FUS、TARDBP基因在中國肌萎縮側(cè)索硬化人群中的突變研究.pdf

1、北京協(xié)和醫(yī)學(xué)院(中國醫(yī)學(xué)科學(xué)院)碩士學(xué)位論文FUS、TARDBP基因在中國肌萎縮側(cè)索硬化人群中的突變研究姓名：彭郁申請學(xué)位級別：碩士專業(yè)：臨床醫(yī)學(xué)專業(yè)指導(dǎo)教師：崔麗英201106FUSandTARDBPMutationsinAmyotrophieLateralSclerosisCasesfromChinaABSTRACTAmyotrophielateralsclerosis(ALS)isafatalneurodegenerativedi

2、seasecharacterizedbyprogressivemuscularparalysisreflectingdegenerationofmotorneurol岱intheprimarymotorcortex，corticospinaltracts，brainstemandspinalcordALSisakindofcomplexdiseasecontributedbymultiplegeneticandenvironmental

3、factorsTenpercentofCaseshaveafamilialhistoryUbiquitinatedproteinaggregatesinthecytoplasmisthehallmarkofALSasmanyotherneurodegenerativediseaseRecentresearcheshaveshowedthatthemaincomponentoftheseabnormalinclusionsaretrans

4、activeresponseDNAbindingprotein(TARDBP)andfusedinsarcomaprotein(FUS)ManymutationsofthesetwogeneshavebeenreportedThestructuralandfunctionalsimilaritiesofTfU①BPandFUS，whichalebomDNA／RNAbindingproteins，suggestthatabnormalRN

5、AmetabolismmaybeoneofthepathogenicmechanismsofALSOBJECTIVE：TodeterminethefrequencyofFUSand!llARDBPmutationsinacohortofALSCasesfromChinaMETHODS：Werecruited7familialALS(FALS)families，137sporadicALS(SALS)easesand90matchedco

6、ntrolsforourstudyGenomicDNAWasextractedformwholebloodsamples111ecodingregionofFUSexon14，15andTARDBPexon6wereamplifiedbypolymerasechainreaction(PCR)mPCRproductsweresequencedbycompany’RESUIJTS：1Wbobserved3singlenucleotidec

7、hangesinFUSandallofthemwereheterozygousAmissensemutationQAr9521LeucG1562T)wasobservedinaFALS。Asynonymousmutation(cC1464T)WasobservedinaSALScalseThethirdmutationcC1595TwhichWasbehindthestopcodonwasobservedinaSALScaseThese

8、nucleotidechangeswerenotobservedinthecontrols2TheTARDBPexon6of65SALSCaSesinthe137weresequencedbyDrLinpreviouslyAmongtheothersweobservedoneheterozygousmissensemutationQGly348ViIl，cO1043T)inaSALScase11lismutationWasnotobse

9、rvedinthecontrolsCONCLUSIONS：1MutationsinFUSaccountfor143％(1of7)ofFALSandO％ofSALSinourChinesecohortThefrequencyofFUSmutationinOUrChineseFALSisequaltothatreportedinAsiacohorts，andthefrequencyofAsiacohortsisobviouslyhigher