the reliability of dna tests for inherited diseases

13-7-2015

The reliability of DNA tests for inherited diseases WhichoftheinternationallyofferedDNAtestsforinheriteddiseasesareusefulforcreatinghealthydogbreedsintheNetherlands.

MaaikeFennema(3574717)Prof.Dr.JanRothuizenDr.PeterLeegwater

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Abstract

Thechangeofthe‘’WetDieren’’,bytheDutchgovernment,requiresthebreederstoscreentheirparentaldogsforinheriteddiseases.SincethebreedersandtheveterinarianshavetoapplytheDNAtestsandtheydonothavealltheknowledgeaboutthesetest,thisstudyaimstomakealistincludingalltheavailableDNAtestontheDutchmarket.Toknowiftheofferedtestaresubstantiated,theywillbeevaluatedusingasetofcriteriadevelopedduringthisproject.First,alltheDNAtestweregatheredfromthefourbiggestlaboratoriesfortheDutchmarket,Laboklin,VetGen,VanHaeringenandOptigen.Thisresultedinalistcontaining120differentdiseases.Inthisarticlethefocuswasoncardiovascularandblooddiseases,metabolicandimmuneproblemsandeyedisorders.IftheDNAtestfulfilthecriteriatheywillbepublishedonthewebsiteof‘ExpertisecentrumGeneticaGezelschapsdieren’.Themostimportantcriterionwasthattherewasapeerreviewedarticleavailableaboutthemutationtheytestedon.SoforalltheDNAtests,articlesweresearchedandreviewed.Theresearchresultedinalistofintotal11cardiovascularandblooddiseases,23metabolicandimmuneproblemsand27eyedisorders.

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Introduction

InheriteddiseasesarethemostcommonhealthandwelfareproblemsinpurebredanimalsinTheNetherlands.Thewelfareofanimalshasbecomemoreimportantthelastyearssinceithasbecomeasubjectonthepoliticalagenda,asaresultthe‘WetDieren’(Lid2.62c.)hasbeenchanged.Sincethe1stofJuly2014breedersarerequiredtodoeverythingpossibletoproducehealthyoffspring.Duetothischange,breedersaresupposedtoscreentheparentaldogstheyuseforbreedingforinheriteddiseases.InheriteddiseasesarecausedbyamutationormutationsintheDNAofthedog.DNAtestscanshowifthesemutationsarepresentinindividualanimals.Ifthebreedersknowiftheparentaldogshaveamutationforaparticulardiseaseitispossibletoselectacombinationofparentalanimalswhichwillproduceoffspringthatisclinicallyhealthyfortheexamineddisease.

TherearemanyDNAtestsontheDutchmarket,someofthesetestsaretrustworthybutquiteafewarenotsubstantiatedorevencompletelyunsuited.Fortheveterinarianandforthebreeder,whohastoapplythetestandhastoconverttheoutcomeoftheDNAtestintoaproperbreedingpolicy,itisdifficulttoknowwhichteststheycanuseforareliableoutcome.Byreviewingalltheavailabletestsinascientificallysoundmanneritispossibletomakealistofreliabletests,whichcanbeusedbyveterinariansandbreeders.The‘ExpertisecentrumGeneticaGezelschapsdieren’ofthefacultyveterinarymedicinewillpublishthislistontheirwebsitesothattheveterinarianandbreedercanco-operatetobreedpurebredanimalsashealthyaspossible.AnotherimportantapplicationofDNAdiagnosticsforveterinarians,isthattheycandiagnosethegeneticsusceptibilityofindividualsinapopulationatyoungage,oftenbeforetheonsetofclinicaldisease.Thispermitstheveterinariantodesignanindividualhealthprogramtopreventordecreasetheclinicalstageofthedisease.

ToevaluateiftheDNAtestsareuseful,alistofcriteriahasbeendeveloped.TosetupqualitycriteriaforDNAtestsitisnecessarytounderstandwhichtypesofmoleculargeneticresearchexistandhowtheywork.TherearetwomaintypesofDNAtests.Thefirstisbasedonaknownmutationwhichcausesthedisease,whichisthebestandmostusedmethodtodiagnosethemutationcausingtheinheriteddisease.Thesecondtypeoftestisamarkertestwhichonlymarksthepartofthechromosomewheretheunknowncausalgenelies.Thismethodcanbeusediftheprecisemutationisnotyetknown.Itisalesscertainmethodbecausethegenewhichisbeingtestedoncannolongerbelinkedtothemutationbyrecombinationofthegenes.Thereforethemutationstestispreferredoverthemarkertest.Thereareotherfactorswhichplayaroleinsettingupthecriteria.Thepublishedpeerreviewedliteratureisanimportedone.ThearticlesaboutthemutationsconfirmthatreliableresearchhasbeendoneandthattheDNAtestisbasedonvalidevidence.Itisalsonecessarytoknowforwhichbreedthetestisusefulandhowamutationisinherited.

InthisreportalltheDNAtestsofferedbythefourbiggestlaboratoriesfortheNetherlands,Laboklin,VetGen,VanHaeringenandOptigen,willbescientificallyreviewedtodeterminethevalidityofthesetests.

Thisresearchprojectaims(1)todevelopcriteriatoreviewthequalityandapplicabilityofDNAtestsavailable,and(2)toapplythesecriteriafortheevaluationoftheDNAtestfordogsontheDutchmarket.Inthisprojectthefocuswasoncardiovascularandblooddiseases,metabolicandimmuneproblemsandeyedisorders.

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Material and methods

TheprojectsetsupalistofcriteriaforDNAtestsontheDutchmarket.Averyimportantcriterionwhichmustcomplywitheachtestisthebasisofapeerreviewedpublishedarticle.Whenanarticleaboutamutationispublisheditmaybeassumedthatfundamentalresearchisdoneandthatmethodsandresultshavebeenacceptedbypeersintheresearchfield.TestsbasedonsuchpublishedresultsareconsideredreliableDNAtests.Thearticlesshoulddescribeinwhichbreedthemutationoccursandinwhichcountrythemutationisfound.Itisalsousefultoknowhowthediseaseisinheritedandifthesamediseaseisduetoonemutationintodifferentmutationsinthesamegeneoreventwomutationsindifferentgenesindifferentbreeds.BecausethelistproducedinthisprojectisonlyaboutDNAtestsusefulintheNetherlandsonlythebreedsthatarebredintheNetherlandswereincluded.The‘’RaadvanBeheer’’hasalistofaldogbreedswhoarebredintheNetherlands.SothisisalsoacriterionDNAtestsinthedefinitivelistmustfulfil.

WiththeknowledgeofthecriteriatheavailableliteratureinthePennGendatabasewasused.Inthisdatabaseallthebreedsarelistedwiththeinheriteddiseasestheycanhaveandthemutationwhichcancausethediseaseswithareferencetothepublishedmanuscript.AlsoPubMedwassearchedtofindotherarticlesabouttheofferedDNAtestsandwerereviewedtojudgetheutilityandqualityoftheDNAtests.

TocreatethedefinitivelistofvalidDNAtestallthetestsavailablefromthefourbiggestlaboratories,activeontheNetherlandsmarket,weregathered.ThefourlaboratorieswhichwereexaminedareLaboklin,VetGen,VanHaeringenandOptigen.AllDNAtestswereorderedbybreed.Thisresultedagoodoverviewofwhichtestsareavailable.Thelengthofthelistrequiredadivisionintodifferentorgansystems.Thisprojectfocusedoncardiovascularandblooddiseases,metabolicandimmuneproblemsandeyedisorders.

ToknowifalllaboratoriesbasedtheirDNAtestsonreliablearticlesamailwassenttoaskonwhicharticlestheDNAtestsarebased.Thesemailsenclosedintheappendix.(Appendix5)TheyallusedthedatabaseofPennGen.AfterreviewingallthesearticlesabouttheDNAtestsalistwithalotofinformationabouttheDNAtestwasformed.ForallofferedDNAtestitwasassessedwhetherthemutationwasknownandhowtheresearchwasdone.OnthebasisofthisinformationalltheunsubstantiatedDNAtestshavebeenremovedfromthelistsoonlythereliabletestsarestillonthelist.

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Results

ByweighingthefactorsthatareusefultodetermineiftheDNAtestarevalid,thecriteriaweresetup.FirstwehavetoknowifthereisliteratureavailableforthemutationswheretheDNAtestarebasedon.Itisalsousefultoknowifatestisamarkeroramutationtest.Mutationtestsarebetterbecausetheyindicatethemutationitselfsoitisa100%surethetesteddoghasthemutation.Itisalsoimportanttoknownhowtheeffectofthemutationinherited.IsitrecessiveordominantandautosomalofX-linkedorotherwise?Toreviewalltheliterature,itwasnecessarytoknowwhichclinicalcriteriawereusedtoselectthecaseandcontrolgroupsinDNAresearchaswellasthestepstocometoavalidtest.Itisalsonecessarytoknowwhichbreedisusedtodeterminethemutationbecauseindifferentbreedsdifferentmutationsmayoccur.IfforexamplethemutationisfoundinaBeagleitisnotsureifaLabradorwiththesamediseasehadthesamemutation.Finally,decisionsregardingtheremaininglistshouldbemadebasedoncostoftheDNAtestandthetimeneededforthetestresult.

TheresultofgatheringalltheavailableDNAtestsfromLaboklin,VetGen,VanHaeringenandOptigenisalonglistwithmanyDNAtests.Atthispointthelistcontained120differentdiseasesand188differentbreeds.Notallthediseaseswereofferedforeachbreedbutthelistatthismomentcontains683combinationsofdiseasesandbreeds.(Seeappendix1)InthislistallavailableDNAtestsaresortedbybreed,soitisvisibleperbreedwhichinheriteddiseasecanbetested.Inthislistthereismoreinformationabouteachtest.Mostlythisisinformationthatisfoundonthedifferentsitesofthelaboratories.ThislistcontainsalltheDNAtestsavailableanddoesnotsayanythingaboutthevalidityoftheDNAtests.

Asdescribedabovethelistisdividedintodifferentorgansystemsbecauseofthelengthofthelist.Thisarticleisaboutblooddiseases,metabolicandimmuneproblemsandeyedisorders.Theresultofthiswasthreedifferentlistsforthethreedifferentgroupsofdiseases.(Seeappendix2)

InordertoobtainmoreinformationabouttheDNAtestsandtoknowifalltheavailableDNAtestsarereliable,theliteraturewasreviewed.TheresponsetothemailswehadsenttothelaboratorieswasthattheyallusedthedatabaseofPennGenfortherelevantpublications.(Appendix5).ThereweremanyarticlesinthePennGendatabasewhichhavebeenused.OtherinformationwasobtainedreviewingtheliteratureinPubMed.TheresultofthisresearchisanewlistwithalotmoreinformationabouttheDNAtests.(SeeAppendix3)

Someofthetestwereverywelldescribedinthearticles,forinstanceCoppertoxicosisinBedlingtonTerriers.InthisarticlethemutationisverypreciselydescribedfortheBedlingtonTerriers.Themutationisadeletionintheexon2oftheCOMMD1geneandthismutationisthemaincauseforcoppertoxicosisintheBelingtonTerrier(Forman,2005).InthiscaseitwasverystraightforwardthatthiswasagoodDNAtest.Thiswasthecasewithmanydiseasesofthelist,forinstancedryeyecurlycoatsyndromebytheCavalierKingCharlesSpaniel:thisdiseaseiscausedbyadeletionofasinglebase-pairintheFAM83Hgene.(Forman,Oliver2012)andalsoPyruvatekinasedeficiencyinsixdifferentdogbreeds(Basenjis,Cairnterrier,Westhighlandwhiteterrier,Labradorretriever,PugandBeagle).Forallthesebreedsdifferentmutationswerefound.FortheLabradorretriever,WesthighlandwhiteterrierandtheCairnterriertheyfoundthesamemutation,aC>Tmutationthatresultedinanearlystopcodon.InthePugandtheBeagletheyfoundtwodifferentmissense

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mutationsthatresultedinlossofenzymefunction.(Gultekin,2012)FortheBasenjistheyalsofoundamutationinthegenesoalsoforthisbreedtheDNAtestisvalidated.(Whitney,1995)

AnexampleofanincorrecttestisAchromatopsiatype1ordayblindness.ThisisaDNAtestofferedfortheLabradorretriever,althoughthereisnopeerreviewedpublishedarticleaboutanygeneticmutation.ThereforethiswasconsideredanunsubstantiatedDNAtest.ThesameappliesforHaemophiliaA(FactorVIIIdeficiency).Thereisnoproofinanyarticlethatthemutationforthisdiseaseishasbeenfound.Thereforethistestcanbeconsideredunreliable,meaningitshouldnotbeoffered.

Forotherdiseasesthemutationwasknownforonebreedbutalsoofferedfordifferentbreeds,forexampleFactorVIIdeficiency.FactorVIIisnecessaryfortheinitiationofcoagulationoftheblood.Whenadogisdeficientforthisfactoritwillleadtoableedingdisorder.Thearticleaboutthemutationonlyconcernsthebeagle.(Callan,2006)NeverthelesstheDNAtestforthismutationisalsoofferedforthegiantschnauzer,theAiredaleterrier,theAlaskankleekaiandtheScottishdeerhound.Forthesedogbreedstherearenoscientificarticlesavailable,whichmeanstheDNAtestisnotsupportedinascientificallymanner.InothercaseswhenaDNAtestisoffered,thesupportingarticle,whichshouldsupportthetestbydescribingthemutation,actuallystatesthatthestudyofthemutationhasnotyetrevealedthegene.ThisisthecasefordilatedcardiomyopathyintheDobermanpincher.Thearticleisaboutalargestudywith141Dobermanpinchers.Eventhoughtheyinvestigatedmanygenes,theydidnotfindthespecificgeneforthisdisease.(Mausberg,Theresa-Bernadette2011)Therewereotherarticlesavailable(Meurs,Kathryn2012).Forinstance,onearticledescribedfindinga16-bpdeletioninthePDK4genethatisassociatedwithcardiomyopathyinDobermanpinschers.However,anotherarticlerespondstothatwitharesearchintheEuropeanpopulationwherenoevidencewasfoundforthePDK4geneinvolved.(Owczarek-Lipska,2013)Thisinconclusiveinformationindicatestheneedformoreresearch. ThisisalsothecaseforVon-WillebrandsDisease.Therearethreetypesofthisdiseaseofwhichtype1isthemostcommon.Type2islesscommonbutwhenadogisaffectedtheclinicalsymptomsaremoresevere.Moreover,type3istherarestform,whichisalsotheworstformadogcansufferfrom.TheDNAtestisofferedforalltheVon-WillebrandsDiseasetypesandforalotofbreeds,especiallyVon-WillebrandsDiseaseType1.ThisDNAtestisavailableforelevendifferentdogbreeds.Thearticleaboutthemutation(Rieger,1998)revealsthereisnoknowledgeaboutthegeneticbackgroundofVon-WillebrandsDiseaseType1.Fortheothertypesamutationwasdiscoveredonlyforasmallnumberofdogbreeds.Sothetestisavailableforalotofbreedsbutonlyfoundinacoupleofbreeds.Thisisthesameforprimarylensluxation.Thistestisofferedfor28differentbreedsmostlyterriers.InthearticleabouttheADAMST17genetheyexamined30differentdogbreeds.Only17ofthescreenedbreedshadthemutationintheADAMTS17gene.TheotherbreedsdosuffersfromprimarylensluxationbutthemutationthatcausesthediseaseisnottheADAMTS17geneoradifferentmutationisthesamegene.(Gould,2011)TheavailableDNAtestfortheelevenremainingbreedsarenotsupportedbyanyliterature.

AverydifficultinheriteddiseaseisProgressiveRetinalAtrophy.TherearealotoftypesofPRAandmanygenesplayaroleinthisdisease.OnestudywasperformedonthegenesofPRA.(Downs,Louise2014)Theyscreened231dogs,representing36dogbreeds,for17differentmutationswhichcausePRA.Theresultofthislargestudywasthat129dogswerehomozygous,29dogswerecarriersandtheremaining73dogshadnomutationonthe

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testedalleles.Fromallthe36testedbreedonlyin21breedsamutationswasfound.Anotherinterestingaspectisthatthediseasewasfoundtobeheterogeneousin15ofthese21breeds,soitiscausedbyatleasttwomutations.For102dogsthemutationsremainunknown.Thesenumbersindicatethecomplexityofthisdisease.Inappendix3allthedifferenttypesofPRAandthebreedsaredescribed.

Itwasalsoimportanttolookifthesamediseasehasdifferentmutationsindifferentbreeds.Thiswasthecaseforpyruvatekinasedeficiency.TheBasenjis,Cairnterrier,WesthighlandWhiteTerrierLabradorRetrieverhavethesamemutationbutthePugendtheBeaglehavetwodifferentmutationforthesamedisease.

SincethelistisonlyforDutchbreederandveterinariansonlythebreedsthatareregisteredbythe‘’RaadvanBeheer’’areincluded.Acoupleexamplesofthebreeds,forthosewhothetestsareofferedbutthebreedsarenotregistered,aretheAlaskankleekai,ItalianGreyhound,SmallMunsterlander,PolishLowlandSheepdog.Anothertypesofbreedsarethebreedsthatarecalleddifferentlyindifferentcountries.ForinstancetheAmericanshepherdandtheLlewellinSetter.TheAmericanshepherdistheAmericanname,whereasinEuropetheycallthisbreedtheAustralianshepherd.TheLlewellinSetteristhepurestrainformoftheEnglishsetter.(Sparks,Troy2002)Mostofthesebreeds,whichwerenotdescribedintheliterature,werealreadyremovedfromthelistsincetheydonothavethemutation.

Throughthisresearchthe683originalcombinationsofDNAteststhatareofferedwasreducedtoonlythegoodandsubstantiatedDNAtest.Inappendix4thedefinitivelistisincluded.Thelistcontainselevenofcardiovascularandblooddiseases,23metabolicandimmuneproblemsand27eyedisorders.

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Discussion/Conclusion AftersettingthecriteriafortheDNAtest,manycriteriaseemedveryimportant.Duringtheprojecttheuseallofthecriteriawasrevised,forexample‘inwhichcountryisthetestdesigned?’’.ThetestsaremostlydesignedinothercountriesthanTheNetherlands.Inthearticlesitisoftendescribedwherethedogscomefromandthereforethecountrywherethetestismostlikelymade.However,thisisdifficulttoestablishforalltheDNAtestssothiscriterionisconsideredlessimportant.ForthebestresultsallthetestshavetobetestedinTheNetherlands,whichisanalmostimpossibletask.ThereisalsothecriteriaofhowtheDNAtestsaredeveloped.Thiswashardtoexaminebecausetheliteraturewasoftenonlyaboutthemutation.Thelaboratoriesmakeallthetestthemselves.(Seethemailsinappendix5).Thecriteriaabouthowtheeffectsofthemutationsinheritisusefulbecausethedominantdiseasesareonlyusefultotestifthediseaseonlyoccursinoldageddogs.Otherwisethediseasecanbeseenbeforethedogsisusedforbreeding.TheDNAtestsareparticularlyusefulinordertodetectcarriersofrecessivediseases.ThecriteriaofwhatkindofDNAtestisconducted,markerofmutationtestwasaveryimportantcriteria.WhentheprojectprogresseditappearedthatalltheofferedDNAtestweremutationtest.Thetwocriteriathatarethemostimportantare:(1)ifthereisliteratureavailableand(2)forwhichbreedistheDNAtestcreated?ThesewerethetwocriteriatowhichalltheDNAtestmustcomply. Thereviewingtheliteratureindicatedsomeinterestingfindings.Whengatheringalltheinformationfromthelaboratoriessometimestwodifferentnamesforthesamediseasewasused.Mostlytheyhadthesamemutationsowecouldcombinethem.ForexampleVanHaeringencalledadiseaseMultidrugResistance1whileLaboklincalleditIvermectinhypersensitivity(MDR1genedefect).AlsothedatabaseofPenGenndidnotalwaysprovidetheproperinformation.SomearticlesdidnotexistanymoresootherarticlesweresoughtinPubMed.TherewereacoupleofdiseaseswhichwereofferforallbreedsforexampleThrombasthenia2.ThearticleisonlyaboutthePyreneanMountainDogsoalltheotherbreedsarenotsupported.Therewerealsodifficultieswithsomebreeds,forinstancethecollies.InAmericathecolliesarenotdividedindifferentbreedsbutinEuropetherearealotofdifferentcollies.Otherbreedsarenotregisteredbythe‘’RaadvanBeheer’’sowedidnotincludetheminthedefinitivelist.Sometimesthelaboratoriesclaimtheyfoundamutationbythemselvesforaparticularbreed.Inthiscasethereisnopublicationavailablesowecannotknowwhethertheseclaimsaresubstained.Von-Willebranddiseasetype1isanotsoseverediseasethatisverycommon.Everydog,withtheriskofthisdiseasecouldbetestedbutthatisalittleexaggerated.Itisalsoadvisableonlytestthedogswhoundergosurgeryforexample.

TheoverallconclusionofthisprojectisthatalotofresearchhasbeenonDNAtestsandmanyoftheofferedDNAtestswerevaluabletests.Howevertherearealotoftests,whicharenotbasedonanypeerreviewedarticlesorthearticleswereeasilymisinterpreted.Insomecasesitlookedliketherewasamutationfoundbutactuallythereismoreresearchnecessary.SincethelaboratoriesarestilldoingalotofinvestigationonDNAtests,thelistwillbelongerandmorecompleteoverthecourseofthenextfewyears.

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Goldstein,O.,Mezey,J.,Schweitzer,P.,Boyko,A.,Gao,C.,Bustamante,C.,etal.(2013).IQCB1andPDE6Bmutationscausesimilarearlyonsetretinaldegenerationsintwocloselyrelatedterrierdogbreeds.InvestigativeOphthalmology&VisualScience,54(10),7005-19.doi:10.1167/iovs.13-12915

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11

Gould,D.(2011).ADAMTS17mutationassociatedwithprimarylensluxationiswidespreadamongbreeds.VeterinaryOphthalmology,14(6),378-384.doi:10.1111/j.1463-5224.2011.00892.x

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12

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13

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Appendix 1 Table1Listwithallthediseases.

Breeds Disease Mono/poly, recessive/dominant Mutation Which lab. Results Time/Price

17

All Breeds Caninedegenerativemyelopathy(DM) Autosomaalrecessive SOD1-gene Laboklin 3-5days

SOD1-gene VanHaeringen <20days€79,50

Hiplaxity1/2 Multifactorialorigin VanHaeringen <10days€39,50

Hyperuricemia(HUU) Autosomalrecessive SLC2A9Gene VanHaeringen <10days€39,50

Laboklin 3-5days

Maliganthyperthermia(MH) Autosomaldominant VanHaeringen <10days€39,50

Laboklin 1-2weeks

MultidrugResistance1(MDR1) Autosomalrecessive MDR1Gene VanHaeringen <10days€80,00

Polycythemia Autosomaldominant JAK2Gene VanHaeringen <10days€39,50

Thrombasthenia2 Autosomalrecessive VanHaeringen <10days€39,50

Airedale Terrier FaktorVII-Deficiency Autosomalrecessive Laboklin 3-5days

VetGen $65.00USD

HemophiliaB(FacortIXdeficiency) X-linkedrecessive VetGen $65.00USD

Alaskan Klee Kai FaktorVII-Deficiency Autosomalrecessive Laboklin 3-5days

VetGen $65.00USD

Alaskan malamute Polyneuropathy1 Autosomalrecessive Laboklin 1-2weeks

VanHaeringen <10days€39,50

ConeDegeneration(CD) Autosomalrecessive CNGB3Gene Optigen

American Bulldog Neuronalceroidlipofuscinosis(NCL)10 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

CSTDGene VetGen $65.00USD

CanineMulti-focalRetinopathy(CMR) Autosomalrecessive VMD2Gene Optigen US$95.00


American Cocker Spaniel Phosphofructokinasedeficiency(PFKD) Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD

prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00

FN(FamilialNephropathy) Autosomalrecessive VanHaeringen <10days€110,00

18

American Eskimo Dog prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00

prcdGene Optigen $195

Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days

2-20%ofcarrierswilldevelopcondition Optigen $90

Thrombopathia2 Autosomalrecessive VanHaeringen <10days€39,50

American Hairless Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days


American Pitbull Terrier CerebellarAtaxia/Neuronalceroidlipofuscinosis(NCL),4A Autosomalrecessive Optigen 3-4weeks$150

ConeRodDystrophy2(CRD2) Autosomalrecessive Optigen <2weeks$120

American Staffordshire Terrier CerebellarAtaxia/Neuronalceroidlipofuscinosis(NCL),4A Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Optigen 3-4weeks$150

ConeRodDystrophy2(CRD2) Autosomalrecessive VanHaeringen <25days€100,00

Hyperuricosuria(HU) Autosomalrecessive VetGen $65.00USD

Australian Cattle Dog Cystinuria Autosomaldominant Laboklin 1-2weeks VanHaeringen <10days€39,50

MyotoniaCongenita2 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks



rcd4ProgressiveRetinalAtrophy(rcd4PRA) Autosomalrecessive Laboklin 1-2weeks

C2orf71Gene Optigen $95


(sequel )Australian Cattle Dog



Carriershaveasmallchanceofgettingsick. VetGen $65.00USD

19


Australian Shepherd CMR1(CanineMultifocalRetinopathy) Autosomalrecessive VanHaeringen <10days€39,50

BEST1gene VetGen $65.00USD

VMD2Gene Optigen US$95.00

CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks

chromosomenumber37

Optigen $180

CyclicNeutropenia(CN) Autosomalrecessive VetGen $65.00USD

HereditaryCataract(HC) Autosomaldominant HSF4Gene VanHaeringen <10days€39,50

Laboklin 1-2weeks

Autosomalco-dominant HSF4-2Gene Optigen $100

Hyperuricosuria(HU) Autosomalrecessive VetGen $65.00USD

Ivermectinhypersensitivity(MDR1genedefect) Autosomalrecessive mdr1gene Laboklin 1-2weeks



ConeDegeneration(CD) Autosomalrecessive CNGB3Gene Optigen $160

Australian Silky Terrier prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00

Australian Stumpy Tail Cattle Dog

prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive prcdGene Optigen $195

Basenjis Pyruvatekinasedeficiency(PK) Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD

Optigen $80

BasenjiProgressiveRetinalAtrophy(basPRA) Autosomalrecessive Optigen $95


Basset Thrombopathia Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

X-linkedseverecombinedImmunodeficiency(X-SCID) X-Chromosomal VanHaeringen <10days€39,50

Laboklin 1-2weeks

20

Beagle FactorVIIdeficiency Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 3-5days

VetGen $65.00USD

Primaryopenangleglaucoma(POAG) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

ADAMTS10 Optigen $95

Musladin-Luekesyndrome(MLS) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 3-5days

CobalaminMalabsorption/cubilindeficiency Autosomalrecessive Laboklin 3-5weeks

Neonatalcorticalcerebellarabiotrophy(NCCD) Autosomalrecessive Laboklin 1-2weeks


OsteogenesisImperfecta Autosomaldominant VanHaeringen <10days€39,50

PyruvatekinaseDeficiency3(PKDef) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD

Bearded Collie CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks


chromosomenumber37

Optigen $180

Bedlington Terriers Coppertoxicosis Autosomalrecessive Laboklin 1-2weeks


Commd1 VetGen $65.00USD


Bernese Mountain Dog Von-WillebrandsDiseaseType1 Autosomaldominantvariablepenetrance VanHaeringen <10days€89,00

Laboklin 3-5days

VetGen Binnen2weeks$65.00USD

Bichon Frise Macrothrombocytopenia(MTC) Autosomaldominant beta-1tubulingene

VetGen $65.00USD

21

Black Russian Terrier hyperuricosuria(HU) Autosomalrecessive VetGen $65.00USD

Boerboel CMR1(CanineMultifocalRetinopathy) Autosomalrecessive VanHaeringen <10days€39,50


hyperuricosuria(HU) Autosomalrecessive VetGen $65.00USD

Bolonka Zwetna prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive prcdGene Optigen $195

Border Collie CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks


chromosomenumber37

Optigen $180

Ivermectinhypersensitivity(MDR1genedefect) Autosomalrecessive Mdr1gene Laboklin 1-2weeks

Neuronalceroidlipofuscinosis(NCL)5 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Optigen $95

TrappedNeutrophilSyndrome(TNS) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Optigen $95

CobalaminMalabsorption/cubilindeficiency Autosomalrecessive cubilingene Optigen $95

Boston Terrier HereditaryCataract2(HSF4) Autosomalrecessive HSF4Gene VanHaeringen <10days€39,50

Laboklin 1-2weeks

HSF4Gene VetGen $65.00USD

HSF4-1Gene Optigen $100

CobalaminMalabsorption/cubilindeficiency Autosomalrecessive Laboklin 3-5weeks

Boxer Macrothrombocytopenia(MTC) autosomaldominant beta-1tubulingene

VetGen $65.00USD


Boykin Spaniel CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks

chromosomenumber37

Optigen $180

Exerciseinducedcollapse(EIC) Autosomalrecessive DNM1gene Laboklin 3-5days

22

Brazilian Terrier MucopolysaccharidoseTypeVII-2 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Briard Congenitalstationarynightblindness(CSNB) Autosomalrecessive RPE65gene Laboklin 1-2weeks


RPE65Gene Optigen $135

Braittany Spaniel C3Deficiency Autosomalrecessive VanHaeringen <10days€39,50

Bull Dog CanineMultifocalRetinopathy(CMR1&CMR2) Autosomalrecessive BEST1gene VetGen $65.00USD


Bull Mastiff CanineMultifocalRetinopathy(CMR1&CMR2) Autosomalrecessive BEST1gene VetGen $65.00USD


DominantProgressiveRetinalAtrophy(PRA) Autosomaldominant VanHaeringen <10days€39,50

Laboklin 1-2weeks

Optigen ong.2weeks$120

Bull Terrier Polycystickidneydisease(PKD1) Autosomaldominant VanHaeringen <10days€39,50

Laboklin 1-2weeks


Cairn Terrier GloboidCellLeukodystrophy/KrabbesDisease Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Pyruvatekinasedeficiency(PK) Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD


Cane Corsos CMR1(CanineMultifocalRetinopathy) Autosomalrecessive vanHaeringen <10days€39,50




Cardigen Welsh Corgi rcd3ProgressiveRetinalAtrophy(rcd3PRA) Autosomalrecessive vanHaeringen <10days€39,50

VetGen $65.00USD

23

PDE6AGene Optigen $80

Cavalier King Charles Spaniel Dryeyecurlycoatsyndrome(CCS) Autosomalrecessive Laboklin 3-5days


EpisodicFalling(EF) Autosomalrecessive Laboklin 3-5days


Musculardystrophy(MD) X-chromosomal-recessive Laboklin 1-2weeks

Thrombocytopaenia Autosomalrecessive VanHaeringen <10days€39,50

Macrothrombocytopenia(MTC) autosomaldominant beta-1tubulingene

VetGen $65.00USD

Chesapeake Bay Retriever Ectodermaldysplasia/Skinfragilitysyndrome(ED/SFS) Autosomalrecessive Laboklin 1-2weeks


DNM1gene VanHaeringen <20days€59,50



Chihuahua Macrothrombocytopenia(MTC) autosomaldominant beta-1tubulingene

VetGen $65.00USD

Chinese Crested Dog CanineMultipleSystemDegeneration(CMSD) Autosomalrecessive Laboklin 1-2weeks







Von-WillebrandsDiseaseType2 Autosomalrecessive VetGen $65.00USD

rcd3ProgressiveRetinalAtrophy(rcd3PRA) Autosomalrecessive PDE6AGene Optigen $80

Chinese Foo Dog Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days



24

Clumber Spaniel PyruvateDehydrogenasePhosphatase1(PDP1) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD

Cockapoo prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


Phosphofructokinasedeficiency(PFKD) Autosomalrecessive Optigen $80

English Cocker Spaniel FamilialNephropathy(FN) Autosomalrecessive VanHaeringen <10days€110,00


Phosphofructokinasedeficiency(PFKD) Autosomalrecessive VetGen $65.00USD

Optigen $80


VetGen $65.00USD

Collies GrayCollieSyndrome(CyclicNeutropenia) Autosomalrecessive VanHaeringen <10days€39,50

CollieEyeAnomaly(CEA) Autosomalrecessive VanHaeringen <25days€140,00

Laboklin 1-2weeks

VetGen $65.00USD

chromosomenumber37

Optigen $180


rcd2ProgressiveRetinalAtrophy(rcd2PRA) Autosomalrecessive VanHaeringen <25days€187,50

Laboklin 1-2weeks

Optigen $180



Coton de Tulear Bandara’sNeonatalAtaxia(BNAt) Autosomalrecessive GRM1gene VetGen $65.00USD


CMR2(CanineMultifocalRetinopathy) Autosomalrecessive vanHaeringen <10days€39,50


25


Von-WillebrandsDiseaseType1 Autosomaldominant(variablepenetrance) VanHaeringen <10days€89,00

Laboklin 3-5days


Curly Coated Retrievers Exerciseinducedcollapse(EIC) Autosomalrecessive DNM1gene Laboklin 3-5days


GlycogenStorageDiseaseGSDTypeIIIa(GSDIIIa) Autosomalrecessive AGLGene VanHaeringen <20days€44,50

Laboklin 1-2weeks

Cone-RodDystrophy1-PRA(Cord1-PRA) Autosomalrecessive VetGen $65.00USD

Czechoslovakian Wolfdog Pituitarydwarfism Autosomalrecessive VanHaeringen <20days€69,50

Laboklin 1-2weeks

Dachshund OsteogenesisImperfecta Autosomalrecessive Laboklin 1-2weeks


ConeRodDystrophy4-PRA(CRD4-PRA) Autosomalrecessive VanHaeringen <10days€39,50


Progressiveretinalatrophy(crd-PRA) Autosomalrecessive NPHP4gene Laboklin 1-2weeks

MucopolysaccharidosisTypeIIIa Autosomalrecessive VanHaeringen <10days€39,50

Narcolepsy Autosomalrecessive VanHaeringen <20days€49,50

Hcrtr2Gene Optigen $130

Neuronalceroidlipofuscinosis(NCL)1/2 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Dalmation hyperuricosuria(HU) Autosomalrecessive VetGen $65.00USD


Doberman Pincher Albinism(White) Autosomalrecessive OCA4gene VetGen $65.00USD

DilatedCardiomyopathy Autosomalrecessive VanHaeringen <10days€39,50

VetGen $65.00USD

26


Laboklin 1-2weeks




Laboklin 3-5days

Dogue de Bordeaux CanineMulti-focalRetinopathy(CMR) Autosomalrecessive VMD2Gene Optigen US$95.00

Drentsche Patrijshond Von-WillebrandsDiseaseType1 Autosomaldominant(variablepenetrance) VanHaeringen <10days€89,00


Laboklin 3-5days

Dutch Kooiker VonWillebranddisease3-2 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD

Dwarf Poodle prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


English Bulldog CanineMultifocalRetinopathy(CMR1&CMR2) Autosomalrecessive BEST1gene VetGen $65.00USD

English Cocker Spaniel FamilialNephropathy(FN) Autosomalrecessive VanHaeringen <10days€110,00

Laboklin 1-2weeks

Optigen $95





(sequel) English Cocker Spaniel Phosphofructokinasedeficiency(PFKD) Autosomalrecessive VetGen $65.00USD

Optigen $80


VetGen $65.00USD

English Mastiff DominantProgressiveRetinalAtrophy(PRA) Autosomaldominant Laboklin 1-2weeks

27

CanineMultifocalRetinopathy(CMR1&CMR2) Autosomalrecessive BEST1gene VetGen $65.00USD

English Setter Neuronalceroidlipofuscinosis(NCL)8 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

CSTDgene VetGen $65.00USD



English Shepherd prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive prcdGene Optigen $195

English Springer Spaniel Fucosidosis Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 102weeks

FamilialNephropathy(FN) Autosomalrecessive Laboklin 1-2weeks

Phosphofructokinasedeficiency(PFKD) Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD

Optigen $80


Tremor,X-linked X-Chromosomal VanHaeringen <10days€39,50

English Toy Spaniel Macrothrombocytopenia(MTC) autosomaldominant beta-1tubulingene

VetGen $65.00USD

Entlebucher Mountain Dog prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


Farm Collie rcd2ProgressiveRetinalAtrophy(rcd2PRA) Autosomalrecessive VanHaeringen <25days€187,50

Finnish Hound CerebellarAtaxia,progressiveearly-onset Autosomalrecessive VanHaeringen <10days€39,50

SEL1Lgene Laboklin 1-2weeks

GlycogenstoragediseasetypeII(PompeDisease) Autosomalrecessive Laboklin 1-2weeks


Finnish Lapphund prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


French Bulldog Hereditarycataract(HC) Autosomalrecessive HSF4gene Laboklin 1-2weeks


28


Frisian Water Dogs SCID2 Autosomalrecessive VanHaeringen <10days€39,50

Fox Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days

German Pinscher Von-WillebrandsDiseaseType1 Autosomaldominant(variablepenetrance) VanHaeringen <10days€89,00


Laboklin 3-5days

German Pointer Junctionalepidermolysisbullosa(JEB) Autosomalrecessive Laboklin 1-2weeks

Von-WillebrandsDiseaseType2 Autosomalrecessive VanHaeringen <10days€69,00

VetGen $65.00USD

Laboklin 3-5days


German Shepherd CanineLeukocyteAdhesionDeficiency(CLAD),Type3 Autosomalrecessive VanHaeringen <10days€39,50


MucopolysaccharidosisTypeVII Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks


Pituitarydwarfism Autosomalrecessive VanHaeringen <20days€69,50

Laboklin 1-2weeks

RenalCystadenocarcinomaandNodularDermatofibrosis Autosomaldominant VetGen $65.00USD


German Shorthaired Pointer ConeDegeneration Autosomalrecessive VanHaeringen <10days€39,50

CNGB3Gene Optigen $160


German Spaniel Phosphofructokinasedeficiency(PFKD) Autosomalrecessive Laboklin 1-2weeks

German Spitz prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive prcdGene Optigen $195

German WIrehaired Pointer HemophiliaB(FacortIXdeficiency) X-linkedrecessive VetGen $65.00USD


29

Giant Schnauzer FactorVII-Deficiency Autosomalrecessive Laboklin 3-5days

VetGen $65.00USD


Neuroaxonaldystrophy(NAD) Autosomalrecessive VanHaeringen <10days€39,50



Glen of Imaal Terrier ConeRodDystrophy3(CRD3) Autosomalrecessive VanHaeringen <25days€100,00

ADAM9Gene Optigen $120

Golden Retriever Epidermolysisbullosa,dystrophic(RDEB) Autosomalrecessive VanHaeringen <10days€39,50

GRPRA1(ProgressiveRetinalAtrophy) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Optigen $100

GRPRA2(ProgressiveRetinalAtrophy) Autosomalrecessive Optigen $100

Ichthyosis2 Autosomalrecessive VanHaeringen <10days€39,50

Optigen $120

MuscularDystrophy(GRMD) X-Chromosomal VanHaeringen <10days€39,50

Laboklin 1-2weeks



Gordon Setter CerebellarAtaxia2 Autosomalrecessive VanHaeringen <10days€39,50

rcd4ProgressiveRetinalAtrophy(rcd4PRA) Autosomalrecessive vanHaeringen <10days€39,50

Laboklin 1-2weeks



Great Dane CentronuclearMyopathy(cnm) Autosomalrecessive Laboklin 3-5days

Great Pyrenees CMR1(CanineMultifocalRetinopathy) Autosomalrecessive vanHaeringen <10days€39,50


30

Great Swiss Mountain Dog BleedingdisorderduetoP2RY12defect Mono,autosomaalrecessief P2RY12Gene VanHaeringen <10days€39,50

Greyhound Hereditarypolyneuropathy(HN) Autosomalrecessive Laboklin 1-2weeks


VetGen $65.00USD

NDRG1gene Optigen $95

Havanese HaemophiliaA(FactorVIII) X-Chromosomal VanHaeringen <20days€49,50

Laboklin 2-5days


VetGen $65.00USD

Hokkaido CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks


chromosomenumber37

Optigen $180

Husky GM1-Gangliosidosis Autosomalrecessive Laboklin 1-2weeks

Irish Setters CanineLeukocyteAdhesionDeficiency(CLAD),Type1 Autosomalrecessive Laboklin 3-5days


Optigen $135

Globoidcellleukodystrophy(Krabbedisease) Autosomalrecessive Laboklin 1-2weeks

Neuronalceroidlipofuscinosis(NCL)8 Autosomalrecessive VanHaeringen <10days€39,50


Laboklin 1-2weeks

Optigen $120

PDEBgene VetGen $65.00USD


Laboklin 1-2weeks



Irish Terrier DigitalHyperkeratosis(CornyFeet) Autosomalrecessive Laboklin 1-2weeks

31


Irish Wolfhound StartleDiseaseorHyperekplexia Autosomalrecessive Laboklin 1-2weeks

Italian Greyhound IGPRA1(ProgressiveRetinalAtrophy) AutosomalDominantwithIncompletePenetrance

Optigen $105

Jack Russell Terrier Lateonsetataxia(LOA) Autosomalrecessive (CAPN1)-gene Laboklin 1-2weeks

PrimaryLensLuxation(PLL) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 3-5days


SCID Autosomalrecessive VanHaeringen <10days€39,50


VetGen $65.00USD

Spinocerebellarataxia(SCA) Autosomalrecessive Laboklin 3-5days

Jagd Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days




Japanese chin/spitz

Karerlian Beardog prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


Kerry Blue Terrier CanineMultipleSystemDegeneration(CMSD) Autosomalrecessive Laboklin 1-2weeks



Laboklin 3-5days

Kelpie CerebellarAbiotrophy Autosomalrecessive VanHaeringen <10days€39,50

Kromfohrländer DigitalHyperkeratosis(CornyFeet) Autosomalrecessive Laboklin 1-2weeks


Kuvasz prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00



32

Labrador Retriever CentronuclearMyopathy(CNMorHMLR) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 3-5days

Cystinuria Autosomalrecessive Laboklin 1-2weeks




HereditaryNasalParakeratosis(HNPK) Autosomalrecessive VanHaeringen <20days€91,50

Laboklin 3-5days

SUV39H2gene Optigen $120


VetGen $65.00USD

Myotubularmyopathy(MTM) X-Chromosomal VanHaeringen <10days€39,50


Laboklin 1-2weeks




PyruvatekinaseDeficiency(PKDef) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD

RetinalDysplasiaRetinalFolds+OculoSkeletalDysplasia(RD+OSD)1 Autosomaldominant(incompletepenetrance) VanHaeringen <10days€39,50

Laboklin 4-6weeks

Optigen $160

SkeletalDysplasia2(SD2) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

AchromatopsiaType1/DayBlindness Autosomalrecessive Optigen $100


Lagotto Romagnolo Juvenileepilepsy Autosomalrecessive VanHaeringen <10days€39,50

33

Laboklin 3-5werkdays

LGI2gene Optigen $95

Lakeland Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days


Lancashire Heeler CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks


chromosomenumber37

Optigen $180


Laboklin 3-5days



Landseer Cystinuria Autosomalrecessive Laboklin 3-5days


Thrombopathia3 Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Lapponian Herder GlycogenstoragediseasetypeII(PompeDisease) Autosomalrecessive Laboklin 1-2weeks



CMR(CanineMulti-focalRetinopathy) Autosomalrecessive VMD2Gene Optigen US$95.00

Large munsterlander hyperuricosuria(HU) Autosomalrecessive VetGen $65.00USD

Leonberger LeonbergerPolyneuropathy1(LPN1) Autosomalrecessive Laboklin 1-2weeks

Lhasa Apso HemophiliaB(FacortIXdeficiency) X-linkedrecessive VetGen $65.00USD

Llewellin Setter rcd4ProgressiveRetinalAtrophy(rcd4PRA) Autosomalrecessive C2orf71Gene Optigen $95

Longhaired Whippet Ivermectinhypersensitivity(MDR1genedefect) Autosomalrecessive mdr1gene Laboklin 1-2weeks

CollieEyeAnomaly(CEA) Autosomalrecessive chromosomenumber37

Optigen $180


34

Lucas Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days


Maltese GlycogenStorageDiseaseTypel(GSDI) Autosomalrecessive VanHaeringen <10days€39,50


VetGen $65.00USD

Maltipoo prcdProgressiceRetinalAtrophy(prcdPRA) Autosomalrecessive prcdGene Optigen $195

Manchester Terrier Von-WillebrandsDiseaseType1 Autosomaldominant(variablepenetrance) VanHaeringen <10days€89,00


Laboklin 3-5days

Markiesje prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


Mastiffs CMR1(CanineMultifocalRetinopathy) Autosomalrecessive VanHaeringen <10days€39,50


DominantProgressiveRetinalAtrophy(PRA) Autosomaldominant VanHaeringen <10days€39,50

Optigen ong.2weeks$120

Macrothrombocytopenia(MTC) Autosomaldominant beta-1tubulingene

VetGen $65.00USD

McNab Ivermectinhypersensitivity(MDR1genedefect) Autosomalrecessive mdr1gene Laboklin 1-2weeks

Miniature American Shepherd CMR1(CanineMultifocalRetinopathy) Autosomalrecessive VanHaeringen <10days€39,50






Optigen $180


Miniature Australian Shepherd CanineMulti-focalRetinopathy(CMR) Autosomalrecessive VMD2Gene Optigen US$95.00



35


Optigen $180

HereditaryCateract(HD) Autosomalco-dominant HSF4-2Gene Optigen $100

Miniature Bull Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days




Miniature Pinscher Cystinuria Autosomaldominant Laboklin 1-2weeks


Miniature Poodle prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00



VetGen $65.00USD

Miniature Schnauzer MyotoniaCongenita Autosomalrecessive VanHaeringen <20days€49,50

Laboklin 3-5days

TypeAProgressiveRetinalAtrophy(TypeAPRA) Autosomalrecessive VanHaeringen <25days€132,50

Optigen $160

PersistentMuellerianDuctSyndrome(PMDS) sex-limitedautosomalrecessivetrait MISRIIGene Optigen $95

Moyen Poodle prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00

Newfoundland Cystinuria Autosomalrecessive Laboklin 3-5days

GeneSLC3A1 VanHaeringen <10days€39,50

VetGen $65.00USD

Optigen $80

Norfolk Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days

Norwegian Elkhound prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00



Norwich Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days

36


Nova Scotia Duck Tolling Retriever

CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks


chromosomenumber37

Optigen $180



Old Danish Pointer CongenitalMyasthenicSyndrome Autosomalrecessive VanHaeringen <10days€39,50

Old English Sheepdog (Bobtail) CerebellarAtaxia2 Autosomalrecessive VanHaeringen <10days€39,50



PrimaryciliaryDyskinesia(PCD) Autosomalrecessive Laboklin 1-2weeks


CollieEyeAnomalie(CEA) Autosomalrecessive VanHaeringen <25days€140,00

Otterhound Thrombasthenia Autosomalrecessive VanHaeringen <10days€39,50

Papillion Pap-ProgressiveRetinalAtrophy1(Pap-PRA1) Autosomalrecessive VanHaeringen <25days€100,00

Laboklin 1-2weeks

Optigen $90




Laboklin 3-5days

Parson Russell Terrier Lateonsetataxia(LOA) Autosomalrecessive CAPN1-gene Laboklin 1-2weeks



(sequel) Parson Russell Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days


37




VetGen $65.00USD

Spinocerebellarataxia(SCA) Autosomalrecessive Laboklin 3-5days

Patterdale Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days




Pembroke Welsh Corgi Exerciseinducedcollapse(EIC) Autosomalrecessive DNM1gene Laboklin 3-5days



Laboklin 3-5days

Perro de Presa Canarios CMR1(CanineMultifocalRetinopathy) Autosomalrecessive VanHaeringen <10days€39,50


Phalene Pap-ProgressiveRetinalAtrophy1(Pap-PRA1) Autosomalrecessive VanHaeringen <25days€100,00

Laboklin 1-2weeks

Optigen $90

Pitbull Terrier ConeRodDystrophy2(CRD2) Autosomalrecessive VanHaeringen <25days€100,00


Polish Lowland Sheepdog rcd4ProgressiveRetinalAtrophy(rcd4PRA) Autosomalrecessive Laboklin 1-2weeks


Pomeranian VitaminD-deficiencyrickets,typeII Autosomalrecessive VanHaeringen <10days€39,50

Poodle NeonatalEncephalopathy Autosomalrecessive ATF2Gene VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD


(sequel) Poodle Macrothrombocytopenia(MTC) autosomaldominant beta-1tubulin VetGen $65.00USD

38

gene



Laboklin 3-5days


Portuguese Water Dog GM1-Gangliosidosis Autosomalrecessive Laboklin 1-2weeks

Optigen $120



Pug NecrotizingMeningoencephalitis(NME) Autosomalrecessive(withvariablepenetrance) Laboklin 1-2weeks


PyruvatekinaseDeficiency2(PKDef) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD

Rat Terrier CongenitalHypothyroidism(CHG)3 Autosomalrecessive VanHaeringen <10days€39,50





Rhodesian Ridgeback HaemophiliaB(factorIXdeficiency) X-chromosomal-recessive Laboklin 3-5days

VetGen $65.00USD

Rough Collie rcd2ProgressiveRetinalAtrophy(rcd2PRA) Autosomalrecessive VanHaeringen <25days€187,50

Optigen $180


Optigen $180

Saarloos Wolfdog Pituitarydwarfism Autosomalrecessive VanHaeringen <20days€69,50

Laboklin 1-2weeks


39

Samoyed FamilialNephropathy(FN) X-chromosomal-recessive Laboklin 1-2weeks

VetGen $65.00USD

RetinalDysplasiaRetinalFolds+OculoSkeletalDysplasia(RD+OSD)2 Autosomalrecessive VanHaeringen <25days€132,50

Autosomal-dominantwithincompletepenetrance

Laboklin 4-6weeks

Autosomaldominantwithincompletepenetrance

Optigen $160

XLinkedProgressiveRetinalAtrophy1(XLPRA1) X-Chromosomal VanHaeringen <10days€39,50

Optigen $150

Schapendoes gPRA(ProgressiveRetinalAtrophy) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Schipperke prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00


Scottish Deerhound FaktorVII-Deficiency Autosomalrecessive Laboklin 3-5days

VetGen $65.00USD

Scottish Terrier Von-WillebrandsDiseaseType3 Autosomalrecessive VanHaeringen <10days€49,50

VetGen $65.00USD

Laboklin 1-2weeks

Sealyham Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days




Shetland Sheepdog CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks


chromosomenumber37

Optigen $180


Von-WillebrandsDiseaseType3 Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD


40

Shiba Inu GM1Gangliosidosis Autosomalrecessive VanHaeringen <10days€39,50

Shih Tzu Prekallikreindeficiency Autosomalrecessive VanHaeringen <10days€39,50


VetGen $65.00USD

Siberian Husky XLinkedProgressiveRetinalAtrophy1(XLPRA1) X-Chromosomal VanHaeringen <10days€39,50

Optigen $150

Silken Windhound Ivermectinhypersensitivity(MDR1genedefect) Autosomalrecessive mdr1gene Laboklin 1-2weeks


Optigen $180

Silky Terrier prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive prcdGene Optigen $195

Sloughi rcd1aProgressiveRetinalAtrophy(rcd1aPRA) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

PDE6Bgene Optigen $80

Small Munsterlander rcd4ProgressiveRetinalAtrophy(rcd4PRA) Autosomalrecessive Laboklin 1-2weeks


Smooth Collies rcd2ProgressiveRetinalAtrophy(rcd2PRA) Autosomalrecessive VanHaeringen <25days€187,50

Optigen $180


Optigen $180

Soft-Coated Wheaten Terrier Proteinlosingnephropathy(PLN) Autosomalrecessive Laboklin 3-5days

Spaniel breeds Phosphofructokinasedeficiency(PFK) Autosomalrecessive VanHaeringen <10days€39,50

Spanish Water Dog CongenitalHypothyreosis(CHG) Autosomalrecessive Laboklin 1-2weeks




Stabijhoun Von-WillebrandsDiseaseType1 Autosomaldominant(variablepenetrance) VanHaeringen <10days€89,00


Laboklin 3-5days


41

Staffordshire Bull Terrier HereditaryCataract2(HSF4) Autosomalrecessive HSF4Gene VanHaeringen <10days€39,50


HSF4gene Laboklin 1-2weeks


L2-Hydroxyglutaricaciduria(L2-HGA) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 3-5days

Sussex Spaniel PyruvateDehydrogenasePhosphatase1(PDP1) Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

VetGen $65.00USD

Swedish Lapphund GlycogenstoragediseasetypeII(PompeDisease) Autosomalrecessive Laboklin 1-2weeks



Teddy Roosevelt Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days


Tenterfield Terrier CongenitalHypothyroidism(CHG)2 Autosomalrecessive VanHaeringen <10days€39,50





Tibetan Terrier Neuronalceroidlipofuscinosis(NCL) Autosomalrecessive Laboklin 1-2weeks


Laboklin 3-5days






42

Toy Fox Terrier CongenitalHypothyroidism(CHG)3 Autosomalrecessive VanHaeringen <10days€39,50





Toy Poodle Gangliosidosis,GM2,typeII Autosomalrecessive VanHaeringen <10days€39,50



Volpino Italiano Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days




Wäller Hereditarycataract(HC) Autosomaldominant HSF4gene Laboklin 1-2weeks

Weimaraner Hypomyelination(ShakingPuppySyndrome) Autosomalrecessive Laboklin 1-2weeks

Welsh Corgi MuscularDystrophy,Duchennetype(MDM) X-Chromosomal VanHaeringen <10days€39,50


X-linkedseverecombinedImmunodeficiency(X-SCID) X-Chromosomal VanHaeringen <10days€39,50

Laboklin 1-2weeks

Welsh Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days




Westhighland White Terrier GloboidCellLeukodystrophy/KrabbesDisease Autosomalrecessive VanHaeringen <10days€39,50

Laboklin 1-2weeks

Pyruvatekinasedeficiency(PK) Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD

Westphalia Terrier Primarylensluxation(PLL) Autosomalrecessive Laboklin 3-5days


43

Whippet CollieEyeAnomalie(CEA) Autosomalrecessive Laboklin 4-6weeks

Optigen $180

MuscularHypertrophy Autosomaldominant VanHaeringen <10days€39,50

Autosomalrecessive Laboklin 1-2weeks

Phosphofructokinasedeficiency(PFKD) Autosomalrecessive Laboklin 1-2weeks

VetGen $65.00USD

White Shepherd Ivermectinhypersensitivity(MDR1genedefect) Autosomalrecessive mdr1gene Laboklin 1-2weeks

Whire-haired Fox Terrier Primarylensluxation(PLL) Autosomalrecessive VanHaeringen <10days€39,50



Wire-haired Pointer Exerciseinducedcollapse(EIC) Autosomalrecessive DNM1gene Laboklin 3-5days

Wolfdog DilatedCardiomyopathy Autosomalrecessive VanHaeringen <10days€39,50

Yorkshire Terrier prcdProgressiveRetinalAtrophy(prcdPRA) Autosomalrecessive VanHaeringen <25days€150,00






L2-HydroxyglutaricAciduria Autosomalrecessive VetGen $65.00USD

Appendix 2 Table2Cardiovascularandblooddiseases

Diseases Breeds

Bleeding disorder due to P2RY12 defect GreatSwissMountainDog

Cyclic Neutropenia (CN) (Gray Collie Syndrome) AustralianShepherd Collies

Dilated Cardiomyopathy DobermanPincher,Wolfdog

Factor VII - Deficiency GiantSchnauzer Beagle AiredaleTerrier

AlaskanKleeKai ScottishDeerhound

Haemophilia A (Factor VIII) Havanese

Haemophilia B (Factor IX deficiency) RhodesianRidgeback LhasaApso GermanWirehairedPointer

AiredaleTerrier BullTerrier CairnTerrier

GermanPointer

Macrothrombocytopenia (MTC) Boxer LabradorRetriever BichonFrise

CavalierKingCharlesSpaniel ShihTzu Poodle

Chihuahua ParsonRussellTerrier MiniaturePoodle

EnglishCockerSpaniel Mastiffs Maltese

EnglishToySpaniel JackRussellTerrier Havanese

Polycythemia AllBreeds

Thrombasthenia Otterhound

Thrombasthenia 2 AllBreeds

Thrombocytopaenia CavalierKingCharlesSpaniel

Thrombopathia Basset Landseer AmericanEskimoDog

Von-Willebrands Disease Type 1 BerneseMountainDog Stabijhoun Poodle

CotondeTulear PembrokeWelshCorgi Papillion

DobermanPincher ManchesterTerrier KerryBlueTerrier

DrentschePatrijshond GermanPinscher

Von-Willebrands Disease Type 2 ChineseCrestedDog GermanWirehairedPointer GermanPointer

Collies

Von-Willebrands Disease Type 3 DutchKooiker ScottishTerrier ShetlandSheepdog

Table3MetabolicandImmuneproblems

Diseases Breeds

C3 Deficiency BrittanySpaniel

Canine Leukocyte Adhesion Deficiency (CLAD), Type 1 IrishSetters

Canine Leukocyte Adhesion Deficiency (CLAD), Type 3 GermanShepherd

Cobalamin Malabsorption/cubilin deficiency Beagle BorderCollie BostonTerrier

Congenital Hypothyreosis (CHG) SpanishWaterDog

Congenital Hypothyreosis (CHG) 2 TenterfieldTerrier RatTerrier

Congenital Hypothyreosis (CHG) 3 ToyFoxTerrier

Copper toxicosis BedlingtonTerriers

Fucosidosis EnglishSpringerSpaniel

Glycogen Storage Disease GSD Type IIIa (GSDIIIa) CurlyCoatedRetrievers

45

Glycogen Storage Disease Type l (GSD I) Maltese

Ivermectin hypersensitivity (MDR1 gene defect) AustralianShepherd WhiteShepherd SilkenWindhound

Bobtail ShetlandSheepdog McNab

BorderCollie LonghairedWhippet GermanShepherd

Collies AllBreeds

Mucopolysaccharidose Type VII - 2 BrazilianTerrier

Mucopolysaccharidosis Type IIIa Dachshund

Mucopolysaccharidosis Type VII GermanShepherd

Phosphofructokinase deficiency (PFKD) Spanielbreeds Whippet GermanSpaniel

AmericanCockerSpaniel EnglishSpringerSpaniel EnglishCockerSpaniel

Cockapoo

Prekallikrein deficiency ShihTzu

Pyruvate Dehydrogenase Phosphatase 1 (PDP1) ClumberSpaniel SussexSpaniel

Pyruvate kinase Deficiency (PKDef) Basenjis LabradorRetriever WesthighlandWhiteTerrier

CairnTerrier

Pyruvate kinase Deficiency 2 (PKDef) Pug

Pyruvate kinase Deficiency 3 (PKDef) Beagle

Severe combined Immunodeficiency (X-linked-SCID) Basset WelshCorgi

Severe combined Immunodeficiency (SCID) JackRussellTerrier

Severe combined Immunodeficiency 2(SCID2) FrisianWaterDogs

Vitamin D-deficiency rickets, type II Pomeranian

Glycogen storage disease type II (Pompe Disease) FinnishHound LapponianHerder SwedishLapphund

Table4Eyedisorders

Diseases Breeds

Achromatopsia Type 1/Day Blindness LabradorRetriever

Albinism (White) DobermanPincher

Canine Multi-focal Retinopathy (CMR 1) AustralianShepherd AmericanBulldog DoguedeBordeaux

Boerboel MiniatureAustralianShepherd LapponianHerder

CaneCorsos PerrodePresaCanarios MiniatureAmericanShepherd

GreatPyrenees Mastiffs

Canine Multi-focal Retinopathy (CMR 2) CotondeTulear

Canine Multi-focal Retinopathy (CMR1 & CMR2)

BullDog BullMastiff EnglishBulldog

EnglishMastiff

Collie Eye Anomalie (CEA) AustralianShepherd MiniatureAustralianShepherd MiniatureAmericanShepherd

BeardedCollie RoughCollie SilkenWindhound

BorderCollie LonghairedWhippet Whippet

BoykinSpaniel ShetlandSheepdog Collies

Hokkaido Sheepdogs NovaScotiaDuckTollingRetriever

LancashireHeeler SmoothCollies

Cone Degeneration (CD) GermanShorthairedPointer MiniatureAustralianShepherd MiniatureAmericanShepherd

46

Alaskanmalamute AustralianShepherd

Cone Rod Dystrophy 2 (CRD2) AmericanPitbullTerrier GlenofImaalTerrier PitbullTerrier

AmericanStaffordshireTerrier

Cone Rod Dystrophy 4-PRA (CRD4-PRA) Dachshund

Cone-Rod Dystrophy 1-PRA (Cord1-PRA) CurlyCoatedRetrievers Papillion EnglishSpringerSpaniel

Dachshund

Congenital stationary night blindness (CSNB) Briard

Dry eye curly coat syndrome (CCS) CavalierKingCharlesSpaniel

Hereditary Cataract (HC) AustralianShepherd Wäller MiniatureAustralianShepherd

FrenchBulldog

Hereditary Cataract 2 (HSF4) BostonTerrier StaffordshireBullTerrier

Primary lens luxation (PLL) AmericanEskimoDog Pug RatTerrier

AmericanHairlessTerrier SealyhamTerrier TeddyRooseveltTerrier

AustralianCattleDog TenterfieldTerrier TibetanTerrier

ChineseCrestedDog PatterdaleTerrier ParsonRussellTerrier

ChineseFooDog NorwichTerrier NorfolkTerrier

FoxTerrier MiniatureBullTerrier ToyFoxTerrier

JackRussellTerrier VolpinoItaliano WelshTerrier

JagdTerrier WestphaliaTerrier Whire-hairedFoxTerrier

LakelandTerrier YorkshireTerrier LucasTerrier

LancashireHeeler

Primary open angle glaucoma (POAG) Beagle

Progressive Retinal Atrophy (prcd PRA) Maltipoo NorwegianElkhound FinnishLapphund

AmericanCockerSpaniel NovaScotiaDuckTollingRetriever

GermanSpitz

AmericanEskimoDog Poodle GiantSchnauzer

AustralianCattleDog PortugueseWaterDog GoldenRetriever

AustralianShepherd Schipperke KarelianBeardog

AustralianSilkyTerrier SilkyTerrier Kuvasz

AustralianStumpyTailCattleDog

SpanishWaterDog LabradorRetriever

BolonkaZwetna SwedishLapphund LapponianHerder

ChesapeakeBayRetriever ToyPoodle Markiesje

ChineseCrestedDog YorkshireTerrier MiniatureAmericanShepherd

Cockapoo EntlebucherMountainDog MiniatureAustralianShepherd

DwarfPoodle EnglishShepherd MiniaturePoodle

EnglishCockerSpaniel MoyenPoodle

Progressive Retinal Atrophy -Dominant- (PRA) BullMastiff Mastiffs EnglishMastiff

Progressive Retinal Atrophy (Basenji PRA) Basenjis

Progressive Retinal Atrophy (crd-PRA) Dachshund

Progressive Retinal Atrophy (gPRA) Schapendoes

Progressive Retinal Atrophy (GR PRA1 and 2) GoldenRetriever

Progressive Retinal Atrophy (IG PRA1) ItalianGreyhound

Progressive Retinal Atrophy (rcd1 PRA) IrishSetters Sloughi

47

Progressive Retinal Atrophy (rcd2 PRA) Collies SmoothCollies RoughCollie

FarmCollie

Progressive Retinal Atrophy (rcd3 PRA) CardigenWelshCorgi ChineseCrestedDog WelshCorgi

Progressive Retinal Atrophy (rcd4 PRA) AustralianCattleDog TibetanTerrier SmallMunsterlander

EnglishSetter PolishLowlandSheepdog LlewellinSetter

GordonSetter IrishSetters

Progressive Retinal Atrophy (Type A PRA) MiniatureSchnauzer

Progressive Retinal Atrophy 1 (Pap-PRA1) Papillion Phalene

Progressive Retinal Atrophy 1 (X Linked PRA1) Samoyed SiberianHusky

Retinal Dysplasia Retinal Folds OculoSkeletal Dysplasia (RD+OSD) 1 and 2

LabradorRetriever Samoyed

48

Appendix 3

CardiovascularsystemandblooddisordersBleedingdisorderduetoP2RY12defect GreatSwissMountainDog Mutationdescribedinarticle. (Boudreaux,2011)CyclicNeutropenia(CN) AustralianShepherd Noarticlefoundaboutthemutation. Collies Mutationdescribedinarticle. (Benson,2003)DilatedCardiomyopathy DobermanPincher Thisarticleisaboutthattheydonotknowthemutationyet.Wolfhound Noarticlefoundaboutthemutation.

(Mausberg,Theresa-Bernadette2011)FactorVII-Deficiency GiantSchnauzer NoarticlefoundaboutthemutationBeagle Mutationdescribedinarticle (Callan,MB2006)AiredaleTerrier NoarticlefoundaboutthemutationAlaskanKleeKai Breedisnotregisteredbythe‘’RaadvanBeheer’’ScottishDeerhound ThemutationisonlydescribedfortheBeagleHaemophiliaA(FactorVIII) Havanese Noarticlefoundaboutthemutation HaemophiliaB(FactorIXdeficiency)RhodesianRidgeback Mutationdescribedinarticle. (Mischke,2011)AiredaleTerrier Mutationdescribedinarticle. (Mauser,1996)BullTerrier Mutationdescribedinarticle. (Mauser,1996)CairnTerrier Mutationdescribedinarticlebutnobreed.(Evans,1989)GermanPointer Noarticlefoundaboutthemutation GermanWirehairedPointer Mutationdescribedinarticle. (Brooks,Marjory2003)LhasaApso Mutationdescribedinarticle. (Mauser,1996)Macrothrombocytopenia(MTC) Boxer ArticleinGenPennisaboutanotherdiseasenootherarticlefound.CavalierKingCharlesSpaniel Mutationdescribedinarticle (Davis,2008)Chihuahua,EnglishCockerSpaniel,EnglishToySpaniel,Havanese,JackRussellTerrier,Maltese,Mastiffs,MiniaturePoodle,ParsonRussellTerrier,Poodle,ShihTzu,BichonFrise,LabradorRetriever ThemutationonlydescribedintheCavalierKingCharlesSpaniel.Polycythemia AllBreeds OnlytestedonacoupleofbreedsMaltese,poodle,YorkshireTerrierandWestHighlandWhiteTerrierMutationdescribedinarticle.

(Beurlet,Stephanie2011)Thrombasthenia Otterhound Mutationdescribedinarticle. (Boudreaux,2001)

49

Thrombasthenia2 AllBreeds Noarticlefoundaboutthemutationaboutallbreeds.PyreneeseBerghond Mutationdescribedinarticle. (Lipscomb,2000) Thrombocytopaenia CavalierKingCharlesSpaniel Noarticlefoundaboutthemutation.Thrombopathia Basset,AmericanEskimoDog,Landseer Mutationdescribedinarticle(Boudreaux,Mary2007)Von-WillebrandsDiseaseType1BerneseMountainDog,CotondeTulear,DobermanPincher,DrentschePatrijshond,GermanPinscher,KerryBlueTerrier,ManchesterTerrier,Papillion,PembrokeWelshCorgi,Poodle,Stabyhoun. Articledescribesnomutationisyetfound.(Rieger,M.1998)Von-WillebrandsDiseaseType2ChineseCrestedDog,Collies,GermanPointer Noarticlefoundaboutthemutation.Germanwirehairedpointer Mutationdescribedinarticle(Kramer,2004) Von-WillebrandsDiseaseType3DutchKooiker,ScottishTerrier,ShetlandSheepdog Mutationdescribedinarticle(Rieger,M.1998)

Metabolicandimmunediseases C3Deficiency BrittanySpaniel Mutationdescribedinarticle(Ameratunga,1998) CanineLeukocyteAdhesionDeficiency(CLAD),Type1 IrishSetters Mutationdescribedinarticle(Kijas,1999)CanineLeukocyteAdhesionDeficiency(CLAD),Type3Germanshepherd Mutationdescribedinarticle(Boudreaux,2010)CobalaminMalabsorption/cubilindeficiency Beagle Mutationdescribedinarticle(Fyfe,2014)BorderCollie Mutationdescribedinarticle(Fyfe,John2013)BostonTerrier Noarticlefoundaboutthemutation.CongenitalHypothyreosis(CHG)1,2and3SpanishWaterDog,RatTerrier,ToyFoxTerrier Noarticlefoundaboutthemutation.TenterfieldTerriër Mutationdescribedinarticle(Dodgson,2012)Coppertoxicosis BedlingtonTerriers Mutationdescribedinarticle(Forman,2005)Fucosidosis Englishspringerspaniel Mutationdescribedinarticle(Skelly,1999)GlycogenStorageDiseaseTypel(GSDI)Maltese Mutationdescribedinarticle (Kishnani,1997)GlycogenStorageDiseaseGSDTypeIIIa(GSDIIIa)CurlyCoatedRetrievers Mutationdescribedinarticle (Gregory,Brittany2007)

50

Ivermectinhypersensitivity(MDR1genedefect)AllBreed OnlytestedonacoupleofbreedsAustralianShepherd,Collies,BorderCollie,ShetlandSheepdog,WhiteShepherd,GermanShepherdLonghairedWhippet,SilkenWindhound Mutationdescribedinarticle (Mealey,Katrina2008)Bobtail Noarticlefoundaboutthemutation.McNab Breedisnotregisteredbythe‘’RaadvanBeheer’’. MucopolysaccharidoseTypeVII-2 BrazilianTerrier Mutationdescribedinarticle(Hytonen,2012) MucopolysaccharidosisTypeVII GermanShepherd Mutationdescribedinarticle(SilversteinDombrowski,Deborah2004)MucopolysaccharidosisTypeIIIaDachshund Mutationdescribedinarticle(Aronovich,EL2000)Phosphofructokinasedeficiency(PFKD) AmericanCockerSpaniel,GermanSpaniel,Whippetn Mutationdescribedinarticle(Giger,U1992)Cockapoo Noarticlefoundaboutthemutation. EnglishCockerSpaniel Noarticlefoundaboutthemutation. EnglishSpringerSpaniel Mutationdescribedinarticle (Smith,1996) PrekallikreindeficiencyShihTzu Mutationdescribedinarticle (Okawa,Takumi2011)PyruvateDehydrogenasePhosphatase1(PDP1) ClumberSpaniel,SussexSpaniel Mutationdescribedinarticle(Cameron,Jessie2007)PyruvatekinaseDeficiency(PKDef)Basenjis Mutationdescribedinarticle(Whitney,1995)CairnTerrier Mutationdescribedinarticle(Gultekin,2012)WesthighlandWhiteTerrier Mutationdescribedinarticle(Skelly,1999)LabradorRetriever Mutationdescribedinarticle(Gultekin,2012)Type2Pug Mutationdescribedinarticle(Gultekin,2012)Type3Beagle Mutationdescribedinarticle(Gultekin,2012)SeverecombinedImmunodeficiency(X-linked-SCID) Basset,WelshCorgi Mutationdescribedinarticle(Perryman,2004)SeverecombinedImmunodeficiency(SCID) JackRussellTerrier Mutationdescribedinarticle(Meek,2001)SeverecombinedImmunodeficiency2(SCID2) FrisianWaterDogs Mutationdescribedinarticle(Verfuurden,2011)TrappedNeutrophilSyndrome(TNS)BorderCollie Mutationdescribedinarticle(Mizukami,Keijiro2012)VitaminD-deficiencyrickets,typeII Pomeranian Mutationdescribedinarticle.(LeVine,2009)GlycogenstoragediseasetypeII(PompeDisease) FinnishHound NoarticlefoundaboutthemutationLapponianHerder,SwedishLapphund Mutationdescribedinarticle(Seppälä,Eija2013)

51

EyediseasesAchromatopsiaType1/DayBlindness LabradorRetriever NoarticlefoundaboutthemutationAlbinism(White) DobermanPincher Mutationdescribedinarticle (Winkler,Paige2014)

CanineMulti-focalRetinopathy(CMR)AustralianShepherd Mutationdescribedinarticle (Hoffmann,Ingo2012)Boerboel Mutationdescribedinarticle (Gornik2014) GreatPyrenees,Mastiffs, Mutationdescribedinarticle (Guziewicz,Karina2007)AmericanBulldog,CaneCorso,DoguedeBordeaux,MiniatureAustralianShepherd,LapponianHerder,BullDog,BullMastiff,EnglishBulldog,EnglishMastiff

NoarticlefoundaboutthemutationMiniatureAmericanShepherd,PerrodePresaCanariosBreedsarenotregisteredbythe‘’RaadvanBeheer’’CanineMulti-focalRetinopathy(CMR2)CotondeTulear Mutationdescribedinarticle(Guziewicz,Karina2007)CollieEyeAnomalie(CEA) AustralianShepherd,BeardedCollie,BorderCollie,BoykinSpaniel,LancashireHeeler,NovaScotiaDuckTollingRetriever,Sheepdogs,ShetlandSheepdog,Whippet,Collies,LonghairedWhippet,MiniatureAustralianShepherd,RoughCollie,SmoothColliesMutationdescribedinarticle(Parker,Heidi2007)Hokkaido Mutationdescribedinarticle. (Mizukami,Keijiro2012)SilkenWindhound Noarticlefoundaboutthemutation ConeDegeneration(CD)GermanShorthairedPointer,Alaskanmalamute, Mutationdescribedinarticle

(Sidjanin,Duska2002) AustralianShepherd,MiniatureAustralianShepherdNoarticlefoundaboutthemutationConeRodDystrophy2(CRD2) AmericanPitbullTerrier,AmericanStaffordshireTerrierMutationdescribedinarticle.

(Goldstein,Orly2013)PitbullTerrier Noarticlefoundaboutthemutation ConeRodDystrophy3(CRD3)GlenofImaalTerrier Mutationdescribedinarticle.(Goldstein,Orly2010)ConeRodDystrophy4-PRA(CRD4-PRA) Dachshund NoarticlefoundaboutthemutationCone-RodDystrophy1-PRA(Cord1-PRA) Dachshund Mutationdescribedinarticle(Miyadera,Keiko2009)EnglishSpringerSpanielMutationdescribedinarticle (Downs,Louise2014)Papillion,CurlyCoatedRetriever NoarticlefoundaboutthemutationCongenitalstationarynightblindness(CSNB) Briard Mutationdescribedinarticle (Aguirre,1998)

Dryeyecurlycoatsyndrome(CCS) CavalierKingCharlesSpaniel Mutationdescribedinarticle (Forman,Oliver2012)

52

HereditaryCataract(HC) AustralianShepherd Mutationdescribedinarticle (Mellersh,Cathryn2006)FrenchBulldog,Wäller,MiniatureAustralianShepherdNoarticlefoundaboutthemutationHereditaryCataract2(HSF4) BostonTerrier, StaffordshireBullTerrierMutationdescribedinarticle(Mellersh,Cathryn2006)Primarylensluxation(PLL) AustralianCattleDog,ChineseCrestedDog,MiniatureBullTerrier,JackRussellTerrier,JagdTerrier,LancashireHeeler,,ParsonRussellTerrier,PatterdaleTerrier,RatTerrier,SealyhamTerrier,TenterfieldTerrier,TibetanTerrier,ToyFoxTerrier,VolpinoItaliano,WelshTerrier,Whire-hairedFoxTerrier,YorkshireTerrier

Mutationdescribedinarticle(Gould,David2011)AmericanEskimoDog,AmericanHairlessTerrier,ChineseFooDog,FoxTerrier,LakelandTerrier,LucasTerrier,NorfolkTerrier,NorwichTerrier,Pug,TeddyRooseveltTerrier,WestphaliaTerrier. NoarticlefoundaboutthemutationPrimaryopenangleglaucoma(POAG) Beagle Mutationdescribedinarticle (Olson,LanaM2011)ProgressiveRetinalAtrophy(prcdPRA) Maltipoo,AustralianSilkyTerrier,BolonkaZwetna,EnglishShepherd,GermanSpitz,GiantSchnauzer,Schipperke NoarticlefoundaboutthemutationAmericanCockerSpaniel,AmericanEskimoDog,AustralianCattleDog,AustralianShepherd,AustralianStumpyTailCattleDog,ChesapeakeBayRetriever,ChineseCrestedDog,Cockapoo,DwarfPoodle,EnglishCockerSpaniel,EntlebucherMountainDog,FinnishLapphund,GoldenRetriever,KarelianBeardog,Kuvasz,LabradorRetriever,LapponianHerder,Markiesje,MiniatureAustralianShepherd,MiniaturePoodle,MoyenPoodle,NorwegianElkhound,NovaScotiaDuckTollingRetriever,Poodle,PortugueseWaterDog,SilkyTerrier,SpanishWaterDog,SwedishLapphund,ToyPoodle,YorkshireTerrier Mutationdescribedinarticle(Zangerl,Barbara2006)ProgressiveRetinalAtrophy(Dominant-PRA) BullMastiff,EnglishMastiff Mutationdescribedinarticle.(Downs,Louise2014)ProgressiveRetinalAtrophy(BasenjiPRA) Basenjis Mutationdescribedinarticle(Goldstein,Orly2013)ProgressiveRetinalAtrophy(gPRA) Schapendoes Mutationdescribedinarticle(Downs,Louise2014)ProgressiveRetinalAtrophy(GRPRA1) GoldenRetriever Mutationdescribedinarticle(Downs,Louise2014)ProgressiveRetinalAtrophy(GRPRA2) GoldenRetriever Mutationdescribedinarticle(Downs,Louise2014)ProgressiveRetinalAtrophy(IGPRA1)ItalianGreyhound Noarticlefoundaboutthemutation ProgressiveRetinalAtrophy(rcd1PRA)IrishSetters Mutationdescribedinarticle(Downs,Louise2014)Sloughi Mutationdescribedinarticle(Dekomien,G2000)ProgressiveRetinalAtrophy(rcd2PRA) FarmCollie,RoughCollies,SmoothColliesMutationdescribedinarticle(Kukekova,AnnaV2009)ProgressiveRetinalAtrophy(rcd3PRA) CardigenWelshCorgi,ChineseCrestedDog Mutationdescribedinarticle(Petersen-Jones,SM1999)WelshCorgi Noarticlefoundaboutthemutation

53

ProgressiveRetinalAtrophy(rcd4PRA) AustralianCattleDog,LlewellinSetter,PolishLowlandSheepdog,SmallMunsterlanderNoarticlefoundaboutthemutation.Englishsetter Noarticlefoundaboutthemutation.Gordonsetter,IrishSetters Mutationdescribedinarticle(Downs,2013)Tibetanterrier Mutationdescribedinarticle.(Downs,Louise2014)ProgressiveRetinalAtrophy(TypeAPRA) MiniatureSchnauzer Mutationdescribedinarticle(Downs,Louise2014)ProgressiveRetinalAtrophy1(Pap-PRA1) Papillion,Phalene Mutationdescribedinarticle(Ahonen,Saija2013)ProgressiveRetinalAtrophy1(XLinkedPRA1)Samoyed,SiberianHusky Mutationdescribedinarticle(Zhang,Qi2002)RetinalDysplasiaRetinalFoldsOculoSkeletalDysplasia(RD+OSD)1 LabradorRetriever,Samoyed Mutationdescribedinarticle (Goldstein,Orly2010)

54

Appendix 4

CardiovascularsystemandblooddisordersTable5DefinitivelistforgoodDNAtests

Disease Breed Bleeding disorder due to P2RY12

defect GreatSwissMountainDog

Cycl ic Neutropenia (CN) ColliesFactor VI I - Defic iency Beagle

Haemophil ia B (Factor IX def ic iency)

Rhodesianridgeback

AiredaleTerrier BullTerrier

Germanwirehairedpointer LhasaApso

Macrothrombocytopenia (MTC) Boxer CavalierKingCharlesSpaniel

Polycythemia Maltese Poodle

YorkshireTerrier WestHighlandWhiteTerrier

Thrombasthenia Otterhound Thrombasthenia 2 PyreneeseBerghond

Thrombopathia Basset AmericanEskimoDog

LandseerVon-Wil lebrands Disease Type 2 GermanWirehairedPointerVon-Wil lebrands Disease Type 3 DutchKooiker

ScottishTerrier ShetlandSheepdog

Metabolicandimmunediseases

Table6DefinitivelistforgoodDNAtests

Disease Breed C3 Defic iency BrittanySpaniel

Canine Leukocyte Adhesion Defic iency (CLAD), Type 1

IrishSetters

Canine Leukocyte Adhesion Defic iency (CLAD), Type 3

Germanshepherd

Cobalamin Malabsorption/cubi l in def ic iency Beagle BorderCollie

Congenital Hypothyreosis (CHG) 2 TenterfieldTerriërCopper toxicosis BedlingtonTerriers

Fucosidosis EnglishspringerspanielGlycogen Storage Disease Type l (GSD I) MalteseGlycogen Storage Disease GSD Type I I Ia

(GSDII Ia) CurlyCoatedRetrievers

Ivermectin hypersensit iv ity (MDR1 gene defect)

AustralianShepherd

Collies

55

BorderCollie ShetlandSheepdog WhiteShepherd

GermanShepherd LonghairedWhippet

SilkenWindhoundMucopolysaccharidose Type VI I - 2 BrazilianTerrier

Mucopolysaccharidosis Type VI I GermanShepherdMucopolysaccharidosis Type I I Ia Dachshund

Phosphofructokinase defic iency (PFKD) AmericanCockerSpaniel GermanSpaniel Whippet

EnglishSpringerSpaniel Prekal l ikrein defic iency ShihTzu

Pyruvate Dehydrogenase Phosphatase 1 (PDP1)

ClumberSpaniel,SussexSpaniel

Pyruvate k inase Defic iency (PKDef) Basenjis CairnTerrier

WesthighlandWhiteTerrier LabradorRetriever Type2Pug Type3Beagle

Severe combined Immunodefic iency (X- l inked-SCID)

Basset

WelshCorgiSevere combined Immunodefic iency (SCID) JackRussellTerrier

Severe combined Immunodefic iency 2(SCID2) FrisianWaterDogs Trapped Neutrophi l Syndrome (TNS) BorderCollieVitamin D-defic iency r ickets, type I I Pomeranian

Glycogen storage disease type I I (Pompe Disease)

LapponianHerder

SwedishLapphund

EyediseasesTable7DefinitivelistforgoodDNAtests

Disease BreedAlbinism(White) DobermanPincher

CanineMulti-focalRetinopathy(CMR) AustralianShepherd Boerboel

GreatPyrenees Mastiffs

CanineMulti-focalRetinopathy(CMR2) CotondeTulearCollieEyeAnomalie(CEA) AustralianShepherd

BeardedCollie BorderCollie

BoykinSpaniel Hokkaido LancashireHeeler NovaScotiaDuckTollingRetriever Sheepdog ShetlandSheepdog Whippet Collies LonghairedWhippet

56

MiniatureAustralianShepherd RoughCollies SmoothCollies

ConeDegeneration(CD) GermanShorthairedPointer Alaskanmalamute

ConeRodDystrophy2(CRD2) AmericanPitbullTerrier AmericanStaffordshireTerrier

ConeRodDystrophy3(CRD3) GlenofImaalTerrier Cone-RodDystrophy1-PRA(Cord1-PRA) Dachshund

EnglishSpringerSpanielCongenitalstationarynightblindness(CSNB) Briard

Dryeyecurlycoatsyndrome(CCS) CavalierKingCharlesSpaniel HereditaryCataract(HC) AustralianShepherd

HereditaryCataract2(HSF4) BostonTerrier StaffordshireBullTerrier

Primarylensluxation(PLL) AustralianCattleDog ChineseCrestedDog MiniatureBullTerrier

JackRussellTerrier JagdTerrier

LancashireHeeler ParsonRussellTerrier PatterdaleTerrier RatTerrier SealyhamTerrier TenterfieldTerrier TibetanTerrier ToyFoxTerrier VolpinoItaliano WelshTerrier Whire-hairedFoxTerrier YorkshireTerrier

Primaryopenangleglaucoma(POAG) BeagleProgressiveRetinalAtrophy(prcdPRA) AmericanCockerSpaniel

AmericanEskimoDog AustralianCattleDog

AustralianShepherd AustralianStumpyTailCattleDog ChesapeakeBayRetriever

ChineseCrestedDog Cockapoo

DwarfPoodle EnglishCockerSpaniel EntlebucherMountainDog FinnishLapphund GoldenRetriever KarelianBeardog Kuvasz LabradorRetriever LapponianHerder Markiesje MiniatureAustralianShepherd MiniaturePoodle MoyenPoodle NorwegianElkhound NovaScotiaDuckTollingRetriever Poodle

57

PortugueseWaterDog SilkyTerrier SpanishWaterDog SwedishLapphund ToyPoodle YorkshireTerrier

ProgressiveRetinalAtrophy-Dominant-(PRA) BullMastiff EnglishMastiff

ProgressiveRetinalAtrophy(gPRA) Schapendoes ProgressiveRetinalAtrophy(GRPRA1) GoldenRetrieverProgressiveRetinalAtrophy(GRPRA2) GoldenRetrieverProgressiveRetinalAtrophy(rcd1PRA) IrishSetters

Sloughi ProgressiveRetinalAtrophy(rcd2PRA) FarmCollie

RoughCollies SmoothCollies

ProgressiveRetinalAtrophy(rcd3PRA) CardigenWelshCorgi ChineseCrestedDog

ProgressiveRetinalAtrophy(rcd4PRA) Gordonsetter IrishSetters

TibetanterrierProgressiveRetinalAtrophy(TypeAPRA) MiniatureSchnauzer ProgressiveRetinalAtrophy1(Pap-PRA1) Papillion,

PhaleneProgressiveRetinalAtrophy1(XLinkedPRA1) Samoyed

SiberianHusky

RetinalDysplasiaRetinalFoldsOculoSkeletalDysplasia(RD+OSD)1

LabradorRetriever

Samoyed

58

Appendix 5 ThemailsenttotheLaboratories

AnswerfromOptiGen

59

AnswerfromVetGen

60

AnswerfromLaboklin

the reliability of dna tests for inherited diseases

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