216582155

Evaluating the Role of Non-coding Nucleotide Repeat Expansions in Amyotrophic Lateral Sclerosis

Katherine Carr, Anna Thomas, Matthew Figley, Aaron Gitler

Department of Genetics, Stanford University School of Medicine

ABSTRACT    U MATERIALS & METHODS

•    ArryccroęfK leearal sOerous (AIS) tt a

rtAftbry -vs<a mo%t"a* The a .e*n;e    tipeotancy of a

pa*«r< *n ał$ *s r»o to fv* >tar* «“.«< o*jro*s The causa* of ALS aro poorty tftoerstood So-ra

repeat e>parvsora occur*tg r (he coorg regon of

ciotom ha.* oaa« n*«d to ais w ir<m    cojo

afco Ca io«W r»    regon Eipmw* r mm

repeat* ara **toc*!ed we cn*r r*u*ooegeneraeYe cm a rota for (hem * AIS a <s+r<r*r\

•    We pe^xrred cor^»M chart reeclon (PCR) r«3 trapT** ansT)Vi » ascenan * nera •« a ofrerence n receawaaMMacigKiw wa assestao M ergn* of eeacn 6 and au*n tO n 364 cortro* and 366 AL$ paeerts _

HYPOTHESIS

waf^poMwefl w rwacwf rwa* eiwcm « oc*v coorg regon* mgN ca etwcaiw »Ch Ai$ To tost n*s h>po<nes«s *a OefneO (ha rodecftde repeat lergn ofteo pe<a* n a largeruntercfALScases and heairy contro*

BACKGROUND

•Al$ęrmar#y affects peopto 0««aeen na egwcfłOanflM •*» 6-10% of cam lama* rto »-tt% of cases sporaoa Rflu*oto «i na orfy *DA apęro.ed ong tor ais ano « tajen gwanef a ransporfer*

• Arece* 0My oetormrao that rtermeaete-tongn PW-amra repeat a apansons n w«n 2areesłOcaM ■*» ocrMM4 r*x tor AIS '² Rcfygtotamra repeat ara encodcopyrectsofneowctocwe CAG

• NcrKCOnj repeat emanom r na geoe C90RF72 aara -5ert^3 to causa 23% of famfcai AIS cases *

M"vmim a*»M a*»y

hAS. tacowa %e*a»e w    na -vk%* mwma

V-

DNA Amplification & Analysis

	,1,1
W®	ewTypci to

NapCorc

Facilily

Jk

(M Mł „I

RESULTS

OMM

W je^ryt* rd Arta- cT wKf^oi coJd Ca i^redfv» na racntcfra^oy* łam «k«a e satogran >it r*j* to v^o- na aanoueao efMhaaaeet ofta r»pM!ea*mc«n nAL$*«d

Ar«ne<iea(iiett*MMedioM«(MwafNe>»anon •a^ fttecacaaey    >teaa<rca

' •> Fragment Analysis Via Capillary Gol Electrophoresis

ctoctrophyeus emptoy* ra pr«pt o* «cfow<« foa Fragmercs mgrato Cy wa vp na capAaras ałh larger '    rwng Uo*a< FkorM<«ay laOetoO fregnertt ara

oaoectao ara rte^KM Mag Gera uacper softoare m ę*a*s ara gener «6ed

a we standard isosadtocreaeaacwaahj nahn/raresaranea cpTpa-c-j to (ha c**ve Accur#ęy n «aha era oasa par offaraoce

k___/

F***# 7. Wł*NV#y AUun •

<]<■ • s a iwm	-
	—
«a<	1	1 »|
JM
•M

»a wa ma jw* ma« Mir

2: The *»«**    e*«e<<a*y v*o*e «* NOPTItt. **+/ aa

see* et ra ae<i^ea»M im# a*V# KC^TOO) f*ae**e» *y v*r^ toays* wmłh epaesaa* *e to S**p«' ie^tr<e aa to va*fy ra W.e*r» WH artpra

3 Auut 10 tottofram e#e»ci*Q Pa repeat

Ttpwre y- 6©r AA.S rd cera* toto- eNęhe*    The

Oftorencee-ere not lartAceNtotedcrtereMfieuctMit

V*___/

CONCLUSION

• to preameary rewh ahereas ra rwrter and wa P* repeat imamom »a»smier torataxn •.OOetween cases and ccnWł. toraUui S»a ottoraatf aposstto ocreasedrar©a< pfreęeac

emimom

-    Nuetootta rapaac imrwm nau«rt i0erau*MV toccrtrPufe to AIS Aiaui 6 4 a cM«3toa kr^thn^ oaooo<** COhOrtSOfAlS CłMłtojcorCroa

-    We ar* now rr/ettgeeng totoorta raptotamamom neo«v cotog gioet and rtHyrrę mora patero* tor euin $ Ox Utoet •mtoJ na poccrtef roto of nudecooe rece««mamom asa pdertaJ porcgerK maoharbsm n ALS

REFERENCES

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*MA*t«*73to> »0a*-t0?1 itotoł

2    kee t « m (aaimMt«Tar<«c>pt»łr«rr«*we»er>»< » •V5**5to« ar«Kr»*

3    D>.<m wrow U «• (ęrOMG4O0CCaa\<«9m«ipMir So><o»a«to«ycrcaoaar:CMtC^y»<-ya tocraec»TOeaAcł

3*S^M(20U3

4    '«« a •>« isuiMMeNArMs^ra^rRaNiier^PMrgri A^iy.w^of, IM, at-JOCum

ACKNOWLEDGEMENTS

Apcrecatco is grreo to na Stanford tosiAAes cfMedcrte Suw Research iSłMR) ara to rramtars of ra Cerata tosaojoa. sęac^aaey na G«ar LaO for aoaoirg hł prp^ct Reoognoon is ano tattoaed wpon /ceuroa Oav Mana Armanoto Ssephana Zmmerman Catoy Urp James Evans. and JafTrnyWaoe