-related genes in Brassica rapa and Brassica oleracea

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Journal of Integrative Agriculture 2022年第6期21卷 1620-1632页

作者： AN Feng ZHANG Kang ZHANG Ling-kui LI Xing CHEN Shu-min WANG Hua-sen CHENG Feng Collaborative Innovation Center for Efficient and Green Production of Agriculture in Zhejiang Mountainous Areas College of Horticulture ScienceZhejiang A&F UniversityHangzhou 311300P.R.China Institute of Vegetables and Flowers Chinese Academy of Agricul tural SciencesBeijing 100081P.R.China

DNA methylation plays an important role in plant growth and development,and in regulating the activity of transposable elements(TEs).Research on DNA methylation-related(DMR)genes has been reported in Arabidopsis,but little research on DMR genes has been reported in Brassica rapa and Brassica oleracea,the genomes of which exhibit significant differences in TE content.In this study,we identified 78 and 77 DMR genes in Brassica rapa and Brassica oleracea,respectively.Detailed analysis revealed that the numbers of DMR genes in different DMR pathways varied in B.rapa and B.oleracea.The evolutionary selection pressure of DMR genes in B.rapa and B.oleracea was compared,and the DMR genes showed differential evolution between these two species.The nucleotide diversity(π)and selective sweep(Tajima’s D)revealed footprints of selection in the B.rapa and B.oleracea populations.Transcriptome analysis showed that most DMR genes exhibited similar expression characteristics in B.rapa and B.oleracea.This study dissects the evolutionary differences and genetic variations of the DMR genes in B.rapa and B.oleracea,and will provide valuable resources for future research on the divergent evolution of DNA methylation between B.rapa and B.oleracea.

关键词： DNA methylation Brassica rapa Brassica oleracea evolutionary selection genetic variation gene expression

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genetic variation of the 8-kDa glycoprotein family from Echinococcus granulosus, Taenia multiceps and Taenia hydatigena

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Chinese Medical Journal 2011年第18期124卷 2849-2856页

作者： JIA Wan-zhong YAN Hong-bin LOU Zhong-zi NI Xing-wei LIU Hong-xia LI Hong-min GUO Ai-jiang FU Bao-quan State Key Laboratory of Veterinary Etiological Biology KeyLaboratory of Veterinary Parasitology of Gansu Province KeyLaboratory of Veterinary Public Health of Ministry of AgricultureLanzhou Veterinary Research Institute Chinese Academy ofAgricultural Sciences Lanzhou Gansu 730046 China

Background Echinococcosis, coenurosis and cysticercosis are debilitating diseases which prevail in China. Immunological diagnosis of metacestodosis is important in disease control. The 8-kDa glycoproteins from taeniid cestodes have successfully been used for diagnosis of human cysticercosis in immunological assays. The aim of the present study was to investigate genetic variations and phylogenetic relationships of the 8-kDa proteins for evaluating the possibility of utilizing these proteins as diagnostic antigens for other metacestode infections. Methods The genes and complementary DNAs （cDNAs） encoding the 8-kDa proteins from Echinococcus （E.） granulosus, Taenia （T.） multiceps and T. hydatigena were amplified using PCR method. Their amplicons were cloned into the vector pMD18 and the positive clones were sequenced. Sequence data were analyzed with the SeqMan program, and sequence homology searches were performed using the BLAST program. Alignments were conducted using the ClustalX program, and the phylogenetic analyses were performed with the Protein Sequences Program and the Puzzle Program using the Neighbor-joining method. Results Fifteen, 18 and 22 different genomic DNA sequences were identified as members of the 8-kDa protein gene family from E. granulosus, T. multiceps and T. hydatigena, respectively. Eight, four and six different cDNA clones respectively from E. granulosus, T. multiceps and T. hydatigena were characterized. Analysis of these sequences revealed 54 unique 8-kDa protein sequences. Phylogenetic trees demonstrated that the taeniid 8-kDa proteins are clustered into eight clades at least： Ts18, Ts14, TsRS1, TsRS2, T8kDa-1, T8kDa-2, T8kDa-3 and T8kDa-4. Conclusion We found that the gene family encoding for the taeniid 8-kDa antigens is comprised of many members with high diversity, which will provide molecular evidence for cross-reaction or specific reaction among metacestode infections and may contribute to the development of promising immunological methods for diagnosis of metacestodosis.

关键词： Echinococcus granulosus Taenia multiceps Taenia hydatigena 8-kDa glycoprotein genetic variation

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The link between genetic variation and variability in vaccine responses:a narrative review

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Journal of Bio-X Research 2022年第2期5卷 49-54页

作者： Yingtian Zhang Mingzhe Zhao Wei Zhou Luan Chen Mo Li Bixuan Jiang Xianglong Zhao Hao Wu Lu Shen Na Zhang Hengwei Qin Yuhao Tang Chenhan Jiad Lin He Shengying Qin Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education) School of Life Sciences and Biotechnology Shanghai Jiao Tong University Institutes of Biomedical Sciences Fudan University School of Medicine Shanghai Jiao Tong UniversityShanghaiChina

Vaccines are one of the biggest successes in modern history and are particularly important in light of the multiple ongoing epidemics.Recently,vaccines have protected peoples’health and lives around the world during the coronavirus disease 2019 pandemic.Different types of vaccines have their own characteristics and advantages and are used in the context of different epidemics.Responses to vaccination are also different,and can include adverse reactions and absent responses.These individual differences are thought to be influenced by host genes.In this review,we first discuss vaccine types and characteristics.Second,we discuss different responses to vaccination,primarily focusing on the association between genetic variation and inter-individual differences.

关键词： adverse reaction genetic variation inter-individual difference review vaccine

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genetic variation of wood tracheid traits and their relationships with growth and wood density in clones of Pinus tabuliformis

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Journal of Forestry Research 2018年第4期29卷 1014-1023页

作者： Fangqun Ouyang Jianwei Ma Sanping An Junhui Wang Yuhui Weng State Key Laboratory of Tree genetics and Breeding Key Laboratory of Tree Breeding and Cultivation of State Forestry Administration Research Institute of Forestry Chinese Academy of Forestry Beijing 100083 People's Republic of China Research Institute of Forestry of Xiaolong Mountain Tianshui 741020 Gansu People's Republic of China Arthur Temple College of Forestry and Agriculture Stephen F. Austin State University Nacogdoches TX 75962 USA

To improve wood quality for pulpwood industries, it is important to examine not only wood density but also its components, especially tracheid characteristics. We studied genetic variations in the following tracheid traits by earlywood （EW） and latewood （LW）： tracheid length （TL）, double wall thickness （WT）, radial lumen diameter （R_D1）, tangential lumen diameter （T_D1）, radial central diameter （R_D2）, and tangential central diameter （T_D2）. We also studied the relationship with the following growth traits： diameter at breast height （DBH）, height （H）, crown breadth south-north axis （NSC）, crown breadth east-west axis （EWC）, ring width （RW）, latewood percentage （LWP）, and wood density （WD）. All sample materials were collected from a 33-year old clonal seed orchard of Pinus tabuliformis Carr. genetic variation among clones was moderate for all tracheid traits, 9.49-26.03%. Clones significantly affected WT, R_D1, R_D2, T_D1, T_D2, and the two ratios WT/R_D1 and TL/T_D2 in EW but had no effects in LW. Clones significantly affected TL in LW but had no effects in EW. H2/C was higher in LW （0.50） than in EW （0.20） for TL, while H 2/C was higher in EW （0.27-0.46） for other tracheid traits and the two ratios （TL/T_D2 and WT/R_D1） than in EW （0.06-0.22）. WD and TL were significantly positively correlated, but WT and TL were negatively correlated both at individual and clone levels; all tracheid diameters and the four ratio values （EW_WT/ R_D1, LW WT/R_D1, EW_TL/T_D2 and LW_TL/ T_D2）, were strongly positively correlated with DBH, H, NSC, WEC and RW, and strongly negatively correlated with WD both at individual and clone levels. The most important variables for predicting WD were LW_TL, EW_WT and R_D1 in both EW and LW （r2= 0.22）. Selecting the top 10% of the clones by DBH would improve DBH growth by 12.19% （wood density was reduced by 0.14%） and produced similar responses between EW and LW for all tracheid traits： a reduction of 0.94 and 3.69% in tracheid length and increases in tracheid diameters （from 0.36 to 5.24%） and d

关键词： Pinus tabuliformis Clone Tracheid traits Wood density genetic variation Correlation coefficient

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genetic variation of Laminaria japonica (Phaeophyta) populations in China as revealed by RAPD markers

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Acta Oceanologica Sinica 2011年第2期30卷 103-112页

作者： BI Yanhui HU Yuanjie ZHOU Zhigang Key Laboratory of genetic Resources and Ecology in Aquaculture Aquaculture E-Institute ofShanghai Municipal Education Committee Shanghai Ocean University Shanghai 201306 China

For the population genetics analysis of the naturally grown brown seaweed Laminaria japonica （Laminariales,Phaeophyta） sampled from Dalian,Yantai,Weihai,Rongcheng and Qingdao in China,ten primers were employed to produce 88 bands as revealed by randomly amplified polymorphic DNA （RAPD） markers,and all these bands were polymorphic.According to these band patterns,there were 94 distinct phenotypes occurred in 100 samples indicating the high heterozygosity of this kelp.Dalian population samples showed the highest percentage of polymorphism （71.67%）,and also the higher diversity estimated on the basis of the Shannon’s index （8.498）,suggesting that this population could be chosen as the best resource for genetic breeding.The highest diversity of Yantai population possibly resulted from the introduction of L.longissima used for interspecific cross breeding with L.japonica cultivated in China.From Dalian southwards to Qingdao,the genetic variation of the five populations became less with a decrease in latitude,possibly due to the natural selection especially of high temperature.The genetic distance （Φ ST values） of the five populations was a little significantly correlated with the geographical distance （r=0.496） at P =0.05 by Mantel’s test.Weihai,Rongcheng and Yantai populations were closely grouped genetically together by Neighbor-joining cluster analysis probably in that the dispersal of the kelp by propagules more easily occurring in the range of relatively short distance.The analysis of molecular variance （AMOVA） also demonstrated that the relatively higher variation occurred among populations （71.49%） at an extremely significant level （P 0.000 1）.All these evidence showed that there was a relatively distinct genetic differentiation among the sampled kelp populations,and L.japonica grown in China was also rather heterozygous in heredity.

关键词： AMOVA brown seaweed Laminaria japonica Aresch. population genetics RAPD genetic variation

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