突变表示方法.docx

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]denotesanAtoCchangeatnucleotide76andaGtoCchangeatnucleotide83inthes