分子医学-表观遗传学.ppt

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分子医学-表观遗传学.ppt

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Epigenetics

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TheHumanGenomeProject(HGP)Keyfindings:approx.24,000genesinhumanbeingallhumanracesare99.99%alikeChallenges:about24,000genesvs.100,000proteinsnon-coding(98%)vs.codingDNA(2%)genotypevs.phenotypeIntroductiontoEpigenetics

Theymaylookthesame,butarethey?Position-effectvariegationParamutationatthemaizeEpigeneticbiologyIntroductiontoEpigenetics

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EpigeneticsDefinition:Thestudyofanypotentiallystableand,ideally,heritablechangeingeneexpressionorcellularphenotypethatoccurswithoutchangesinWatson-Crickbase-pairingofDNA.Oneexample:cellulardifferentiation/developmenttotipotentstemcellsbecomethevariouspluripotentcelllinesoftheembryowhichinturnbecomefullydifferentiatedcellsIntroductiontoEpigenetics

Change:Geneticsvs.EpigeneticsIntroductiontoEpigenetics

1938,HermannMullerfirstdescribedthePosition-effectvariegation1942,ConradWaddingtondefinedepigeneticsas“thebranchofbiologywhichstudiesthecausalinteractionsbetweengenesandtheirproducts,whichbringthephenotypeintobeing”1950s,R.BrinkdiscoveredParamutationinmaize1961,MaryLyonproposedtherandominactivationofonefemaleXchromosometoexplainthemottledphenotypeoffemalemiceheterozygousforcoatcolorgenes1983,discoveredtheDNAmethylation……BriefHistoryofEpigeneticsIntroductiontoEpigenetics

EpigeneticsEventsparamutationbookmarkingimprintinggenesilencingXchromosomeinactivationpositioneffectreprogrammingtransvectionmaternaleffectsIntroductiontoEpigenetics

EpigeneticResearch:techniquesChIP;ChIP-on-chip;ChIP-seqfluorescentinsituhybridizationmethylation-sensitiverestrictionenzymes HpaII(CCGG)andMspI(CCGG)DNAadeninemethyltransferaseidentification(DamID)