Functional and structural characterization of missense mutations in PAX6 gene.pdfVIP

Front．Bio1．2015，10(4)：377—385 D0I10．1007／sl1515．O15．1346．2 FunctionaIandstructuraICharaCteriZati0nofmissense mutationsinPAX6gene s．UdhayaKumar,N．Priyanka，RSneha，C．GeorgePriyaDoss(圜) MedicalBiotechnologyDivision，SchoolofBiosciencesandTechnology,VITUniversity,Vellore,TamilNadu632014,India ◎ HigherEducationPressandSpringer-VerlagBerlinHeidelberg2015 Abstract The genebelongstothePairedbox(PAX)familyoftranscriptionfactorsthatistissuespecificand required forthedifferentiation and proliferation ofcellsin embryonicdevelopment．PAX6regulatesthepartern ofrmation in early developmentalstages．This function ofPAX6 protein enablesthe successfulcompletion of neurogenesisandoculogenesisinmostanimalssuchasmice，Drosophilaandsomeothermodelorganismsincluding humans．Avariationinthesequenceof genemayalterthefunctionandstructureofthept-otein．Suchchangescan produceadverseeffectsonfunctioningofthePAX6|proteinwhichwereclinicallyobservedtoOccurinabroadrangeof oculardefectssuchasaniridiainhumans．W eemployed ／nsilicopredictionmethodssuchasSIFT．PolyPhen2：Imutant 3．O，SNAE SNPs＆GO，andPHD．SNPtoscreenthepathogenicmissensemutationinPAX6andDNAbindingsitesby BindN andBindN+ ．Furthermore．weemployedl(D4V servertoexaminethestructuralandfunctionalmodifications thatoccur in thePAX6proteinasaresultofmutation．BasedontheresnItsobtainedfrom the ／n silicoprediction methods，wecarriedoutmodelinganalysisofrV53L，I56 G64V,andI87R tovisualizetheimpactofmutationin structuralcontext． Keywords PAX6，missensemutation，DNA—protein Introduction aniridia(Hil1eta1．，1991；Matsuoeta1．，1993：Osumieta1．， 1997；Mishraeta1．．2002)．whichisarareoculardisorder isamemberofvertebratepairedboxfamilyofgenes． whichcausesincompleteformationoftheiris．Aniridiahasa Paired box genes are tissue．specific transcription factors globalprevalenceof1in64000to1in96000．4 genehas whichplayasignificantrole