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简介：Shorttandemrepeats(STRs)areshorttandemlyrepeatedDNAsequencesthatinvolvearepetitiveunitof1–6bp.Becauseoftheirpolymorphismsandhighmuta-tionrates,STRsarewidelyusedinbiologicalresearch.Strand-slippagereplicationisthepredominantmutationmechanismofSTRs,andthestepwisemutationmodelisregardedasthemainmutationmodel.STRmutationratescanbeinfluencedbymanyfactors.Moreover,sometrinucleotiderepeatsareassociatedwithhumanneurodegenerativediseases.InordertodeepenourknowledgeofthesediseasesandbroadenSTRapplication,itisessentialtounderstandtheSTRmutationpro-cessindetail.Inthisreview,wefocusonthecurrentknowninformationaboutSTRmutation.

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简介：Electrophoresis,chromatography,immunoassay,sequencingandothertimeconsumingap-proacheshavebeendevelopedtodetermineDNAbasemismatching,oxidativelesionorstrandbreaks.Sometimes,however,onlyqualitativeinformationisenoughtodecidewhethermutationhashappenedtoDNAanditsextent.Convolutionspectrometry(CS),anewtechniquetodiscoverultrafmedifferenceonultraviolet(UV)absorptionofdifferentsubstances,isoriginallyemployedtofindoutanysubtlemutationofDNAinducedbyUVradiation.Muta-tiveDNAiscomparedwithegocriteriabasedonthespectraoftheformerDNA,anydifferenceisquantitativelyex-pressedbydispersion(5).Visiblechangescannotbeobservedonsecond-derivativespectrauntilthemutationgets5upto11.48%.DimethylsulfoxideisanintensifierofUV254nminducedDNAmutationandprotectorat365nm,whichissimplyconfirmedbyincreasinganddecreasing5.Everyconvolutionproceduretakeslessthan1min.Convolutionspectrometryprovidesafast,simple,sensitiveandinexpensivealternativetodetermineDNAmutation,andtoscreenanti-mutationalmedicines.

简介：Lungcancerisacommonmalignanttumor,whichhasahighincidenceandmortalityrate.Therefore,itisnecessarytoseekanewmethodforthediagnosis,especiallytheearlydiagnosisoflungcancer.Thedevelopmentofmolecularbiologymakesthegenediagnosisoflungcancerpossible.PCR-SSCP...

简介：Objective:Signetringcellcarcinomaisararesubtypeofcolorectalcarcinoma(CRC)withanassociatedBRAFV600Emutation.WeinvestigatedfrequenciesofBRAFmutationin28CRCscontainingvariablesignetringcellcomponentandtheirrelationwithclinicopathologicparameters.Methods:Accordingtothepresenceofsignetringcellcomponent,tumorswerecategorizedintogroupsasfollows:0%–9%,10%–24%,25%–49%,and>50%.GenomicDNAwasisolatedandanalyzedforBRAFV600Egenemutationbypolymerasechainreaction-restrictionfragmentlengthpolymorphism.Elevenof28cases(39.3%)showedBRAFV600Emutation,whichwasalsoconfirmedbySangersequencing.Toelucidatetheimportanceofexistenceofsignetringcellcomponentatthemolecularlevel,weseparatedcasesintotwogroupswithcut-offlevelsof10%and50%,whichpertaintopercentagesofsignetringcells.Results:Sevenof19cases(36.8%)underthethresholdof50%andfourofninecases(44.4%)overthisthresholdvaluedemonstratedBRAFmutation.Threeof7cases(42.8%)featuring<10%signetringcellcomponentandeightoutof21cases(38.1%)showing>10%wereBRAFmutated.Conclusions:BRAFmutationmustbecloselyassociatedwiththepresenceofmalignantsignetringcellsregardlessoftheirpercentages.

简介：Cowdensyndrome(CS),anautosomaldominantdisorder,isoneofaspectrumofclinicaldisordersthathavebeenlinkedtogermlinemutationsinthephosphataseandtensinhomolog(PTEN)gene.Although70-80%ofpatientswithCShaveanidentifiablegermlinePTENmutation,theclinicaldiagnosispresentsmanychallengesbecauseofthephenotypicandgenotypicvariations.Inthepresentstudy,wesequencedtheexonsandthepromoterofPTENgene,mutationsandvariationsinthepromoterandexonswereidentified,andaPTENproteinexpressionnegativeregionwasdeterminedbyimmunohistochemistry(IHC).Inconclusion,anovelpromotermutationwefoundinPTENgenemayturnoffPTENproteinexpressionoccasionally,leadingtothedisorderofPTENanduntypicalCSmanifestations.

简介：Objective:Toinvestigatetherelationshipbetweengenemutationandpathologicaltypeoflungcancer,inspectandverifytheconsistencybetweenhomologousgenesmutationinvariouspathologictype.Methods:CombinedwiththeCOSMICandUniProtdatabase,weobtainedthereportedoverallbig-samplemutationdataoflungcancerandtheproteinsequencesofthetop20mutatedgenes,respectively.Analyzethedataandclustertheproteinsequencesandthendeducethehomologousgene.Ultimately,analyzethemutationsofdifferentpathologicaltypesofhomologousgenes.Results:TP53(32.32%)hasthehighestmutationrateinlungcancer,followedbyEGFR(29.12%).Thecopynumbervariability(CNV)ofgenes:KRAS,LRP1B,CDKN2A,KMT2C,FAT1,PIK3CA,RB1,ERBB4,GRIN2AandKDRbetweeneachpathologicaltypeisstaticallysignificant(P<0.05).ThegenedifferentialexpressionratebetweenadenocarcinomaandsquamouscarcinomaofgeneTP53,KRAS,LRP1B,CDKN2A,STK11,FAT4,KMT2D,NFE2L2,KEAP1,PIK3CA,RB1,ERBB4,SMARCA4andKDRarestatisticallysignificant(P<0.05).ThesimilarityoftheproteinsequenceofEGFRandERBB4canreach93%,andFAT4andFAT1are81%.Forsmallcellcarcinoma,there’snodifferenceinCNVbetweenthetwogroupsofhomologousgenes,andnodifferencebetweenFAT4andFAT1inadenocarcinoma.Conclusion:TheCNVandgeneexpressionoflungcancer-associatedgenesarerelevanttopathologictypes.GFRandERBB4arehomologous,FAT4andFAT1arealsoamongthetop20mutationgenes.Additionally,there’snodifferenceinCNVbetweenthetwogroupsofsmallcellcarcinoma,whichisthesamebetweenFAT4andFAT1inadenocarcinoma.

简介：Lowtemperatureairplasmawasusedasthemutationtoolforpenicillin-producingstrainPenicilliumchrysogenum.ThedischargeconditionswereRFpowerof360W,temperatureof40℃inasealedchamber,andpressureof10Pato30Pa.Theresultshowedthatthekineticsofthesurvivalratefollowedatypicalsaddle-shapedcurve.Basedonastatisticanalysis,atthetreatingdurationof10min,thepositivemutationratewasashighas37.5%whilethenegativemutationratewaslow.Thecolonialmorphologychangedobviouslywhentheplasmatreatingdurationreachedorexceeded45min.Afterbothprimaryandsecondaryscreening,amutantdesignatedasaPc051310withhighproductivityofpenicillinwasobtained,andastrongmutageniceffectonP.chrysogenumwasobservedintheprocess.Itwasprovedthatafterfivegenerations,themutantaPc051310stillexhibitsahighproductivity.Alltheresultsprovethattheplasmamutationmethodcouldbedevelopedasaconvenientandeffectivetooltobreedhigh-yieldstrainsinthefermentationindustry,whileexpandingtheplasmapplicationatthesametime.

简介：DNAcompositiondynamicsacrossgenomesofdiversetaxonomyisamajorsubjectofgenomeanalyses.DNAcompositionchangesarecharacteristicsofbothreplicationandrepairmachineries.Weinvestigated3,611,007singlenucleotidepolymorphisms(SNPs)generatedbycomparingtwosequencedricegenomesfromdistantinbredlines(subspecies),includingthosefrom242,811intronsand45,462protein-codingsequences(CDSs).Neighboring-nucleotideeffects(NNEs)oftheseSNPsarediverse,dependingonstructuralcontent-basedclassifications(genomewide,intronic,andCDS)andsequencecontext-basedcategories(A/C,A/G,A/T,C/G,C/T,andG/Tsubstitutions)oftheanalyzedSNPs.StrongandevidentNNEsandnucleotideproportionbiasessurroundingtheanalyzedSNPswereobservedin1-3bpsequencesonbothsidesofanSNP.Strongbiaseswereobservedaroundneighboringnucleotidesofprotein-codingSNPs,whichexhibitaperiodicityofthreeinnucleotidecontent,constrainedbyacombinedeffectofcodon-relatedrulesandDNArepairmechanisms.Unlikeapreviousfindinginthehumangenome,wefoundnegativecorrelationbetweenGCcontentsofchromosomesandthemagnitudeofcorrespondingbiasofnucleotideCat-1siteandGat+1site.Theseresultswillfurtherourunderstandingofthemutationmechanisminriceaswellasitsevolutionaryimplications.

简介：Byusingageneralizedfitness-dependentMoranprocess,anevolutionarymodelforsymmetric2×2gamesinawell-mixedpopulationwithafinitesizeisinvestigated.Inthemodel,theindividuals’payoffaccumulatingfromgamesismappedintofitnessusinganexponentfunction.Bothselectionstrengthβandmutationrateεareconsidered.Theprocessisanergodicbirth-deathprocess.Basedonthelimitdistributionoftheprocess,wegivetheanalysisresultsforwhichstrategywillbefavouredwhenεissmallenough.Theresultsdependonnotonlythepayoffmatrixofthegame,butalsoonthepopulationsize.Especially,weprovethatnaturalselectionfavoursthestrategywhichisrisk-dominantwhenthepopulationsizeislargeenough.Forarbitraryβandεvalues,the’Hawk-Dove’gameandthe’Coordinate’gameareusedtoillustrateourmodel.Wegivetheevolutionarystablestrategy(ESS)ofthegamesandcomparetheresultswiththoseofthereplicatordynamicsintheinfinitepopulation.Theresultsaredeterminedbysimulationexperiments.

简介：Heavyionbeamsaregenerallyrecognizedasoneofpowerfulmutagensinplantbreedingtogeneratenewmutantswithidealorusefulagronomiccharacters[1].12C6+ionbeams(80MeV/u)acceleratedbyHeavyIonResearchFacilityinLanzhou(HIRFL)wereusedtoirradiatewheatsamples,oneofthemajorwheatvarietiesinQinghaiprovince,namedGaoyuan448.Theradiationdosesrangedfrom10to200Gy.Theirradiatedsamples,controls,andanothermajorwheatvarietynamedAbowereplantedinfarmlocatinginLeducountyofQinghaiprovincein2014.

简介：AbstractImportance:Infantile convulsions and choreoathetosis (ICCA) is a rare neurological disorder. Many affected patients are either misdiagnosed or prescribed multiple antiepileptic drugs.Objective:To explore therapeutic drug treatments and dosages for ICCA in children.Methods:Detailed clinical features (e.g., past medical history and family history), genetic features, and treatment outcomes were collected from the records of six patients with ICCA.Results:Mean age at paroxysmal kinesigenic dyskinesia (PKD) onset was 8 years 8 months (range, 3-12 years); the clinical presentation was characterized by daily short paroxysmal episodes of dystonia/dyskinesia. All patients had infantile convulsions at less than 1 year of age, and the mean onset age was 5.5 months (range, 4-7 months). Two patients had a family history of ICCA, PKD, or benign familial infantile epilepsy. Whole exome sequencing identified the c.649-650insC mutation in PRRT2 in six patients; three mutations were inherited and three were de novo. All patients were prescribed low-dose carbamazepine and showed dramatic improvement with the complete disappearance of dyskinetic episodes after 3 days. They attended follow-up for 5-17 months and were attack-free until the final follow-up.Interpretation:PRRT2 mutations are the primary cause of ICCA. Low-dose carbamazepine monotherapy is effective and well-tolerated in children.

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简介：ObjectivesPhenotypicoverlapofBrugadasyndromewithtype3longQTsyndromeisobservedinsomecarriersofmutationsintheNachannelSCN5A.Concomitant-Brugadasyndromeand3typelongQTsyndromeassociatedwithsodiumchannelmutationwasreportedbefore,however,nodatashowedconcomitant-BrugadatypeandshortQTintervalelectrocardiogram(ECG)andrevealedtheassociated-genemutation.MethodsThedirectDNAsequencewasconducedtofindthemutation.Themutationwasreproducedinvitrousingsite-directedmutagenesisandcharacterizedusingthepatchclamptechniqueinthewhole-cellconfiguration.ResultsThepatientwiththefamilyhistoryofsuddendeathshowedBrugadaandshortQTintervalECG.SequenceofSCN5Aidentifiedamissensemutation,R689H,previouslyassociatedwithalongQTsyndrome.BiophysicalstudyshowedthattheR689Hfailedtogenerateanycurrentwhenheterolo-gouslyexpressedinHEKcells.ConclusionsOurfindingsindicateforthefirsttimethatcoexisted-BrugadatypeandshortQTintervalECGlinkedtothelossoffunctioninSCN5Amutation.

简介：AbstractObjective:The purpose of this study was to examine the role of rare variants in the one-carbon metabolic pathway in the etiology of the cerebral folate deficiency (CFD) syndrome. The CFD syndrome is a neurometabolic syndrome identified by low concentrations of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF) in spite of near-normal peripheral folate levels resulting in neurodevelopmental disorders.Methods:The localized folate metabolism impairments in CFD are thought to be either the result of mutations in genes responsible for folate transport or folate turnover through degradation. Genes that have been previously implicated in the etiology of CFD include folate receptor alpha-1 (FOLR1), dihydrofolate reductase, proton-coupled folate transporter, and capicua. We performed whole-exome sequencing (WES) analysis of a CFD patient that revealed 99 novel missense mutations, of which 21 were classified as damaging mutations through the Poly-Phen2 prediction algorithm. In vitro functional studies were conducted by transient transfection of wild-type and mutant MTHFS into HEK293T cells to determine the impact of the variants on enzyme activity.Results:Of the damaging variants identified in the WES studies, we focused on the gene coding for the enzyme 5,10-methenyl-tetrahydrofolate synthetase (MTHFS). This enzyme catalyzes the production of methenyl THF which is subsequently converted to 5-MTHF. The CFD patient described within was found to carry a homozygous mutation, c.101G>T (p.R34L, rs200058464) in MTHFS, while the parents of the proband are heterozygotes for the MTHFS gene, and the healthy sibling is not a carrier.Conclusion:The mutant allele displayed a 50% reduction in luciferase activity (P < 0.05), suggesting that homozygous loss of the MTHFS gene may play a significant role in the development of CFD.

简介：AbstractObjectives:Hearing loss is a worldwide disease. In 50% of the patients, hearing loss is caused by genetic problems associated with GJB2, MTRNR1, SLC26A4, and other genes. Considering the recent development and cost reduction of whole-exome sequencing, it is possible to filter out the normal genes and find which among the more novel genes contributed to the loss of hearing.Methods:After prescreening all individuals for GJB2, MTRNR1 and SLC26A4 mutations, whole-exome sequencing was performed in the proband, and the pathogenic variant was confirmed via Sanger sequencing.Results:The compound-heterozygous variant namely c.8076G>C:p.E2692D and c.6362T>C:p.V2121A in OTOG was identified as a candidate gene of a consanguineous Kazakh family.Conclusion:This is the first reported case of severe deafness caused by an OTOG compound-heterozygous variant in the world and the first case of deafness caused by an OTOG variant in China. This discovery identified the important contribution of OTOG toward deafness and expanded the spectrum of variants responsible for human hearing loss.

简介：MutationsinGJB2genearethemostfrequentlyfoundmutationsinpatientswithnonsyndromichearingimpairment.However,thespectrumandprevalenceofmutationsinthisgenevaryamongdifferentethnicgroups.InChina,30,000infantsarebornwithcongenitalhearingimpairmentannually.Inordertoprovideappropriategenetictestingandcounselingtothefamilies,weinvestigatedthemolecularetiologyofnonsyndromicdeafnessin103unrelatedschoolchildrenattendingNantongSchoolfortheDeafandMuteinJiangsuProvince,China.ThecodingexonoftheGJB2genewasPCRamplifiedandsequenced.SixtytwoGJB2mutantalleleswereidentifiedin35.9%(37/103)ofthepatients.Twentyfivepatientscarriedtwopathogenicmutationsand12patientscarriedonemutantallele.The235delCwasthemostcommonmutationaccountingfor69.4%(43/62)ofGJB2mutantalleles.TheGJB2mutantallelesaccountedfor30.1%(62/206)ofallchromosomesresponsiblefornonsyndromichearingimpairment.Testingofthe3mostprevalentdeleteriousframeshiftmutationsinthiscohortdetected100%ofallGJB2mutantalleles.TheseresultsdemonstratethataneffectivegenetictestingofGJB2geneforpatientsandfamilieswithnonsyndromichearingimpairmentispossible.

简介：ObjectiveThestudyistoidentifythecarrierrateofcommondeafnessmutationinChinesepregnantwomenviadetectingdeafnessgenemutationswithgenechip.MethodsThepregnantwomeninobstetricclinicwithouthearingimpairmentandhearingdisordersfamilyhistorywereselected.Theinformedconsentwassigned.PeripheralbloodwastakentoextractgenomicDNA.Applicationofgeneticdeafnessgenechipfordetecting9mutationalhotspotofthemostcommon4Chinesedeafnessgenes,namelyGJB2(35delG,176del16bp,235delC,299delAT),GJB3(C538T),SLC26A4(IVS72A>G,A2168G)andmitochondrialDNA12SrRNA(A1555G,C1494T).Furthergenetictestingwereprovidedtothespousesandnewbornsofthescreenedcarriers.ResultsPeripheralbloodof430pregnantwomenweredetected,detectionofdeafnessgenemutationcarriersin24cases(4.2%),including13casesoftheGJB2heterozygousmutation,3casesofSLC26A4heterozygousmutation,1casesofGJB3heterozygousmutation,and1caseofmitochondrial12SrRNAmutation.18spousesand17newbornstookfurthergenetictests,and6newbornsinheritedthemutationfromtheirmother.ConclusionThecommondeafnessgenesmutationhasahighcarrierrateinpregnantwomengroup,235delCandIVS7-2A>Gheterozygousmutationsarecommon.