autism genes 2005r
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N I C H DEuniceKennedyShriverNational InstituteofChildHealthandHumanDevelopment
AutismResearchattheNICHD
U.S.DEPARTMENT OF HEALTHAND HUMAN SERVICESNational InstitutesofHealth
AutismandGenesTheEuniceKennedyShriverNationalInstituteofChildHealthandHumanDevelopment(NICHD),part
of
the
National
Institutes
of
Health
(NIH),
within
the
U.S.DepartmentofHealthandHumanServices,isoneofmanyfederalagenciesdoingresearchonautism,includingitspossiblecauses.In1997,theNICHDandtheNationalInstituteonDeafnessandOtherCommunicationsDisorders(NIDCD)startedtheNetworkontheNeurobiologyandGeneticsofAutism:CollaborativeProgramsofExcellenceinAutism(CPEA).ResearchersinthisNetworkworktounderstandwhichgenesmightbeinvolvedinautismandhowgenesplayaroleinthecondition. Workingwithotherscientistsaroundtheworld,theCPEAresearchershavealreadylearnedagreatdealaboutautismandgenes.Whataregenes?GenesarepiecesofDNA,materialthatcontainsalltheinformationneededtobuildaperson. Genesarehereditary,meaningparentspassgenesontotheirchildren.Mostgeneticmaterialisfoundinthenucleusofacell,astorageareathatkeepsthesematerialstogetherinoneplace. Thenucleusstoresgeneticmaterialsinpackagescalledchromosomes. Mostpeoplehave46chromosomesinmostoftheircells: 23fromtheirmotherand23fromtheirfather. Eachchromosomeismadeupofgenes.Genescontaintheinformationyourbodyusestomakeproteins,thebodysbuildingblocks. Proteinsmakeupthestructureofyourorgansandtissues;theyarealsoneededforthebodyschemicalfunctionsandpathways. Eachproteinperformsaspecificjobinthebodysdifferenttypesofcells,andtheinformationformakingatleastoneproteiniscontainedinasinglegene.
ChecktheGlossaryonpages9 11 to
learnhow
to
saytheboldedwordsandwhat
theymean.
www.nichd.nih.gov
http:///reader/full/www.nichd.nih.govhttp:///reader/full/www.nichd.nih.gov -
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Thepatternorsequenceofyourgenesislikeablueprintthattellsyourbodyhowtobuilditsdifferentparts. Forexample,yourgenescontrolhowtallyouare,whatcoloryoureyesandhairare,andotherfeaturesofyourbodyandmind.Changes,ormutationsintheblueprintcanchangehowthebodyormindgrows/develops.Whatisautism?Autismisacomplexneurobiologicaldisorderofdevelopmentthatlaststhroughoutapersonslife.Itissometimescalledadevelopmentaldisabilitybecauseitusuallystartsbeforeagethree,inthedevelopmentalperiod,andbecauseitcausesdelaysorproblemsinmanydifferentskillsthatarisefrominfancytoadulthood.Themainsignsandsymptomsofautisminvolve1language,socialbehavior,andbehaviorsconcerningobjectsandroutines:Communicationbothverbal(spoken)and
non verbal (unspoken,suchaspointing,eyecontact,orsmiling)
Socialinteractionssuchassharingemotions,understandinghowothersthinkandfeel(sometimescalledempathy),andholdingaconversation,aswellastheamountoftimeapersonspendsinteractingwithothers
Routinesorrepetitivebehaviorsoftencalledstereotypedbehaviors,suchasrepeating
wordsoractionsoverandover,obsessivelyfollowingroutinesorschedules,playingwithtoysorobjectsinrepetitiveandsometimesinappropriateways,orhavingveryspecificandinflexiblewaysofarrangingitems
Peoplewithautismmighthaveproblemstalkingwithyou,ortheymightnotwanttolookyouintheeyewhenyoutalktothem. Theymayhavetolineuptheirpencilsbeforetheycanpayattention,ortheymaysaythesamesentenceagainandagaintocalmthemselvesdown. Theymayflaptheirarmstotellyoutheyarehappy,ortheymighthurtthemselvestotellyoutheyarenot. Somepeoplewithautismneverlearnhowtotalk.Thesebehaviorsnotonlymakelifedifficultforpeoplewhohaveautism,butalsotakeatollontheirfamilies,theirhealthcareproviders,theirteachers,andanyonewhocomesincontactwiththem.Becausedifferentpeoplewithautismcanhaveverydifferentfeaturesorsymptoms,healthcareprovidersthinkofautismasaspectrumdisorderagroupofdisorderswitharangeofsimilar
features.
Based
on
their
specific
strengths
andweaknesses,peoplewithautismspectrumdisorders(ASDs)mayhavemildsymptomsormoreserioussymptoms,buttheyallhaveanASD. ThisfactsheetusesthetermsASDandautismtomeanthesamething.Whatcausesautism?Scientistsdontknowexactlywhatcausesautism.Muchevidencesupportstheideathatgeneticfactorsthatis,genes,theirfunction,andtheirinteractionsareoneofthemainunderlyingcausesofASDs. But,researchersarentlookingforjustonegene. Currentevidencesuggeststhatasmanyas12ormoregenesondifferentchromosomesmaybeinvolvedinautismtodifferentdegrees.
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Somegenesmayplaceapersonatgreaterriskforautism,calledsusceptibility. Othergenesmaycausespecificsymptomsordeterminehowseverethosesymptomsare. Or,geneswithmutationsmightaddtothesymptomsofautismbecausethegenesorgeneproductsarent
workingproperly.Researchhasalsoshownthatenvironmentalfactors,suchasviruses,mayalsoplayaroleinautism.
Whilesomeresearchersareexamininggenesandenvironmentalfactors,otherresearchersarelookingatpossibleneurological,infectious,metabolic,andimmunologicfactorsthatmaybeinvolvedinautism.Becausethedisorderissocomplex,andbecausenotwopeoplewithautismareexactlyalike,autismisprobablytheresultofmanycauses.Whystudygenestolearnaboutautism?Pastresearchlinksautismandgenes. Forexample: StudiesoftwinswithautismScientistshave
studiedautisminbothidenticaltwinswhoaregeneticallythesameandfraternaltwinswhoaregeneticallysimilar,butnotthesame. Whenidenticaltwinshaveautism,bothhaveautismmorethan60percent1ofthetime,dependingonthecriteriaused.
Whenfraternaltwinshaveautism,bothhaveautismbetween0percent2and6percentofthetime. Ifgeneswerenotinvolvedinautism,therateofautismwouldbethesameforbothtypesoftwins.
FamilystudiesofautismStudiesoffamilyhistoriesshowthatthechancesabrotherorsisterofsomeonewhohasautismwillalsohaveautismisbetween2percentand8percent3,whichismuchhigherthaninthegeneralpopulation. Also,someoftheautism like symptoms,suchasdelaysinlanguagedevelopment,occurmoreoften4inparentsandadultbrothersandsistersofpeoplewithautismthaninfamilieswhohavenomembersorrelativeswithASDs. Becausemembersofthesamefamilyaremorelikelytosharegenes,somethingaboutthesegenessequencesappearstoberelatedtoautism.
DiagnosabledisordersandautismInabout5percent5ofautismcases,anothersingle gene disorder,chromosomedisorder,ordevelopmentaldisorderisalsopresent.Thistypeofco occurrence helpsresearchers
whoaretryingtopinpointthegenesinvolvedinautism. Similardisordersorconditions
withsimilarsymptomsmayhavesimilargeneticbeginnings. Incasesofonedisordercommonlyoccurringwithanother,itcouldbethatoneisactuallyariskfactorfortheother.Thiskindofinformationcanprovidecluesto
whatactuallyhappensinautism. Forexample,manypeoplewithASDsalsohaveepilepsy, aconditionmarkedbyseizures. Ifscientistscanunderstandwhathappensinepilepsy,theymayalsofindcluestowhathappensinautism.
Basedontheseandotherfindings,scientistshavelongfeltthattherewasalikelylinkbetweengenesandautism.
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But,howsymptomsofASDsaffectfamilymembersandthewidevarietyofsymptomsin
ASDstellresearchersthattheyarentlookingforjustonegene. So,evenwhenscientistsfindthegenesinvolvedinautism,theirworkwillbejustbeginning. Theywillstillhavetouncoverwhatrolesthegenesplayinthecondition.Howdoresearcherslookforthegenesinvolvedinautism?Scientistsgenerallyuseacombinationofmethodstofindcandidategenesgeneslikelytobeinvolvedinautism.
Screenthewholegenome.AgenomeisallthegeneticmaterialinapersonscellstheirDNA,theirgenes,andtheirchromosomes. Usually,researchersscreenthegenome
of
afamily
or
aset
of
families
that
has
morethanonememberwithanASD,tolookforcommonfeaturesanddifferences. Theylookforso called linksbetweenthosediagnosedwith
ASDsandthegeneswithinthesefamilies. Usingmarkerlocationsgeneswhosepositioninthegenomeisknownresearchers cannarrowdownthelocationofgenesinvolvedinASD. Ifageneinvolvedwithautismisclosetoaparticularmarker,scientistscanidentifythisgenebymappingitinrelationtotheknownmarkers.Conductcytogeneticstudies.Inacytogeneticstudy,researchersstainchromosomeswithadyeandthenlookatthemunderamicroscope. Thedyecreateslightanddarkbandsthatareuniquetoeachchromosome.Researcherscomparetheresultingbandsoftwo
peoplewithautism,ofonepersonwithautismandonerelative,orofonepersonwithautismandonepersonnotaffectedbyASD. Thesecomparisonscanpointoutsimilaritiesanddifferencesbetweenregionsonthechromosome,
whichresearcherscanthenstudyfurtherbasedonthetraitsofthatspecificregion.
Examinelinkageratios.Researchersusethisapproachtotofindhotspotsareasonchromosomesthatmaycontaingenesinvolvedinautism. Hotspotsarelikeneighborhoodsonthechromosome
wherethegenesinvolvedinautismmightreside. Inmanycases,genesinthesameareaofachromosomearetightlyconnectedtooneanother,andthisconnectionishardtobreak. Iftheconnectionispresentinmorepeoplethanyoumightexpectbychance,thesituationiscalledlinkagedisequilibrium.Linkagedisequilibriumhelpsresearchersnarrowtheirgeneticsearchtofindthespotinthechromosomalneighborhoodwherethegenemightbe.
Evaluategenesbasedontheirknownfunctions.Insomecases,researchersalreadyknowwhatthenormalfunctionofaspecificgeneorgenesis. Ifthatspecificfunctionisabnormalorincompleteinautism,researcherscanlookatthegenescontrollingthatfunctioninapersonwithautismtoseewhatisdifferentormissing. Or,theycanlookatwhatkindsofmedicationsareusefulincorrectingorcontrollingthatfunctiontoreducethesymptomsofautism. Theycanthenstudythechemicalpathwaysthatthesemedicationseffecttoseewhatstepmightbechangedor
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AUTISMANDGENES
missinginautism. Oncetheyvefoundthepathwayorthechange,theycanlookatthegenesthatcontrolthesefeaturesformoreinformationaboutautism. Thisapproachisknownasgeneticassociationanalysis.Whathaveresearchersfoundbystudyinggenesandautism?ResearchersintheCPEANetworkandtheircolleaguesaroundtheworldhavelearnedalotaboutautismthroughgeneticstudies,buttheystillhaveagreatdealtolearn. Todate,someoftheirfindingsincludethefollowing.
ChromosomeswhereimportantgenesarelikelytobefoundUsing genome wide screens, scientists have
identifiedanumberofgenesthatmightbeinvolvedinautism. Althoughsomeanalysessuggestthatasmanyas12genes6mightbeinvolvedinASDs,thestrongestevidence7,13pointstoareason: Chromosome2Scientistsknow7,10,11,12that
areasofchromosome2aretheneighborhoodsforhomeoboxorHOXgenes,thegroupofgenesthatcontrolgrowthanddevelopmentveryearlyinlife. Youhave38differentHOXgenesinyourchromosomalneighborhoods,andeachonedirectstheactionofothergenesinbuildingyourbodyandbodysystems.ExpressionoftheseHOXgenesiscriticaltobuildingthebrainstemandthecerebellum,twoareasofthebrainwherefunctionsaredisruptedinASDs.
Chromosome7Researchershavefound6,7,8,9averystronglinkbetweenthischromosomeandautism. TheirinvestigationsnowfocusonaregioncalledAUTS1,whichisverylikelyassociatedwithautism. MostofthegenomestudiescompletedtodatehavefoundthatAUTS1playssomeroleinautism. Thereisevidencethataregionofchromosome7isalsorelatedtospeechandlanguagedisorders.BecauseASDsaffectthesefunctions,autismmayinvolvethischromosome.
Chromosome13Inonestudy,35percent7,9offamiliestestedshowedlinkageforchromosome13. Researchersarenowtryingtoreplicatethesefindingswithotherpopulationsoffamiliesaffectedbyautism.
Chromosome15Genome wide screensandcytogeneticstudiesshowthatapartofthischromosomemayplayaroleinautism.Geneticerrorsonthischromosomecause
AngelmansyndromeandPrader Willi syndrome,bothofwhichsharebehavioralsymptomswithautism.Cytogeneticerrorsonchromosome15occur9inupto4percentofpatientswithautism.
Chromosome16Genesfoundonthischromosomecontrolawidevarietyoffunctions7that,ifdisrupted,causeproblemsthataresimilarorrelatedtosymptomsofautism. Forexample,ageneticerroronthischromosomecausestuberoussclerosis, adisorderthatsharesmanysymptomswithautism,includingseizures. So,regionsonthischromosomemayberesponsibleforcertainsimilarbehavioralaspectsofthetwodisorders.
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Chromosome 17A recent study found the
strongest evidence13 of linkage on this
chromosome among a set of more than 500
families whose male members were diagnosed
with autism. Missing or disrupted genes on
this chromosome can cause problems, such as
galactosemia, a metabolic disorder that, if left
untreated, can result in mental retardation.
Chromosome 17 also contains the gene for
the serotonin transporter, which allows nerve
cells to collect serotonin. Serotonin is
involved in emotions and helps nerve cellscommunicate. Problems with the serotonin
transporter can cause obsessive-compulsive
disorder (OCD), which is marked by
recurrent, unwanted thoughts (obsessions)
and/or repetitive behaviors (compulsions).
The X chromosomeTwo disorders that share
symptoms with autismFragile X syndrome
and Rett syndromeare typically caused by
genes on the X chromosome, which suggeststhat genes on the X chromosome may also play
a role in ASDs. People generally have 46
chromosomes in most of their cells23 from
their mother and 23 from their father. After
fertilization, the two sets match up to form 23
pairs of chromosomes. The chromosomes in
the 23rd pair are called the sex chromosomes,
X and Y. Their combination determines a
persons sexmales usually have one X and
one Y chromosome, and females usually havetwo X chromosomes. The fact that more
males than females have autism supports5,9 the
idea that the disorder involves genes on the X
chromosome. Females may be able to use their
other X chromosome to function normally,
while males, without such a back up show
symptoms of the condition.
Potential candidate genes
By focusing their studies on hot spots,
researchers have narrowed their search for
candidate genes. They need to do more work
to understand how many genes are involved,
and how these genes interact with each other
and with the environment to cause autism.
Researchers do have some promising leads
more leads than can be mentioned in this fact
sheet, but these are a few.
Researchers have found evidence that autism may
involve the HOXA1 gene. HOXA1, a homeobox
gene, plays a critical role in the development of
important brain structures, cranial nerves, the
ear, and the skeleton of the head and neck.
Researchers know that the HOXA1 gene is active
very early in lifebetween the 20th and 24th
days after conceptionand that any problem
with the genes function causes problems with the
development of these structures. Such problems
may contribute to the features of autism.
In one study10, nearly 40 percent of the persons
with autism carried a specific mutation in the
HOXA1 gene sequencenearly twice as many as
those who had the same change, but who did not
have autism and were not related to anyone with
autism. In addition, 33 percent of those who did
not have autism but were related to someone
with autism also had the mutation in their
HOXA1 gene. These findings mean that autismdoes not result from genetics alone, but that
some other factors are also involved in causing
the condition. If researchers can confirm an
association between this mutation and ASDs,
they may be able to detect the mutation as an
early test for autism, allowing important
interventions to start as early in life as possible.
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AUTISM AND GENES
Another study11 found that increased head size
in ASD patients was associated with a differentmutation in the HOXA1 gene. About 20 percent
of persons with autism have large head size. It is
one of the most consistently reported physical
features of persons with autism. Now researchers
want to know whether the mutation affects head
size in persons with autism only, or if it affects
head size in general, regardless of ASD status.
Several other genes have come forward as
potential candidates, including:
The Reelin (RELN) gene on chromosome 7
This gene plays a crucial role in the
development of connections between cells of
the nervous system. Researchers think that
abnormal brain connectivity plays a role in
autism, which makes Reelin a good candidate.
In addition, persons with autism and their
parents and siblings have lower levels of certain
types of the Reelin protein, which may meanthat gene is not functioning normally.
The HOXD1 geneThis homeobox gene is
critical to the formation of certain brain
structures. This gene is involved in Duane
syndrome, a disorder that causes eye-
movement problems and sometimes occurs
with autism. In one study12 of persons with
autism, nearly 94 percent of participants had
mutations in the same regions of HOXD1,which could mean that the region contributes
to ASDs.
Gamma-amino-butyric acid (GABA)
pathway genesGABA compounds are
neurotransmitters, which means they help
parts of the nervous system communicate with
each other. GABA receptor genes are involved
in early development of parts of the nervous
system and help with communication between
these parts throughout life. A problem in the
GABA pathway can cause some of the
symptoms of ASDs. For instance, epilepsy
may result, in part, from low levels of GABA
compounds. Many persons with autism alsohave epilepsy and also show low levels of
GABA. Current research focuses on genes
that, when their structure or function is
incorrect, cause autism-like problems in mice.
Serotonin transporter gene on chromosome 17
The serotonin transporter allows nerve
cells to collect serotonin so that they can
communicate. Serotonin is a neurotransmitter
involved in depression, alcoholism/problemdrinking, OCD, and other disorders. Research
shows that persons with autism have higher-
than-normal levels of serotoninranging
between 25 percent and 50 percent9,13 higher
than persons without autism. This higher
serotonin level may result from problems with
the serotonin transporter that arise from errors
in the gene.
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BodychemicalsthatmayplayaroleinautismThe body makes many chemicals that help it
functioncorrectly. Whenthesechemicalsaremissingorincorrect,thebodymayhaveproblemsfunctioningproperly,whichmayresultinsymptomsofautismorotherdisorders.Researchersarenowtryingtouncoverhowbodychemicalsmightbeinvolvedinautism,sotheycanlearnhowthegenesthatmakethesechemicalsmightalsoplayarole. Researchersarealsostudyingwhethermedicationsmightregulateorcontrolthesechemicalstocreatenormalchemicallevels. NormalizingthechemicalsinapersonwithASDsmightreducesymptoms.
Asmentionedearlier,GABAmayplayaroleinautismanddefinitelyplaysaroleinepilepsy.LevelsofdifferenttypesofGABAcompoundsareabnormallylowinpersonswithautism.Researchersbelievethattheselowlevelsmaycontributetoautism. Instudiesofmice,disruptingtheGABApathwaycausesseizures,extremereactionstotouchandsound,andstereotypedactionssymptomsalsocommoninautism. Researchnowfocusesonwhethermedicationsusedtotreattheseproblemscanalsoreducesomeofthesymptomsofautism.
Anotherbrainchemicalmentionedearlierserotoninisalsoout of balance inmanypersonswithautism. Highserotoninlevelsmayexplainwhypersonswithautismhaveproblemsshowingemotionandhandlingsensoryinformation,suchassounds,touch,andsmells.Researchersnowfocusonwhethermedicationsthatregulateserotoninlevelsmayimprovebehaviorinpersonswithautism. Theyalsoexaminethegenesthatmakeandregulateserotoninanditspathwaycomponentstoseeiftheycanfindanychangesorpatterns.
Whatdoesthefutureholdforstudiesofgenesandautism?ScientistsintheCPEANetworkandtheircolleagueswhostudythegeneticmechanismsofautismhopethatthesestudieswillrevealthemaincauseorcausesofautism. Doctorscouldthentestforthegeneorgenestodetectautismearlyinlifesothatinterventioncanbegin
whenitismosteffective. Or,researcherscoulddevelopdrugsthatchangeorregulatethegeneorgenestohelpnormalizebodychemicalsandbodyfunctions.Researcherssharetheirinformationandtheirmethodstoseeifotherresearcherscanreplicatetheirfindings. Havingseveralscientistsgetthesameresultsconfirmsthatdiscovery. Onceconfirmed,adiscoverybecomesthesteppingstonetootherdiscoveries. Todate,however,notallgeneticstudieshavegottenthesameresults.Therefore,additionalworkisstillimportant.Scientistsalsolookbeyondgenestofindfactorsthatmayplayaroleinautism,includingthingsintheenvironment. Environmentalfeaturescanaffecthowgenesfunction,whichmaycontributetothesymptomsofASDs. Byunderstandinggeneticandenvironmentalcausesofautism,scientistsmaybetterunderstandhowtotreatitandmaybeevenhowtopreventit. Doctorsandscientistscontinuetostudygenes,theenvironment,andgene environment interactionsuntiltheysolvethemysteriesofautism.
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GlossaryTheword Ispronounced AndmeansAngelmansyndrome Ayn JELL mann
sinn DROM AgeneticdisordercausedbyabnormalfunctionofthegeneUBE3A,locatedwithinasmallregiononchromosome15. Characteristicsinclude:developmentaldelay,lackofspeechorminimaluseofwords;movementorbalancedisorder,usuallyataxiaofgaitand/ortremulousmovementoflimbs,andanycombinationoffrequentlaughter/smiling;apparenthappydemeanor;easilyexcitablepersonality,oftenwithhandflappingmovements;hypermotoricbehavior;shortattentionspan.
Candidategene kan di DATE jeen
Agene,locatedinachromosomeregionsuspectedofbeinginvolvedinadisorder,whoseproteinproductsuggeststhatitcouldbethegeneinquestion.
Chromosome kro mu SOM Oneofthe"packages"ofgenesandotherDNAinthenucleusofacell.Humanshave23chromosomepairs,46inall.Eachparentcontributesonechromosometoeachpair,sochildrengethalfoftheirchromosomesfromtheirmothersandhalffromtheirfathers.
Cytogenetic sigh TOW jenn eh tik Studyofchromosomesusingaspecificmethodthatinvolvesstainingachromosomeandexaminingitunderamicroscope.
Duanesyndrome DWAYNEsinn DROM Aninheriteddisordercharacterizedbyinabilityofoneorbotheyestoturnoutwardbeyondthemidline. Insome
casesthereisalsoadeficitofinwardmotilityoftheeye(turningtowardthenose).
Epilepsy epp ih LEPP see Abraindisorderinwhichclustersofnervecells,orneurons,inthebrainsometimessignalabnormally.Inepilepsy,thenormalpatternofneuronalactivitybecomesdisturbed,causingstrangesensations,emotions,andbehaviororsometimesconvulsions,musclespasms,andlossofconsciousness.
FragileXsyndrome FRA jell EKSsinn DROM Themostcommonformofinheritedmentalretardation.Amutationinasinglegene,theFMR1geneontheX
chromosome,causesthedisorder,whichcanbepassedfromonegenerationtothenext.Symptomsoccurbecausethemutatedgenecannotproduceenoughofaproteinthatisneededbythebodyscells,especiallycellsinthebrain,todevelopandfunctionnormally.
Fraternaltwins frah TURN ul twinns Twinsresultingfromthefertilizationoftwoseparateeggs. Fraternaltwinsshareabout50percentoftheir
genes,justlikesiblingswhoarebornatdifferenttimes.Galactosemia guh lak toe SEE mee
uh Araredisorderinwhichthebodycannotprocessthesugargalactose,aby product ofmilkmetabolism.Buildupofgalactosepoisonsthebody,causingliver,kidney,andeyedamage,andevendeath(ifuntreated).
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Glossary(Continued)The word Is pronounced And meansGene jeen PiecesofDNA. Theycontaintheinformationfor
makingaspecificprotein.Genome JEE nom AlltheDNAcontainedinanorganismoracell;includes
boththeDNAandchromosomeswithinthenucleusandtheDNAoutsidethenucleus.
Hereditary ha RED ih tarry Ageneortraitpasseddownfromparenttooffspring.Homeoboxgenes HOE mee oh boks
jeenz Genesfoundinalmostallanimalsthatcontrolhowandwherepartsofthebodydevelop. Activeveryearlyinlife,actinglikeamoviedirectorbytellingothergeneswhentoactandwhentostopinbuildingthebody.
Hotspots hot spotz Areasonchromosomeswheremutations,activity,orrecombinationoccurswithunusuallyhighfrequency.
Identicaltwins eye DEN tik ul twinns Twinsformedfromthesplittingofthesamefertilizedegg,sotheyshare100percentoftheirgeneticmaterial.
Linkagedisequilibrium LINK aj DISS ee kwel ih bree
umAnassociationofgenesand/ormarkersneareachotheronachromosomethatismorethanwouldbeexpectedbychance.Linkedgenesandmarkerstendtobeinheritedtogether.
Mutation my TAH shun ApermanentstructuralchangeinDNA.Inmostcases,DNAchangeseitherhavenoeffectorcauseharm,butsomemutationsimproveanorganismssurvival.
Neurotransmitter
nyur OH tranz mitt er
Asubstance
that
transmits
nerve
impulses
between
nervecells.
Nucleus NOO klee us Thecentralcellstructurethathouseschromosomes.Obsessive
compulsivedisorder(OCD)
ahb SESS iv kum PUL shen DISS or dr
Adisordercharacterizedbyrecurrent,unwantedthoughts(obsessions)and/orrepetitivebehaviorsoranurgentneedtoperformrituals(compulsions).
Prader Willi syndrome PRAY derr WILL ee sinn DROM Anuncommoninheriteddisordercharacterizedbymentalretardation,decreasedmuscletone,short
stature,emotionalliability,andaninsatiableappetitethatcanleadtolife threatening obesity. Causedbyamissingpartonthepaternallyderivedchromosome15.
Protein
PRO teen
Alarge
molecule
made
up
of
one
or
more
chains
of
aminoacids.Proteinsperformawidevarietyofactivitiesinthecellandinthebody.
Replicate repp li KATE Describesasituationinwhichmanystudiesthatusethesamemethodsandstepshavegottenthesameoutcome,suggestingthatafindingislikelytobetrue.
Rettsyndrome RETTsinn DROM ResultsmostlyfrommutationsintheMECP2geneontheXchromosomeandoccursalmostexclusivelyin
girls.Afterseeminglynormaldevelopment,affectedgirlsdevelopproblemswithlanguage,learning,coordination,andotherbrainfunctions.
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Glossary(Continued)The word Is pronounced And meansSeizure SEE jyur Asuddenattack,oftenoneofconvulsions,asin
epilepsy. Seizuresdontnecessarilyinvolvemovementorthrashing;theycanalsomakesomeoneseemasthoughtheyarefrozen,unmoving.
Serotonin serr oh TOE ninn Aneurotransmitterthatisfoundespeciallyinthebrain,bloodserum,andstomachliningofmammals.
Stereotyped STARE ee oh tipd Anactionthatisrepeatedwithoutchange.Susceptibility suss ept ih BULL Thestateofbeingpredisposedto,sensitiveto,orof
lackingtheabilitytoresistmanifestationsofsomething(suchasapathogen,familialdisease,oradrug);apersonwhoissusceptibleismorelikelytoshowsymptomsofadisorder.
Tuberoussclerosis TOOB er us sklar OH siss Arare,multi system geneticdiseasethatcausesnon cancerous tumorstogrowinthebrainandon
othervitalorganssuchasthekidneys,heart,eyes,lungs,andskin.Itcommonlyaffectsthecentralnervoussystemandresultsinacombinationofsymptomsincludingseizures,developmentaldelay,behavioralproblems,skinabnormalities,andkidneydisease.
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9.Muhle,etal.(2004).TheGeneticsofAutism.Pediatrics,113(5):e472 e486.
10.IngramJL,StodgellCJ,HymanSL,FiglewiczDA,WeitkampLR,andRodierPM.(2000).DiscoveryofallelicvariantsofHOXA1andHOXB1: geneticsusceptibilitytoautismspectrumdisorders. Teratology,62:393 405.
11.Conciatori,etal.(2004).AssociationbetweentheHOXA1A218Gpolymorphismandincreasedheadcircumferenceinpatientswithautism. JournalofBiologicalPsychiatry,55:413 419.
12.Stodgell,etal.(2004).AssociationofHOXD1andGBX2allelicvariantswithautismspectrumdisorders.PresentedattheCPEA/STAARTAnnualScientificMeeting.
13.Cantor,etal.(2005).Replicationofautismlinkage:Finemappingpeakat17q21.AmericanJournalofHumanGenetics,76:1050 1056.
TheNICHDwouldliketothankFredVolkmar,M.D.,andEdCook,M.D.,fortheirassistanceonthisfactsheet.
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How can I get involved with studies of autism?
If you are interested in taking part in one of the CPEA studies, or if you want more information about
one of the CPEA sites, visit http://www.nichd.nih.gov/autism/cpea.cfm. You and your family are welcome
to take part in many different studies, but you can only take part in one genetics study at a time.
To find out what studies related to autism are currently looking for participants, go to
http://www.nichd.nih.gov/autism/research.cfm and choose the Autism clinical trials currently recruiting
patients link.
You can also visit http://www.clinicaltrials.govor call 1-800-411-1222 for more information on federally
funded studies that are seeking participants.
AUTISM RESEARCH AT THE NICHD
Where can I go for more information about genes and autism?
For more information about the CPEA Network, genetic studies, or autismresearch, contact the NICHD. The NICHD supports and conducts research ontopics related to the health of children, adults, families, and populations,including autism and developmental disabilities. The mission of the NICHD isto ensure that every person is born healthy and wanted, that women suffer no
harmful effects from the reproductive process, and that all children have thechance to fulfill their potential for a healthy and productive life, free of diseaseor disability, and to ensure the health, productivity, independence, and well-beingof all people through optimal rehabilitation. You can contact the NICHD throughthe NICHD Information Resource Centerat:
Mail: P.O. Box 3006, Rockville, MD 20847
Phone: 1-800-370-2943 (TTY: 1-888-320-6942)
Fax: 1-866-760-5947
E-mail: NICHDInformationResourceCenter@mail.nih.gov (Please use AUTISM in the subject line)
Internet: http://www.nichd.nih.gov/autism
The National Library of Medicine also provides information on ASDs athttp://www.nlm.nih.gov/medlineplus/autism.html. The NIH Web site also has informationabout ASDs at http://health.nih.gov/result.asp/62.
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NICHDNational Institute of Child Health& Human Development
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