ManagementofWagyuRecessiveGeneticConditionsThescientifictermsforthetwomostcommonmodesofgeneticinheritanceare:autosomaldominantandautosomalrecessive.ThetermAutosomalmeansthattheconditionortraithasageneticbasis(controlledbygenes).Withcattlebreedingasingleallele(copyofagene)comesfromeachparentforthesevenbilliongenesinthecattlegenome.Autosomaldominantdescribesatraitorconditionthatisexpressedwhenonlyasingleallele(copyofagene)ispresent.Apracticalexampleofthisisthetraitofblackcoatcolour.Onlyoneparentisrequiredtoinputthedominant“blackcoatcolour”alleletohavearesultantblackcolouredcalf.Autosomalrecessivedescribesatraitorconditionthatisexpressedwhentwoallelesarepresent(onefromeachparent).Twocopiesoftherecessiveallelearerequiredasanimalscarryingonlyonecopyoftherecessivealleledonotexhibitthetrait(Carriers).ApracticalexampleofthisistherecessiveconditionCL16.Animalswithonecopyoftherecessiveallele(Carriers)shownodiseasesymptomsandappearnormal.OnecopyoftherecessiveallelemustbepresentfrombothparentstoshowsymptomsofCL16disease.Twocopiesoftherecessiveallelemustbepresentbeforeananimalshowssymptomsoftherecessivedisease(Affectedanimal).Carriersappearphenotypically(observablecharacteristics)normalandareindistinguishablefromnon-carriers(Freeanimals)unlessgenetictestingisperformed.Freeanimalsinheritthenormalgenefrombothparents.PleaseNotethattheimportanceofrecessivetestingistoidentifycarriersthatmaybeusedasbreeding stock. If carrier sires are used as a terminal cross, the impact of harmful recessiveconditions is diminished (assuming the breeding herd is a non-carrier or free (F) status) as itwouldbeexpectedthatallprogenyisslaughtered.

ReportedWagyuRecessiveConditionsChediakHigashiSyndrome(CHS)statusCHSisamacrophagedisorder(awhitebloodcellthathasanimportantroleintheimmuneresponsetodisease).Ifcattlehaveamalfunctioningimmunesystem,thismakesthemunabletoresistbacterialchallenge.Bloodisslowtocoagulatesooftenthefirstindicatorisunusualumbilicalcordhaemorrhageatparturition(calving).Cattlewiththissyndromeoftenhaveanunusuallypalecoatcolour.Photograph–Affectednewborncalfwithapalecoat

Spherocystosis(B3)statusThisisadisorderofthesurfacemembraneoftheerythrocyte(redbloodcells).TheproteinfromtheB3genemakesupthebasicstructureoftheerythrocyte.Cattlethatarehomozygous(havetwocopiesoftherecessiveallele)haveperniciousanaemia(bleedingcausedbytheabnormalredbloodcells).Deathnormallyoccurswithinthefirst7daysafterbirth.Somecaseslivetoadulthoodbutthereisasevereretardationingrowth.Photographs-Icterusintheeyes&anaemiccalf@5m(90kg)

Claudin16deficiency(CL16)status(Type1)Claudin16orRTD(Renaltubulardysplasia)isagenedisorderonchromosome1andcauseskidneyfailure(chronicinterstitialnephritis(CIN),oftenwithzonalfibrosisorexcessoffibrousconnectivetissue.Thereare2typesofthedeletioninthisgenethatcancauseCIN.Thisdisorderresultsinterminalkidneyfailureandtheonsetcanoccuranytimefromlateadolescence.Cattleareunlikelytolivemorethan6years.Photograph-ElongatedHoovesonanAffectedCL16

Factor13deficiency(F13)statusThisgenecontributestofibrinstability,whichisanintegralpartofthebloodcoagulationpathway(bloodclottingability).Disordersinthisgenecauseseverehaemorrhage(bleeding).Incalves,haemorrhageisparticularlylikelytooccurinthehindquarterscausingbloodtopoolandstagnateunderthehide.Inadult

cattleanyminortrauma(suchashittingtheanimal)cancausemajorhaemorrhageatthetraumasite.NotethatnoF13CarriershavebeenidentifiedinthetestedUSWagyupopulation.Photograph-NavelofanAffectedF13newborn

FactorXIdeficiency(F11)status(usuallynon-lethal)FactorXI(F11)isaplasmaproteinthatparticipatesintheformationofbloodclots.FactorXIdeficiencyisanautosomaldisorderthatisassociatedwithmildbleedinginWagyu.Affectedanimalsshowprolongedbleedingtimeandabnormalplasmacoagulationaftertraumaorsurgicalproceduressuchascastrationordehorning.Photograph–AffectedF11Femaleexhibitingnoharmfulsymptoms

*Photosource–ColorAtlasofBovineCongenitalDefects(Ed.K.Hamana:2006),GRS

RecessiveGeneStatusDNAtestsreportthestatusofanimalusingthree(3)categories

Free indicates that the sample submitted for this animal has beenfound to be clearof the causative mutation (abnormal gene)responsible for an identified autosomal condition. This animal ishomozygousfree,meaningthatithastwocopiesofthenormalallele.

Carrierindicatesthattheanimalhasbeenfoundtohaveonecopyofthe causative mutation responsible for an identified autosomalcondition.Thisanimalisheterozygousforthemutation,meaningthatit has one abnormal allele and one normal allele. This animal couldpass the mutation (abnormal gene) to approximately half of itsprogeny.Affectedcalvesarehomozygousforthemutationresponsiblefortheautosomalconditionandhavetwocopiesoftheabnormalvariantofthegene.*Note that while unusual, some Affected (A) animals will reachbreedingageandproduceoffspring

Whatdoesthismeanformanagementofthegeneticconditions?Asonegenecomesfromeachparent;expectedprogenyresultsofbreedingdifferentgeneticconditionstatussires&damsarelistedintableformatbelowFigure150%FREESIRE/FREEDAM

FREE100%FREE100%FREE100%FREE100%

50%CARRIERSIRE/FREEDAM

CARRIER50%CARRIER50%FREE50%FREE50%

50%CARRIERSIRE/CARRIERDAM

AFFECTED25%CARRIER50%CARRIER50%FREE25%

50%AFFECTEDSIRE/FREEDAM

CARRIER100%CARRIER100%CARRIER100%CARRIER100%

50%AFFECTEDSIRE/CARRIERDAM

AFFECTED50%CARRIER50%CARRIER50%AFFECTED50%

50%AFFECTEDSIRE/AFFECTEDDAM

AFFECTED100%AFFECTED100%AFFECTED100%AFFECTED100%

DealingwithrecessiveconditionsUnlikediseasesthataretheresultofpathogenicagentssuchasbacteriaorvirusesthatmayresultinheavylossesofanimalsandmajorde-contaminationprocedures,geneticconditionsarenotcontagiousandCANNOTbetransmittedmerelybyanimal-to-animalcontact.Controlofgeneticconditionsrequiresgoodmanagementpractices.Thesearedevelopedbasedontheaimsandobjectivesofeachenterprise.Controlofgeneticconditionsrequiresgoodmanagementpractices.ManagementOptionsForWagyuRecessiveConditionsAnimalswithaknowncarrierstatuscanbeusedforbreeding.However,follow-uptestingofallprogenywouldbeessentialtodevelopfuturebreedingstrategies.WhenusingCarrieranimalsforbreeding,youcanexpectapproximately50%oftheprogenytobeCarriersforthatparticularcondition.Carrieranimalscanbeculled,separatedorusedwithcare.TheremainingprogenywillbeFreeanimalsandcanbeusedtoperpetuatetheherd.ContinuedbreedingbyjoiningtwoCarrieranimalswiththesameconditionisnotrecommendedduetotheriskofproducingAffectedanimals.Theimportantthingtorememberwithautosomalrecessiveconditionsisthattheyareachallengetobemanagedandnotfeared.Manymanagementoptionsexistforthecontrolofgeneticconditionsandtheseareformulatedbasedontheindividualneedsandrequirementsofeachenterprise.Someoftheseinclude:

• TestallanimalsandremoveCarriers.

• TestallanimalsanduseCarriersONLYinterminalbreedingprograms.

• TestsiresandonlyuseFreebullsforbreeding.

• UseCarriersforbreedingONLYonFreeanimals.Testallprogeny.

• UseCarriersforbreedingonanimalsthatareFreeofthesamecondition.(Example–UseF11CarriersonF11Freeanimals).

Whataboutcross-breeds?Recessiveconditionscanbeperpetuatedincross-breeds.FirstcrossesareunlikelytoproduceanyAffectedprogeny(unlessbothbreedshavethesamecondition).Subsequentinter-breedingofcross-bredanimalsmayproduceadditionalCarriersandAffectedanimals.Canyouretainsuperiorproductiongeneticsfromcarrieranimals?

Yes!Carriersiresanddamscanbeusedforbreeding.However,follow-uptestingofallprogenyisessentialforfuturebreedingstrategieswiththatprogeny.Expect50%oftheirprogenytobeCarriers.TheseCarrierscanbeidentifiedbytesting.BreedingbyjoiningtwoCarriers(withthesamecondition)isnotrecommendedduetotheriskofproducingAffectedanimals.Source:1.Marsh,IandGalea,F-IndustryandInvestment,NSWElizabethMacarthurAgriculturalInstitute(EMAI)Australia2.Hirayama,H.,S.Kageyama,S.Moriyasu,T.Hirano,Y.Sugimoto,N.Kobayashi,M.Inaba,K.Sawai,S.Onoe,andA.Minamihashi.2004.Geneticdiagnosisofclaudin-16defciencyandsexdeterminationinbovinepreimplantationembryos.JReprodDev50:613-8.2.Kageyama,S.,H.Hirayama,S.Moriyasu,M.Inaba,D.Ito,H.Ohta,K.Sawai,A.Minamihashi,andS.Onoe.2006.Geneticdiagnosisofband3deficiencyandsexinginbovinepreimplantationembryos.JVetMedSci68:319-23.3.Kunieda,M.,T.Tsuji,A.R.Abbasi,M.Khalaj,M.Ikeda,K.Miyadera,H.Ogawa,andT.Kunieda.2005.AninsertionmutationofthebovineFiigeneisresponsibleforfactorXIdefciencyinJapaneseblackcattle.MammGenome16:383-9.4.Kunieda,T.,M.Nakagiri,M.Takami,H.Ide,andH.Ogawa.1999.CloningofbovineLYSTgeneandidentifcationofamissensemutationassociatedwithChediak-Higashisyndromeofcattle.MammGenome10:1146-9.