Designating genotypes: What does '+' really mean?

Learn how JAX designates mouse genotypes, and what “+” means in the ... “floxed, “flox,” or “fl” for the former, and an abbreviation for ... 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Geneticsvs.genomics Ethicalconsiderations Personalizedmedicineandyou WhatisCRISPR? MiceinBiomedicalResearch AreasofResearch Addiction Aging Alzheimer's&OtherDementias Cancer Diabetes Microbiome Rarediseases Vision ClinicalKnowledgebase MaineCancerGenomicsInitiative News  JAXNews JAXBlog MinutetoUnderstanding Subscribe PressRoom TheSearchMagazine ExplorebyTopic AboutUs  FastFacts OurPeople&Culture OurValues Diversity,Equity&Inclusion FacesofJAX OurLeaders WorkWithUs OurCampuses&Communities OurImpact CollaborationatJAX OurMedicalImpact OurEconomicImpact OurCommunityImpact OurEnvironmentalImpact OurHistory Careers ContactUs Give JAXHome NewsandInsights JAXBlog Designatinggenotypes:Whatdoes'+'reallymean? ByJimYeadon,Ph.D. BlogPostMay6,2011 InmanyofourJAXpresentationsandwebinars,wediscussrulesandnuancesofstrainandgenenomenclatureextensively,butverylittlementionismadeofhowgenotypesofindividualanimalsshouldbedesignated/symbolized.Inthispost,Iwouldliketocorrectthisoversight. AsfarasIknow,therearenocommittee-sanctionedrulesthatapplytodesignatingmousegenotypes.ThosethatIdescribebelow,therefore,arejustthosethatIandmycolleaguesintheJAXTechnicalInformationServices(TIS)grouptypicallyusewhendiscussingourmice.(WARNING!Idon’tpromiseyouthatourgenotypedesignationswillmakeperfectsense,onlythatIwillexplainthem!) First,wealwaysusethe“+”symboltoindicateawildtypeorunmodifiedallele,regardlessofthekindofstrainthatisbeingdescribed.Forspontaneouslyortargetedmutantmice,thisnotationmakesperfectsense:“+”indicatesthewildtypeallele,and“-”themutantallele.Thus,wedesignateourmousegenotypes“-/-”forhomozygousmutants,“+/-”forheterozygotes,and“+/+”forwildtypes.Prettystraightforward,sofar,Ithink. ForloxP-containingconditionaland“knockin”targetedmutations,themutantalleleisoftendesignatedusing,“floxed,“flox,”or“fl”fortheformer,andanabbreviationforwhateversequenceisknocked-intothelocus(e.g.cre,lacZ,EGFP,etc.)forthelatter;hencethegenotypesforhomozygotesandheterozygotesbecome,forexample,“fl/fl”and“fl/+”or“cre/cre”and“cre/+”,respectively. Withtransgenicmice,weuseaslightlydifferentconvention.Manyinvestigatorsuse“+”todesignateatransgenicallele.Thisconventionmakesgoodsensewhendiscussing“+/-”hemizygotes,buthomozygoustransgenicmicethenbecome“+/+,”whichcreatesconfusionforthoseofuswhotypicallyuse“+/+”toindicateawildtypemouse.Thisconventionalsoforceswildtypemicetobedesignated“-/-,”which,ofcourse,iscounter-intuitivetofolkswhouse“-”todesignateamutantallele. Toavoidsuchconfusion,theJAXTechnicalInformationServicesgrouptypicallyuses“Tg”todesignatetransgenicalleles.Thisallowustouse“Tg/Tg”toindicatehomozygoustransgenicmiceandtostilluse“+/+”todesignatethenon-transgenic,wildtypemouse.Itfollows,then,thatwemustuse“Tg/+”todesignatehemizygoustransgenicmice,right?Well,actually,no.BecausetransgenesareextrabitsofDNAinthemousegenomethathavenocorresponding“wildtype”sequenceintheunmodifiedgenome,wewritethegenotypesofhemizygousmiceas“Tg/0.″Thisconvention,wethink,helpstoavoidthetendencytointerpret“+/+”asmicethatarehomozygousforthetransgene.Why,then,don’tweuse“0/0″toindicatethewildtypeallele?Well,likeIsaid,wealwaysuse“+/+”todesignatea“wildtype”mouse,andwethinkthatthe“0/0″designationistoounconventionalformanymouseresearchers,especiallyforbeginners. AsIstatedearlier,therearenohardandfastrulesfordesignatingmousegenotypes,andyouarefreetochoosewhateverconventionsthatyoulike.Whichevertermsyouusetodesignateyourgenotypes,Iencourageyoutoprovidesomekeyorframeofreferencesothatinvestigatorswhoreadyourpapersandco-workerswhohavetoreadyouranimals’cagecardscaneasilyidentifywhichgenotypesarewhich.Ifanyofyouuseotherconventions,I’dlovetohearaboutthem! MoreLikeThis Theprogressofgeneticsequencing Wetakealookatthehistoryofgenomicsequencing,whereit'sgoinginthefuture,andthepowerithastopotentiallytreatdiseaseslikecancer. 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