Age and Haplotype Variations within FADS1 Interact and Associate with Alterations in Fatty Acid Composition in Human Male Cortical Brain Tissue 英文参考文献.docVIP

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Age and Haplotype Variations within FADS1 Interact and Associate with Alterations in Fatty Acid Composition in Human Male Cortical Brain Tissue 英文参考文献.doc

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Age and Haplotype Variations within FADS1 Interact and Associate with Alterations in Fatty Acid Composition in Human Male Cortical Brain Tissue 英文参考文献

AgeandHaplotypeVariationswithinFADS1Interactand AssociatewithAlterationsinFattyAcidCompositionin HumanMaleCorticalBrainTissue ErikaFreemantle1,3,AleksandraLalovic3,NaguibMechawar2,3,GustavoTurecki1,2,3 * 1Department of Genetics, McGill University, Montreal, Quebec, Canada, 2Department of Psychiatry, McGill University, Montreal, Quebec, Canada, 3McGill Group for SuicideStudies,DouglasMentalHealthUniversityInstitute,Montreal,Quebec,Canada Abstract Fatty acids (FA) play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1/2/3)geneclusterasanimportantcontributortoFAalterationsinserumlipidsaswellasmeasuresofFAdesaturase indexestimatedbyratiosofrelevantFAs.ThecontributiontoalterationsofFAswithinthebrainbylocalsynthesisisstilla matterofdebate.Thus,theimpactofgeneticvariantsinFADSgenesongeneexpressionandbrainFAlevelsisanimportant avenuetoinvestigate. Methods:AnalyseswereperformedonbraintissuefromprefrontalcortexBrodmannarea47(BA47)of61malesubjectsof FrenchCanadianancestryranginginagefromyoungadulthoodtomiddleage(18–58yearsold),withtheexceptionofone teenager(15yearsold).HaplotypetaggingSNPswereselectedusingthepubliclyavailableHapMapgenotypingdatasetin conjunctionwithHaploview.DNAsequencingwasperformedbytheSangermethodandgeneexpressionwasmeasuredby quantitativereal-timePCR.FAsinbraintissuewereanalysedbygaschromatography.VariantsintheFADS1generegion weresequencedandanalyzedfortheirinfluenceonbothFADSgeneexpressionandFAsinbraintissue. Results:Ourresultssuggestanassociationoftheminorhaplotypewithalterationinestimatedfattyaciddesaturaseactivity. AnalysisoftheimpactofDNAvariantsonexpressionandalternativetranscriptsofFADS1andFADS2,however,showedno differences.Furthermore,therewasasignificantinteractionbetweenhaplotypeandageoncertainbrainFAlevels. Discussion: This study suggests that genetic variability in the FA