基因变异命名规则

AbstractAnomenclaturesystemhasrecentlybeensug-gestedforthedescriptionofchanges(mutationsandpoly-morphisms)inDNAandproteinsequences.Thesenomenclaturerecommendationshavenowbeenlargelyaccepted.However,currentrulesdonotyetcoveralltypesofmutations,nordotheycovermorecomplexmu-tations.Thisdocumentliststheexistingrecommendationsandsummarizessuggestionsforthedescriptionofaddi-tional,morecomplexchanges.Anotherversionofthispa-perhasbeenpublishedinHumMut15:7–12,2000.IntroductionRecently,anomenclaturesystemhasbeensuggestedforthedescriptionofchanges(mutationsandpolymor-phisms)inDNAandproteinsequences(AntonarakisandtheNomenclatureWorkingGroup1998,).Thesenomenclaturerecommenda-tionshavenowbeenlargelyacceptedandstimulatedtheuniformandunequivocaldescriptionofsequencechanges.However,currentrulesdonotyetcoveralltypesofmuta-tions,nordotheycovermorecomplexmutations.Thisdocumentliststheexistingrecommendationsandsumma-rizessuggestionsforthedescriptionofadditionalandmorecomplexchanges(showninitalics)basedondenDunnenandAntonarakis(2000).Discussionsregardingtheadvantagesanddisadvan-tagesofthesuggestionsarenecessaryinordertocontinu-ouslyimprovethedesignationofsequencechanges.Theconsensusofthediscussionswillbepostedona(),andweinviteinvestigatorstocommunicatewithusregardingthesesug-gestions.Furthermore,weinviteinvestigatorstosenduscomplicatedcasesnotcoveredyet,withasuggestionofhowtodescribethese([e-mail]@medecine.unige.ch).Wehopethe“sequencevariation”isusedtopreventcon-fusionwiththeterms“mutation”and“polymorphism”,mutationmeaning“change”insomedisciplinesand“dis-ease-causingchange”inothersandpolymorphismmean-ing“non-disease-causingchange”or“changefoundatafrequencyof1%orhigherinthepopulation”.Thebasicrecommendationistousesystematicnamestodescribeeachsequencevariation.Forthis,variationsaredescribedatthemostbasiclevel,i.e.,theDNAlevel,usingeitheragenomicoracDNAreferencesequence.Agenomicreferencesequenceispreferredbecauseitover-comesdifficultcases,includingmultipletranscriptionini-tiationsites(promoters),alternativesplicing,theuseofdifferentpoly-Aadditionsignals,multipletranslationini-tiationsites(ATG-codons),andtheoccurrenceoflengthvariations.When,likeinmostcases,theentiregenomicsequenceisnotknown,acDNAreferencesequenceshouldbeusedinstead.Sequencevariationsaredescribedinrelationtoarefer-encesequenceforwhichtheaccessionnumberfromaprimarysequencedatabase(Genbank,EMBL,DDJB,SWISS-PROT)shouldbementionedinthepublica-tion/databasesubmission(e.g.,M18533)TabularlistingsofthesequencevariationsdescribedshouldcontaincolumnsforDNA,RNA,andproteinandclearlyindicatewhetherthechangeswereexperi-mentallydeterminedoronlytheoreticallydeducedJ.T.denDunnen·E.AntonarakisNomenclatureforthedescriptionofhumansequencevariationsHumGenet(2001)109:121–124DOI10.1007/s004390100505Received:12March2001/Accepted:13March2001/Publishedonline:19June2001NOMENCLATURERECOMMENDATIONSJ.T.denDunnenMGCDepartmentofHumanandClinicalGenetics,LeidenUniversityMedicalCenter,Leiden,TheNetherlandsS.E.Antonarakis(✉)DivisiondeGénétiqueMédicale,CentreMédicalUniversitaire,RueMichel-Servet1,1211Genève,Switzerlande-mail:[e-mail],Fax:[phone]©Springer-Verlag2001Toavoidconfusioninthedescriptionofasequencechange,preceedthedescriptionwithaletterindicatingthetypeofreferencesequenceused:“g.”foragenomicsequence(e.g.,g.76AT)“c.”foracDNAsequence(e.g.,c.76AT)“m.”foramitochondrialsequence(e.g.,m.76AT)“r.”foranRNAsequence(e.g.,r.76au)“p.”foraproteinsequence(e.g.,p.K76A)Todiscriminatebetweenthedifferentlevels(DNA,RNA,orprotein),descriptionsareunique:atDNA-level,incapitals,startingwithanumberreferingtothefirstnucleotideaffected(e.g.,c.76AT)atRNA-level,inlower-case,startingwithanumberreferingtothefirstnucleotideaffected(e.g.,r.76au)atproteinlevel,incapitals,startingwithaletterre-ferringtothefirstaminoacid(one-lettercode)af-fected(e.g.,p.T26P)Arangeofaffectedresiduesisindicatedbya“_”-character(underscore)separatingthefirstandlastresidueaffected(e.g.,76_78delACT)NOTE:currentrecommendationsusethe“–”-character(i.e.,76–78delACT)Fordeletionsorduplicationsinsinglenucleotide(oraminoacid)stretchesortandemrepeats,themost3’copyisarbitrarilyassignedtohavebeenchanged(i.e.ACTTTGTGCCtoACTTTGCCisdescribedas7_8delTG)Twosequencevariationsinoneallelearelistedbe-tweenbrackets,separatedbya“;”-character(e.g.,[76AC;83GC])NOTE:therecommendationsmadeindenDunnenandAntonarakis(2000)tousea“+”-characterasasepara-tor(i.e.,[76AC+83GC])hasbeenretractedSequencechangesindifferentalleles(e.g.,forreces-sivediseases)arelistedbetweenbrackets,separatedbya“+”-character(e.g.,[76AC]+[87delG])NOTE:thecurrentrecommendationis[76AC+87delG]Auniqueidentifiershouldbeassignedtoeachmuta-tion.TheuniqueOMI