突变命名规范.docx
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突变命名规范.docx
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突变命名规范
突变命名规范
Nomenclatureforthedescriptionofsequence
variations
J.T.denDunnen,S.E.Antonarakis:
HumGenet109
(1):
121-124,2001
ReproducedwithkindpermissionfromProf.S.E.
Antonarakis
(lastmodifiedMarch7,2001)
Questionsandcommentsregardingnomenclatureshouldbedirectedto
ProfessorStylianosAntonarakis(stylianos.antonarakis@medecine.unige.ch
)orDr.JohanT.denDunnen(ddunnen@lumc.nl
).ThispagecanalsobefoundattheHGVSsite.ContentsIntroduction
Recommendations
General
DNA-level
RNA-level
protein-level
Codonsandencodedaminoacids
geneticcode
aminoacid
descriptions(one/threelettercode)IntroductionRecently,anomenclaturesystemhasbeensuggestedforthedescriptionof
changes(mutationsandpolymorphisms)inDNAandproteinsequences[Antonarakis,
S.E.andtheNomenclatureWorkingGroup(1998)Recommendationsfora
nomenclaturesystemforhumangenemutations.Hum.Mut.11:
1-3].Thesenomenclature
recommendationshavenowbeenlargelyacceptedandstimulatedtheuniformand
unequivocaldescriptionofsequencechanges.However,currentrulesdonotyet
coveralltypesofmutations,nordotheycovermorecomplexmutations.This
documentliststheexistingrecommendationsandsummarizessuggestionsforthe
descriptionofadditional,morecomplexchanges,(showninitalics)
basedonamanuscriptpublishedinHumanMutation[denDunnen,JTandAntonarakis,
SE(2000).Mutationnomenclature
extensionsandsuggestionstodescribecomplexmutations:
adiscussion.Hum.Mut.15:
7-12](copyinPDF
format).
Discussionsregardingtheadvantagesanddisadvantagesofthesuggestions
arenecessaryinordertocontinuouslyimprovethedesignationofsequence
changes.Theconsensusofthediscussionswillbepostedhereandweinvite
investigatorstocommunicatewithusregardingthesesuggestions.Furthermore,
weinviteinvestigatorstosenduscomplicatedcasesnotcoveredyet,witha
suggestionofhowtodescribethese(mailtoddunnen@lumc.nlandStylianos.Antonarakis@medecine.unige.ch).
Wehopethesepageswillbeusedasaguidetodescribeanysequencechange,
ultimatelyevolvingintoauniformlyacceptedreferenceformutation
nomenclaturedescription.Generalrecommendations
(suggestionsextendingthecurrentrecommendationsareinitaltics)Theterm"sequencevariation"isusedtoprevent
confusionwiththeterms"mutation"and"polymorphism",
mutationmeaning"change"insomedisciplinesand
"disease-causingchange"inothersandpolymorphismmeaning"non
disease-causingchange"or"changefoundatafrequencyof1%or
higherinthepopulation".
Thebasicrecommendationistousesystematicnamesto
describeeachsequencevariation.Forthis,variationsaredescribedatthe
mostbasiclevel,i.e.theDNAlevel,usingeitheragenomicoracDNA
referencesequence.Agenomicreferencesequenceispreferredbecauseit
overcomesdifficultcases,includingmultipletranscriptioninitiationsites
(promoters),alternativesplicing,theuseofdifferentpoly-Aaddition
signals,multipletranslationinitiationsites(ATG-codons)andtheoccurence
oflengthvariations.When,likeinmostcases,theentiregenomicsequenceis
notknown,acDNAreferencesequenceshouldbeusedinstead.
sequence
variationsaredescribedinrelationtoareferencesequenceforwhichthe
accessionnumberfromaprimarysequencedatabase(Genbank,EMBL,DDJB,
SWISS-PROT)shouldbementionedinthepublication/databasesubmission
(e.g.M18533)
tabular
listingsofthesequencevariationsdescribedshouldcontaincolumnsfor
DNA,RNAandproteinandclearlyindicatewhetherthechangeswereexperimentally
determinedoronlytheoreticallydeduced
toavoid
confusioninthedescriptionofasequencechange,preceedthedescription
withaletterindicatingthetypeofreferencesequenceused;
"g."
foragenomicsequence(e.g.g.76A>T)
"c."
foracDNAsequence(e.g.c.76A>T)
"m."
foramitochondrialsequence(e.g.m.76A>T)(fromDavidFung,Camperdown,Australia)
"r."
foranRNAsequence(e.g.r.76a>u)
"p."
foraproteinsequence(e.g.p.K76A)
to
discrimintatebetweenthedifferentlevels(DNA,RNAorprotein),
descriptionsareunique;
at
DNA-level,incapitals,startingwithanumberreferingtothefirst
nucleotideaffected(e.g.c.76A>T)
at
RNA-level,inlower-case,startingwithanumberreferingtothefirst
nucleotideaffected(e.g.r.76a>u)
atprotein
level,incapitals,startingwithaletterreferringtofirsttheamino
acid(one-lettercode)affected(e.g.p.T26P)
arangeof
affectedresiduesisindicatedbya"_"-character(underscore)
separatingthefirstandlastresidueaffected(e.g.76_78delACT)
NOTE:
currentrecommendationsuse
the"-"-character(i.e.76-78delACT)
for
deletions,duplicationsorinsertionsinshorttandemrepeats,themost3'
nucleotideisarbitrarilyassignedasthenucleotidechanged
twosequencevariationsinoneallelearelistedbetweenbrackets,separated
bya"+"-character(e.g.[76A>C+83G>C])
NOTE:
currentrecommendationsusethe";"-characterasa
separator(i.e.[76A>C;
83G>C])
sequence
changesindifferentalleles(e.g.forrecessivediseases)arelisted
betweenbrackets,separatedbya"+"-character(e.g.[76A>C]+[87delG])
NOTE:
thecurrentrecommendationis[76A>C+87delG]
aunique
identifiershouldbeassignedtoeachmutation.TheuniqueOMIM-identifier
canbeused,otherwisedatabasecuratorsshouldassignuniqueidentifiersDNAlevelnucleotidesaredesignated
bythebases(inuppercase);A(adenine),C(cytosine),G(guanine)andT
(thymidine)
nucleotidenumbering;
nucleotide+1istheAof
theATG-translationinitiationcodon,thenucleotide5'to+1isnumbered
-1;thereisnobase0
non-codingregions;
thenucleotide5'ofthe
ATG-translationinitiationcodonis-1
thenucleotide3'of
thetranslationterminationcodonis*1
intronic
nucleotides;
beginningofthe
intron:
thenumberofthelast
nucleotideofthepreceedingexon,aplussignandthepositioninthe
intron,e.g.77+1G,
77+2T(whentheexonnumberisknown,thenotationcanalsobedescribed
asIVS1+1G,
IVS1+2T)
endoftheintron:
thenumberofthefirstnucleotideofthe
followingexon,aminussignandthepositionupstreamintheintron,
e.g.78-2A,
78-1G(whentheexon
numberisknown,thenotationcanalsobedescribedasIVS1-2A,IVS1-2G)
fordeletions,duplications
orinsertionsinsinglenucleotide(oraminoacid)stretchesortandem
repeats,themost3'copyisarbitrarilyassignedtohavebeenchanged
(e.g.ACTTTGTGCCtoACTTTGCCisdescribedas7_8delTG)Descriptionofnucleotidechanges
substitutionsare
designatedbya“>”-character
76A>Cdenotesthatatnucleotide76aAischangedtoaC
88+1G>T(alternativelyIVS2+1G>T)denotestheGtoT
substitutionatnucleotide+1ofintron2,relativetothecDNApositioned
betweennucleotides88and89
89-2A>C(alternativelyIVS2-2A>C)denotestheAtoC
substitutionatnucleotide-2ofintron2,relativetothecDNA
positionedbetweennucleotides88and89
NOTE:
polymorphic
variantsaresometimesdescribedas76A/G,butthisisnotrecommened!
deletionsaredesignatedby"del"
afterthenucleotide(s)flankingthedeletionsite
76_78del
(alternatively76_78delACT)denotesaACTdeletionfromnucleotides76to
78
82_83del
(alternatively82_83delTG)denotesaTGdeletioninthesequenceACTTTGTGCC
(Aisnucleotide76)toACTTTGCC
IVS2_IVS5del
(alternatives88+?
_923+?
orEX3_5del)denotesanexonicdeletionstarting
atanunknownpositioninintron2(afternucleotide88)andendingatan
unknownpositioninintron5(afternucleotide923)
insertionsare
designatedby"ins"afterthe
nucleotidesflankingtheinsertionsite,followedbythenucleotides
inserted
NOTE:
asseparatorthe"^"-characterissometimesused
butthisisnotrecommened(e.g.83^84insTG)
76_77insT
denotesthataTwasinsertedbetweennucleotides76and77
83_84insTG
denotesaTGinsertionintheTG-tandemrepeatsequenceofACTTTGTGCC(A
isnucleotide76)toACTTTGTGTGCC.Notethatthissequence
variation(aduplicatinginsertion)canalsobedescribedasa
duplication,i.e.82_83dupTG(see"duplications")
variability
ofshortsequencerepeats,e.g.
inACTGTGTGCC(Aisnt1991),aredesignatedas1993(TG)3-6with
nucleotide1993containingthefirstTG-dinucleotidewhichisfound
repeated3to6timesinthepopulation.
insertion/deletions
(indels)aredescibed
asadeletionfollowedbyaninsertionafterthenucleotidesafected
112_117delinsTG
(alternatively112_117delAGGTCAinsTGor112_117>TG)denotesthe
replacementofnucleotides112to117(AGGTCA)byTG
duplicationsaredesignatedby"dup"afterthenucleotidesflankingthe
duplicationsite,
77_79dupCTG
denotesthatthenucleotides77to79wereduplicated
duplicating
insertionsinshorttandemrepeats(orsinglenucleotidestretches)can
alsobedescribedasaduplication,e.g.aTGinsertionintheTG-tandem
repeatsequenceofACTTTGTGCC(Aisnt76)toACTTTGTGTGCC
canbedescribedas82_83dupTG(now83_84insTG)
inversionsaredesignatedby"inv"afterthenucleotidesflankingthe
inversionsite
203_506inv
(or203_506inv304)denotesthatthe304nucleotidesfromposition203to
506havebeeninverted
translocations(nosuggestionsyet)
changesin
differentalleles(e.g.
inrecessivediseases)aredescribedas"[changeallele1]+[change
allele2]"
[76A>C]+[76A>C]denotesahomozygousAto
Cchangeatnucleotide76
[76A>C]+[?
]denotesaAtoC
changeatnucleotide76
inonealleleandanunknownchangeintheotherallele
two
variationsinoneallelearedescribedas"[firstchange
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