Module2DNA-theSecretofLifePartTwo:TeachingResources第二部分教学资源Section2:Backgroundinformation1.HowisDNAsequencingdone?DNAsequencing,theprocessofdeterminingtheexactorderofthe3billionchemicalbuildingblocks(calledbasesandabbreviatedA,T,C,andG)makinguptheDNAofthe24differenthumanchromosomes,isthegreatesttechnicalchallengeintheHumanGenomeProject.Achievingthisgoalwillhelprevealtheestimated100,000humangeneswithinourDNAaswellastheregionscontrollingthem.TheresultingDNAsequencemapswillbeusedby21stcenturyscientiststoexplorehumanbiologyandothercomplexphenomena.MeetingHumanGenomeProjectsequencinggoalsby2003willrequirecontinualimprovementsinsequencingspeed,reliability,andcosts.StandardmethodsarebasedonseparatingDNAfragmentsbygelelectrophoresis,whichisextremelylaborintensiveandexpensive.Totalsequencingoutputinthecommunitywasabout200Mbfor1998.Encouragingprogressrangesfromenhancementsofgel-basedtechnologiesandthedevelopmentofnovel,gel-lessautomatableapproaches,suchastheuseofDNAfragmentsboundtoasolidsurfaceDNAchips,andseparationoffragmentsbymassspectrometry.Newgel-basedsequencersusemultipletiny(capillary)tubestorunstandardelectrophoreticseparations.Theseseparationsaremuchfasterbecausethetubesdissipateheatwellandallowtheuseofmuchhigherelectricfields.Seeafiguredepictingthistechnology.2.Whatisthedifferencebetweendraftsequenceandfinishedsequence?Anewgoal(5/99)oftheHGPistogenerateascaffoldofknownDNAsequenceacrossanestimated90%ofthehumangenome.This"workingdraft"sequencewillbeofloweraccuracythanthefinishedsequenceandwillnotbecontinuousacrossthe3billionbasesofthehumangenome.However,thedatawillbeinvaluabletomanybiomedicalscientistsastheystrivetounderstandgenesimportanttotheirownresearch.用心爱心专心116号编辑GeneratingthedraftwillrequireresearcherstosequenceeachpieceofDNAonlyabout5times,insteadoftheusual10timesusedforobtainingthehighestqualitysequencethatis99.99%completeandallowsforonlyasingleerrorin10,000bases.RemaininggapsanderrorsintheworkingdraftsequencewillbecorrectedovertheyearstoachievetheultimategoaloftheHumanGenomeproject:acomplete,high-qualityhumanDNAreferencesequenceby2003.3.ThenormalcellcycleInmosttissuesofthebody,cellsmultiplythroughaprocessknownasthecellcycle.Beforecellscanmultiplyanddivideintoothercells,theyhavetomakeexactcopiesoftheirDNA.DNAisthegeneticcodethatisinallthecellsofourbodiesandisexactlythesamecodeineachcellnomatterwhattissuethecellisfrom.ChromosomesaremadeupofthegenesofourcellsandourgenesaremadeupofstrandsofDNA.Eachcellofourbodyhastwocopiesofeachgene,oneinheritedfromourmotherandonefromourfather.Thenucleusofthecellhousesourchromosomesandgenes.Normally,mostcellsarenotactivelygrowinganddividingandareintheG0orrestingphaseofthecellcycleandhaveadiploidor2NDNAcontent.CellsintheG1phaseareactivelycyclingbutlikeG0cellshavea"diploid"or2NDNAcontent.AsmallpercentageofcellsinnormaltissuesareundergoingDNAsynthesis(makingacopyoftheirDNA)andareintheSphaseofthecellcycle(haveaDNAcontentbetween2Nand4N).AfewcellshavecompletedtheirDNAsynthesisanddoubledtheiramountofDNAandareintheG2phaseofthecellcycle(havea4NortetraploidDNAcontent).AftercellsdoubletheirDNA,theyundergomitosis(Mphase)dividingintotwodaughtercellsthatareexactgeneticcopiesofeachotherandhaveaDNAcontentof2N.Nowell'shypothesisTherearemanyeventsorstepsthatoccurinBarrett'sesophagusthatleadtothedevelopmentofcancer.Afewoftheseeventsar...
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