Genomic Imprinting - Learn Genetics-Utah

An individual normally has one active copy of an imprinted gene. Improper imprinting can result in an individual having two active copies or two inactive copies ... DonateHomeEpigeneticsGenomicImprintingGenomicImprintingWhatIsImprinting?Formostgenes,weinherittwoworkingcopies--onefrommomandonefromdad.Butwithimprintedgenes,weinheritonlyoneworkingcopy.Dependingonthegene,eitherthecopyfrommomorthecopyfromdadisepigeneticallysilenced.Silencingusuallyhappensthroughtheadditionofmethylgroupsduringeggorspermformation.Theepigenetictagsonimprintedgenesusuallystayputforthelifeoftheorganism.Buttheyareresetduringeggandspermformation.Regardlessofwhethertheycamefrommomordad,certaingenesarealwayssilencedintheegg,andothersarealwayssilencedinthesperm.ImprintedGenesBypassEpigeneticReprogrammingSoonaftereggandspermmeet,mostoftheepigenetictagsthatactivateandsilencegenesarestrippedfromtheDNA.However,inmammals,imprintedgeneskeeptheirepigenetictags.Imprintedgenesbegintheprocessofdevelopmentwithepigenetictagsinplace.Imprintedgenesarenottheonlygenesthatbypassepigeneticreprogrammingintheearlyembryo.Studyingimprintingmayhelpresearchersunderstandhowothergenesmakeitthroughreprogrammingwithoutlosingtheirepigenetictags.LEARNMORE:EPIGENETICSANDINHERITANCEImprintingisuniquetomammalsandfloweringplants.Inmammals,about1%ofgenesareimprinted.ImprintingisrequiredfornormaldevelopmentAnindividualnormallyhasoneactivecopyofanimprintedgene.Improperimprintingcanresultinanindividualhavingtwoactivecopiesortwoinactivecopies.Thiscanleadtoseveredevelopmentalabnormalities,cancer,andotherproblems.Prader-WilliandAngelmansyndromearetwoverydifferentdisorders,buttheyarebothlinkedtothesameimprintedregionofchromosome15.Someofthegenesinthisregionaresilencedintheegg,andatleastonegeneissilencedinthesperm.Sosomeonewhoinheritsadefectonchromosome15ismissingdifferentactivegenes,dependingonwhetherthechromosomecamefrommomordad.Prader-Willisyndrome•Symptomsincludelearningdifficulties,shortstature,andcompulsiveeating.•Individualsaremissinggeneactivitythatnormallycomesfromdad.•Happenswhendad'scopyismissing,orwhentherearetwomaternalcopies.Angelmansyndrome•Symptomsincludelearningdifficulties,speechproblems,seizures,jerkymovements,andanunusuallyhappydisposition.•Individualsaremissinggeneactivitythatnormallycomesfrommom.•Happenswhenmom'scopyisdefectiveormissing,orwhentherearetwopaternalcopies.TheDifficultyofCloningMammalsMammalsarenotoriouslydifficulttoclone.Researchersoftenneedtogothroughthecloningproceduredozensorevenhundredsoftimesinordertoproduceasinglehealthyclone.Theepigenome,includingproblemswithimprintedgenes,islikelytobeattherootofthisdifficulty.Themostcommonmethodofcloningiscalledsomaticcellnucleartransfer(SCNT).SCNTinvolvesremovingadonornucleusfromanon-reproductivecell(oftenaskincellormammarycell)andplacingitintoaneggcellthathashaditsnucleusremoved.Cloneshaveabnormalepigenomes,whichcanleadtoavarietyofproblems.Theepigeneticproblemswithcloneslikelyarisefortworeasons.First,thedonornucleuscomesfromadifferentiatedcellwithepigenetictagsalreadyinplace.Thesetagskeepgenesswitchedonoroffandallowthecelltoperformitsresponsibilities.Afterthedonornucleusistransferred,theeggdoesitsbesttoerasetheepigenetictags.Buttheprocessisfaulty,delayedandincomplete.Second,theepigenetictagsinthedonornucleushavebeencopiedseveraltimesover.WhilethemachinerythatcopiestheDNAcodeisfaithful(itmakesaboutoneerrorinhalfabillion),theepigeneticcopyingmachineryissloppy.Insomecases,itserrorratecanbeashighas1in25.Miscopiedepigenetictagsonevenaverysmallnumberofimprintedgenesinthedonornucleuscouldhaveseriousconsequencesduringthedevelopmentoftheresultingembryo.Dollythesheepwasthefirstmammaltobeclonedbysomaticcellnucleartransfer(SCNT).LearnmoreaboutSCNTinClickandCloneWhyImprint?TheGeneticConflictHypothesisScientistshavecomeupwithanumberofhypothesestoexplainwhyimprintinghappensinmammals.Oneofthese,theGeneticConflicthypothesis,supposesthatimprintinggrewoutofacompetitionbetweenmalesformaternalresources.Insomespecies,morethanonemalecanfatheroffspringfromthesamelitter.Ahousecat,forexample,canmatemorethanonceduringaheatandhavealitterofkittenswithtwoormorefathers.Ifonefather'skittensgrowlargerthantherest,hisoffspringwillbemorelikelytosurvivetoadulthoodandpassalongtheirgenes.Soit'sintheinterestofthefather'sgenestoproducelargeroffspring.Thelargerkittenswillbeabletocompeteformaternalresourcesattheexpenseoftheotherfather'skittens.Ontheotherhand,abetteroutcomeforthemother'sgeneswouldbeforallofherkittenstosurvivetoadulthoodandreproduce.Themotheralonewillprovidenutrientsandprotectionforherkittensthroughoutpregnancyandafterbirth.Sheneedstobeabletodivideherresourcesamongseveralkittens,withoutcompromisingherownneeds.Itturnsoutthatmanyimprintedgenesareinvolvedingrowthandmetabolism.Paternalimprintingfavorstheproductionoflargeroffspring,andmaternalimprintingfavorssmalleroffspring.Oftenmaternallyandpaternallyimprintedgenesworkintheverysamegrowthpathways.Thisconflictofinterestsetsupanepigeneticbattlebetweentheparents--asortofparentaltug-of-war.Beckwith-WiedemannSyndromeTheIgf2gene(butnottheIgf2receptorgene)isalsoimprintedinhumans.TheIgf2genecodesforahormonethatstimulatesgrowthduringembryonicandfetaldevelopment.MethyltagsnormallysilencethematernalIgf2gene.ButaDNAmutationoran"epimutation"(missingmethyltags)canactivateit,resultingintwoactivecopiesofthegene.ActivationofthematernalIgf2geneduringeggformationorveryearlyindevelopmentcausesBeckwith-WiedemannSyndrome(BWS).WhilechildrenwithBWShaveavarietyofsymptoms,themostcommonandobviousfeatureisovergrowth.BabieswithBWSarebornlargerthan95%oftheirpeers.Theyalsohaveanincreasedriskofcancer,especiallyduringchildhood.BWSoccursonceinabout15,000births.However,inbabiesthatwereconceivedinthelaboratorywiththehelpofartificialreproductivetechnology(ART),therateofBWSmaybeashighas1in4,000.ThisandotherevidenceofimprintingerrorsispromptingsometocallforfurtherinvestigationintothesafetyofcommonARTlaboratoryprocedures.LigersandTigonsImprintedgenesareundergreaterselectivepressurethannormalgenes.Thisisbecauseonlyonecopyisactiveatatime.Anyvariationsinthatcopywillbeexpressed.Thereisno"back-upcopy"tomaskitseffects.Asaresult,imprintedgenesevolvemorerapidlythanothergenes.Andimprintingpatterns--whichgenesaresilencedintheeggsandsperm--alsoevolvequickly.Theycanbequitedifferentincloselyrelatedspecies.Lionsandtigersdon'tnormallymeetinnature.Buttheycangetalongverywellincaptivity,wheretheysometimesproducehybridoffspring.Theoffspringlookdifferent,dependingonwhothemotheris.Amalelionandafemaletigerproducealiger-thebiggestofthebigcats.Amaletigerandafemalelionproduceatigon,acatthatisaboutthesamesizeasitsparents.Thedifferenceinsizeandappearancebetweenligersandtigonsisdueinparttotheparents'differentlyimprintedgenes.Otheranimalscanalsohybridize,withsimilarresults.Forexample,ahorseandadonkeycanproduceamuleorahinny.Imprintingpatternsoftendifferevenincloselyrelatedanimalssuchastigersandlions.ImprintedGenesareSensitivetoEnvironmentalSignalsImprintedgenesareespeciallysensitivetoenvironmentalsignals.Becauseimprintedgeneshaveonlyasingleactivecopyandnoback-up,anyepigeneticchangesor"epimutations"willhaveagreaterimpactongeneexpression.Environmentalsignalscanalsoaffecttheimprintingprocessitself.Imprintinghappensduringeggandspermformation,whenepigenetictagsareaddedtosilencespecificgenes.Diet,hormonesandtoxinscanallaffectthisprocess,impactingtheexpressionofgenesinthenextgeneration.ReferencesReferencesJaenisch,R.(1997).DNAmethylationandimprinting:whybother?TrendsinGenetics,13(8):323-329(subscriptionrequired).Murrell,A.etal.(2008).DistinctmethylationchangesattheIGF2-H19locusincongenitalgrowthdisordersandcancer.PLoSOne,3(3):e1849)geneimprint-InformationaboutimprintingandarunninglistofimprintedgenesinmouseandhumansImprintingdisordersandART:world'slargeststudyresultsarereassuring.Bio-MedicineOnlinearticlesummarizingaresearchstudyofBeckwith-WiedemannSyndromeandArtificialReproductiveTechnology.Bowdin,S.etal.(2007).Asurveyofassistedreproductivetechnologybirthsandimprintingdisorders.HumanReproduction,22(12):3237-3240.APAformat:GeneticScienceLearningCenter.(2013,July15)GenomicImprinting. RetrievedDecember25,2021,fromhttps://learn.genetics.utah.edu/content/epigenetics/imprinting/CSEformat:GenomicImprinting[Internet].SaltLakeCity(UT):GeneticScienceLearningCenter;2013 [cited2021Dec25]Availablefromhttps://learn.genetics.utah.edu/content/epigenetics/imprinting/Chicagoformat:GeneticScienceLearningCenter."GenomicImprinting."Learn.Genetics. July15,2013.AccessedDecember25,2021.https://learn.genetics.utah.edu/content/epigenetics/imprinting/.