突变表示方法.docx
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突变表示方法.docx
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突变表示方法
Nomenclatureforthedescriptionofsequencevariations
J.T.denDunnen,S.E.Antonarakis:
HumGenet109
(1):
121-124,2001
ReproducedwithkindpermissionfromProf.S.E.Antonarakis
(lastmodifiedMarch7,2001)
QuestionsandcommentsregardingnomenclatureshouldbedirectedtoProfessorStylianosAntonarakis( stylianos.antonarakis@medecine.unige.ch )orDr.JohanT.denDunnen( ddunnen@lumc.nl ).Thispagecanalsobefoundatthe HGVS site.
Contents
∙Introduction
∙Recommendations
oGeneral
oDNA-level
oRNA-level
oprotein-level
∙Codonsandencodedaminoacids
ogeneticcode
oaminoaciddescriptions (one/threelettercode)
Introduction
Recently,anomenclaturesystemhasbeensuggestedforthedescriptionofchanges(mutationsandpolymorphisms)inDNAandproteinsequences[Antonarakis,S.E.andtheNomenclatureWorkingGroup (1998) Recommendationsforanomenclaturesystemforhumangenemutations. Hum.Mut.11:
1-3].Thesenomenclaturerecommendationshavenowbeenlargelyacceptedandstimulatedtheuniformandunequivocaldescriptionofsequencechanges.However,currentrulesdonotyetcoveralltypesofmutations,nordotheycovermorecomplexmutations.Thisdocumentliststheexistingrecommendationsandsummarizessuggestionsforthedescriptionofadditional,morecomplexchanges,(showninitalics)basedonamanuscriptpublishedinHumanMutation[denDunnen,JTandAntonarakis,SE(2000). Mutationnomenclatureextensionsandsuggestionstodescribecomplexmutations:
adiscussion. Hum.Mut.15:
7-12](copyinPDFformat).
Discussionsregardingtheadvantagesanddisadvantagesofthesuggestionsarenecessaryinordertocontinuouslyimprovethedesignationofsequencechanges.Theconsensusofthediscussionswillbepostedhereandweinviteinvestigatorstocommunicatewithusregardingthesesuggestions.Furthermore,weinviteinvestigatorstosenduscomplicatedcasesnotcoveredyet,withasuggestionofhowtodescribethese(mailto ddunnen@lumc.nlandStylianos.Antonarakis@medecine.unige.ch).Wehopethesepageswillbeusedasaguidetodescribeanysequencechange,ultimatelyevolvingintoauniformlyacceptedreferenceformutationnomenclaturedescription.
Generalrecommendations
(suggestionsextendingthecurrentrecommendationsareinitaltics)
Theterm "sequencevariation" isusedtopreventconfusionwiththeterms "mutation" and "polymorphism",mutationmeaning"change"insomedisciplinesand"disease-causingchange"inothersandpolymorphismmeaning"nondisease-causingchange"or"changefoundatafrequencyof1%orhigherinthepopulation".
Thebasicrecommendationistouse systematicnames todescribeeachsequencevariation.Forthis,variationsaredescribedatthemostbasiclevel,i.e.theDNAlevel,usingeitheragenomicoracDNAreferencesequence.Agenomicreferencesequenceispreferredbecauseitovercomesdifficultcases,includingmultipletranscriptioninitiationsites(promoters),alternativesplicing,theuseofdifferentpoly-Aadditionsignals,multipletranslationinitiationsites(ATG-codons)andtheoccurenceoflengthvariations.When,likeinmostcases,theentiregenomicsequenceisnotknown,acDNAreferencesequenceshouldbeusedinstead.
∙sequencevariationsaredescribedinrelationtoareferencesequenceforwhichtheaccessionnumberfromaprimarysequencedatabase(Genbank,EMBL,DDJB,SWISS-PROT)shouldbementionedinthepublication/databasesubmission(e.g.M18533)
∙tabularlistingsofthesequencevariationsdescribedshouldcontaincolumnsforDNA,RNAandproteinandclearlyindicatewhetherthechangeswereexperimentallydetermined oronlytheoreticallydeduced
∙toavoidconfusioninthedescriptionofasequencechange,preceedthedescriptionwithaletterindicatingthetypeofreferencesequenceused;
o"g."fora genomic sequence(e.g.g.76A>T)
o"c."fora cDNA sequence(e.g.c.76A>T)
o"m."fora mitochondrial sequence(e.g.m.76A>T) (fromDavidFung,Camperdown,Australia)
o"r."foran RNA sequence(e.g.r.76a>u)
o"p."fora protein sequence(e.g.p.K76A)
∙todiscrimintatebetweenthedifferentlevels(DNA,RNAorprotein),descriptionsareunique;
oatDNA-level,incapitals,startingwithanumberreferingtothefirstnucleotideaffected(e.g.c.76A>T)
oatRNA-level,inlower-case,startingwithanumberreferingtothefirstnucleotideaffected(e.g.r.76a>u)
oatproteinlevel,incapitals,startingwithaletterreferringtofirsttheaminoacid(one-lettercode)affected(e.g.p.T26P)
∙arangeofaffectedresiduesisindicatedbya"_"-character(underscore)separatingthefirstandlastresidueaffected(e.g.76_78delACT)
NOTE:
currentrecommendationsusethe"-"-character(i.e.76-78delACT)
∙fordeletions,duplicationsorinsertionsinshorttandemrepeats,themost3'nucleotideisarbitrarilyassignedasthenucleotidechanged
∙twosequencevariationsinoneallelearelistedbetweenbrackets, separatedbya"+"-character (e.g.[76A>C+83G>C])
NOTE:
currentrecommendationsusethe";"-characterasaseparator(i.e.[76A>C;83G>C])
∙sequencechangesindifferentalleles(e.g.forrecessivediseases)arelistedbetweenbrackets,separatedbya"+"-character(e.g.[76A>C]+[87delG])
NOTE:
thecurrentrecommendationis[76A>C+87delG]
∙auniqueidentifiershouldbeassignedtoeachmutation.TheuniqueOMIM-identifiercanbeused,otherwisedatabasecuratorsshouldassignuniqueidentifiers
DNAlevel
∙nucleotidesaredesignatedbythebases(inuppercase);A(adenine),C(cytosine),G(guanine)andT(thymidine)
∙nucleotidenumbering;
onucleotide+1istheAoftheATG-translationinitiationcodon,thenucleotide5'to+1isnumbered-1;thereisnobase0
onon-codingregions;
▪thenucleotide5'oftheATG-translationinitiationcodonis-1
▪thenucleotide3'ofthetranslationterminationcodonis*1
ointronicnucleotides;
▪beginningoftheintron:
thenumberofthelastnucleotideofthepreceedingexon,aplussignandthepositionintheintron,e.g.77+1G,77+2T(whentheexonnumberisknown,thenotationcanalsobedescribedasIVS1+1G,IVS1+2T)
▪endoftheintron:
thenumberofthefirstnucleotideofthefollowingexon,aminussignandthepositionupstreamintheintron,e.g.78-2A,78-1G(whentheexonnumberisknown,thenotationcanalsobedescribedasIVS1-2A,IVS1-2G)
ofordeletions,duplicationsorinsertionsinsinglenucleotide(oraminoacid)stretchesortandemrepeats,themost3'copyisarbitrarilyassignedtohavebeenchanged(e.g.ACTTTGTGCCtoACTTTGCCisdescribedas7_8delTG)
Descriptionofnucleotidechanges
∙substitutions aredesignatedbya“>”-character
o76A>Cdenotesthatatnucleotide76aAischangedtoaC
o88+1G>T(alternativelyIVS2+1G>T)denotestheGtoTsubstitutionatnucleotide+1ofintron2,relativetothecDNApositionedbetweennucleotides88and89
o89-2A>C(alternativelyIVS2-2A>C)denotestheAtoCsubstitutionatnucleotide-2ofintron2,relativetothecDNApositionedbetweennucleotides88and89
NOTE:
polymorphicvariants aresometimesdescribedas76A/G,butthisisnotrecommened!
∙deletions aredesignatedby"del"afterthenucleotide(s)flankingthedeletionsite
o76_78del(alternatively76_78delACT)denotesaACTdeletionfromnucleotides76to78
o82_83del(alternatively82_83delTG)denotesaTGdeletioninthesequenceACTTTGTGCC(Aisnucleotide76)toACTTTGCC
oIVS2_IVS5del(alternatives88+?
_923+?
orEX3_5del)denotesanexonicdeletionstartingatanunknownpositioninintron2(afternucleotide88)andendingatanunknownpositioninintron5(afternucleotide923)
∙insertions aredesignatedby"ins"afterthenucleotidesflankingtheinsertionsite,followedbythenucleotidesinserted
NOTE:
asseparatorthe"^"-characterissometimesusedbutthisisnotrecommened(e.g.83^84insTG)
o76_77insTdenotesthataTwasinsertedbetweennucleotides76and77
o83_84insTGdenotesaTGinsertionintheTG-tandemrepeatsequenceofACTTTGTGCC(Aisnucleotide76)toACTTTGTGTGCC.Notethatthissequencevariation(aduplicatinginsertion)canalsobedescribedasaduplication,i.e.82_83dupTG(see"duplications")
∙variabilityofshortsequencerepeats,e.g.inACTGTGTGCC(Aisnt1991),aredesignatedas1993(TG)3-6withnucleotide1993containingthefirstTG-dinucleotidewhichisfoundrepeated3to6timesinthepopulation.
∙insertion/deletions(indels) aredescibedasadeletionfollowedbyaninsertionafterthenucleotidesafected
o112_117delinsTG(alternatively112_117delAGGTCAinsTGor112_117>TG)denotesthereplacementofnucleotides112to117(AGGTCA)byTG
∙duplications aredesignatedby"dup"afterthenucleotidesflankingtheduplicationsite,
o77_79dupCTGdenotesthatthenucleotides77to79wereduplicated
oduplicatinginsertionsinshorttandemrepeats(orsinglenucleotidestretches)canalsobedescribedasaduplication,e.g.aTGinsertionintheTG-tandemrepeatsequenceofACTTTGTGCC(Aisnt76)toACTTTGTGTGCCcanbedescribedas82_83dupTG(now83_84insTG)
∙inversions aredesignatedby"inv"afterthenucleotidesflankingtheinversionsite
o203_506inv(or203_506inv304)denotesthatthe304nucleotidesfromposition203to506havebeeninverted
∙translocations (nosuggestionsyet)
∙changesindifferentalleles (e.g.inrecessivediseases)aredescribedas"[changeallele1]+[changeallele2]"
o[76A>C]+[76A>C]denotesahomozygousAtoCchangeatnucleotide76
o[76A>C]+[?
]denotesaAtoCchangeatnucleotide76inonealleleandanunknownchangeintheotherallele
∙twovariationsinoneallele aredescribedas"[firstchange+secondchange]"
o[76A>C+83G>C]denotesanAtoCchangeatnucleotide76andaGtoCchangeatnucleotide83inthesameallele
NOTE:
currentrecommendationsuse
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