Anth 4234, 4-4-18 - University of...
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ANTH 4234, DRD4, a hypervariable gene. • “One of the most extensively studied polymorphisms in psychiatric and behavioral genetics… . The first gene polymorphism associated with a human personality trait, Novelty Seeking .” (Sweitzer, 2013)(emphasis added)
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Transcript of Anth 4234, 4-4-18 - University of...
ANTH4234,DRD4,ahypervariablegene.• “Oneofthemostextensivelystudiedpolymorphismsinpsychiatricandbehavioralgenetics….Thefirstgenepolymorphismassociatedwithahumanpersonalitytrait,NoveltySeeking.”(Sweitzer,2013)(emphasisadded)
NEURONS:apartofthestuffofthought;86billioninhumanbrain,250billioninelephantbrain.
SYNAPTICCLEFT
ExonIIIcodesthesynthesisofthethirdintracellularloopofType2DopamineReceptors
From86billionneuronstoatrillionconnections
WHENMANYNEURONSCOMMUNICATE,ANEURALNETWORKFORMS,SUCHASTHEMOTIVATIONALVALUEANDLEARNINGNETWORKINPRIMATES.
DRD4(EXONIII)ISAVARIABLENUMBERTANDEMREPEAT(VNTR)GENE.REPEATLENGTHIS16AMINOACIDS/48NUCLEOTIDES.
MOST,PERHAPSALL,MAMMALIANGENOMESINCLUDEDRD4
MANY,PERHAPSALL,PRIMATEGENOMESINCLUDEDRD4ASAVNTR,WITHANYNUMBERFROM2TO11REPEEATS
DRD4ALLELICVARIATONANDBEHAVIORALVARIATIONINVERVETS
MOREREPEATS=MORENOVELTYSEEKING?(7REPEATRECEPTOR<SENSITIVETHAN4REPEAT)
• 100’sofstudiesexploring4rv7r.• 7r’slikenovelty.• 7r’stakegreaterrisks.• 7r’shavehightimepreferencewhenassociatedwithlowchildhoodSES.• 7r’shavehighersocialityinchildrenwithgoodparenting• Lowerwithbadparenting.• 7r’shavemoresexualpartners.• 7rHealthierinnomadicgroups,notashealthyinpastoral.• MoreDisorganizedAttachmentDisorderfor7rthan4r.• MoresevereADHDfor7rthan4r.
WORLDWIDEDISTRIBUTIONOFDRD4REPEATALLELESINHUMANS.• LESS7RDIVERSITYINAFRICA,LESSLDFOR7RINAFRICA=SELECTION,BOTTLENECK,DRIFT?• Highfrequencyof7RinAmericas• BigstudyofkidswithADHD,noassociationw/repeat,butassociationwithrarehaplotypes.
NOVELTYSEEKERSLIKENEWPLACES?NOVELTYSEEKERSDOWELLINNEWPLACES?IsitaGroupdifference?Isitdrift?
Morethanrepeats– morethan35haplotypes.Apatternofselection?(Ding,2002)
TECHNICALPROBLEMSANDHOWCANREPEATSALTERBEHAVIOR?
APATTERNCONSISTENTWITHDRIFT,NOTSELECTION?Kiddchangesstripes.(Kidd,2014)
CONCLUSIONS
•DRD4GROUPVARIABILITYEFFECT=NOTYET,MAYBENEVER,MAYBETOMORROW.•DRD4INDIVIDUALVARIABILITYEFFECT=PROBABLY,GENEXENVIRONMENT.•WHOREALLYKNOWS?•MOREWORKNEEDED.
Forthoseinterestedinmore:
• Bomberg-Martin,DopamineinMotivationalControl:Rewarding,AversiveandAlerting,NeuronVol.68,pp815-835,2010.
• Bailey,J.N.,TheassociationofDRD4andnoveltyseekingisfoundinanonhumanprimatemodel.PsychiatricGenetics,17(17),23–2723,2007.
• Matsumoto,Twotypesofdopamineneurondistinctlyconveypositiveandnegativemotivationalsignals.Nature,459(7248),837–841,2009.
• Sweitzer,PolymorphicvariationinthedopamineD4receptorpredictsdelaydiscountingasafunctionofchildhoodsocioeconomicstatus:Evidencefordifferentialsusceptibility.SocialCognitiveandAffectiveNeuroscience,8(5),499–508,2013.
• Ding,EvidenceforPositiveSelectionActingattheHumanD4ReceptorLocus, PNAS,Vol.99,No1,308-314,2002.
• Kidd,Anhistoricalperspectiveon“Theworldwidedistributionofallelefrequenciesatthehumandopaminereceptorlocus.” HumanGentics,133,431-433,2014.
