A Brief Guide to Genomics

Genomics is the study of all of a person's genes (the genome), including interactions of those genes with each other and with the person's ... Skiptomaincontent ABriefGuidetoGenomics Genomicsisthestudyofallofaperson'sgenes(thegenome),includinginteractionsofthosegeneswitheachotherandwiththeperson'senvironment. WhatisDNA? Deoxyribonucleicacid(DNA)isthechemicalcompoundthatcontainstheinstructionsneededtodevelopanddirecttheactivitiesofnearlyalllivingorganisms.DNAmoleculesaremadeoftwotwisting,pairedstrands,oftenreferredtoasadoublehelix EachDNAstrandismadeoffourchemicalunits,callednucleotidebases,whichcomprisethegenetic"alphabet."Thebasesareadenine(A),thymine(T),guanine(G),andcytosine(C).Basesonoppositestrandspairspecifically:anAalwayspairswithaT;aCalwayspairswithaG.TheorderoftheAs,Ts,CsandGsdeterminesthemeaningoftheinformationencodedinthatpartoftheDNAmoleculejustastheorderoflettersdeterminesthemeaningofaword. WhatisDNA? Deoxyribonucleicacid(DNA)isthechemicalcompoundthatcontainstheinstructionsneededtodevelopanddirecttheactivitiesofnearlyalllivingorganisms.DNAmoleculesaremadeoftwotwisting,pairedstrands,oftenreferredtoasadoublehelix EachDNAstrandismadeoffourchemicalunits,callednucleotidebases,whichcomprisethegenetic"alphabet."Thebasesareadenine(A),thymine(T),guanine(G),andcytosine(C).Basesonoppositestrandspairspecifically:anAalwayspairswithaT;aCalwayspairswithaG.TheorderoftheAs,Ts,CsandGsdeterminesthemeaningoftheinformationencodedinthatpartoftheDNAmoleculejustastheorderoflettersdeterminesthemeaningofaword. Whatisagenome? Anorganism'scompletesetofDNAiscalleditsgenome.Virtuallyeverysinglecellinthebodycontainsacompletecopyoftheapproximately3billionDNAbasepairs,orletters,thatmakeupthehumangenome. Withitsfour-letterlanguage,DNAcontainstheinformationneededtobuildtheentirehumanbody.AgenetraditionallyreferstotheunitofDNAthatcarriestheinstructionsformakingaspecificproteinorsetofproteins.Eachoftheestimated20,000to25,000genesinthehumangenomecodesforanaverageofthreeproteins. Locatedon23pairsofchromosomespackedintothenucleusofahumancell,genesdirecttheproductionofproteinswiththeassistanceofenzymesandmessengermolecules.Specifically,anenzymecopiestheinformationinagene'sDNAintoamoleculecalledmessengerribonucleicacid(mRNA).ThemRNAtravelsoutofthenucleusandintothecell'scytoplasm,wherethemRNAisreadbyatinymolecularmachinecalledaribosome,andtheinformationisusedtolinktogethersmallmoleculescalledaminoacidsintherightordertoformaspecificprotein. Proteinsmakeupbodystructureslikeorgansandtissue,aswellascontrolchemicalreactionsandcarrysignalsbetweencells.Ifacell'sDNAismutated,anabnormalproteinmaybeproduced,whichcandisruptthebody'susualprocessesandleadtoadiseasesuchascancer.   Whatisagenome? Anorganism'scompletesetofDNAiscalleditsgenome.Virtuallyeverysinglecellinthebodycontainsacompletecopyoftheapproximately3billionDNAbasepairs,orletters,thatmakeupthehumangenome. Withitsfour-letterlanguage,DNAcontainstheinformationneededtobuildtheentirehumanbody.AgenetraditionallyreferstotheunitofDNAthatcarriestheinstructionsformakingaspecificproteinorsetofproteins.Eachoftheestimated20,000to25,000genesinthehumangenomecodesforanaverageofthreeproteins. Locatedon23pairsofchromosomespackedintothenucleusofahumancell,genesdirecttheproductionofproteinswiththeassistanceofenzymesandmessengermolecules.Specifically,anenzymecopiestheinformationinagene'sDNAintoamoleculecalledmessengerribonucleicacid(mRNA).ThemRNAtravelsoutofthenucleusandintothecell'scytoplasm,wherethemRNAisreadbyatinymolecularmachinecalledaribosome,andtheinformationisusedtolinktogethersmallmoleculescalledaminoacidsintherightordertoformaspecificprotein. Proteinsmakeupbodystructureslikeorgansandtissue,aswellascontrolchemicalreactionsandcarrysignalsbetweencells.Ifacell'sDNAismutated,anabnormalproteinmaybeproduced,whichcandisruptthebody'susualprocessesandleadtoadiseasesuchascancer.   WhatisDNAsequencing? SequencingsimplymeansdeterminingtheexactorderofthebasesinastrandofDNA.Becausebasesexistaspairs,andtheidentityofoneofthebasesinthepairdeterminestheothermemberofthepair,researchersdonothavetoreportbothbasesofthepair. Inthemostcommontypeofsequencingusedtoday,calledsequencingbysynthesis,DNApolymerase(theenzymeincellsthatsynthesizesDNA)isusedtogenerateanewstrandofDNAfromastrandofinterest.Inthesequencingreaction,theenzymeincorporatesintothenewDNAstrandindividualnucleotidesthathavebeenchemicallytaggedwithafluorescentlabel.Asthishappens,thenucleotideisexcitedbyalightsource,andafluorescentsignalisemittedanddetected.Thesignalisdifferentdependingonwhichofthefournucleotideswasincorporated.Thismethodcangenerate'reads'of125nucleotidesinarowandbillionsofreadsatatime. ToassemblethesequenceofallthebasesinalargepieceofDNAsuchasagene,researchersneedtoreadthesequenceofoverlappingsegments.Thisallowsthelongersequencetobeassembledfromshorterpieces,somewhatlikeputtingtogetheralinearjigsawpuzzle.Inthisprocess,eachbasehastobereadnotjustonce,butatleastseveraltimesintheoverlappingsegmentstoensureaccuracy. ResearcherscanuseDNAsequencingtosearchforgeneticvariationsand/ormutationsthatmayplayaroleinthedevelopmentorprogressionofadisease.Thedisease-causingchangemaybeassmallasthesubstitution,deletion,oradditionofasinglebasepairoraslargeasadeletionofthousandsofbases. WhatisDNAsequencing? SequencingsimplymeansdeterminingtheexactorderofthebasesinastrandofDNA.Becausebasesexistaspairs,andtheidentityofoneofthebasesinthepairdeterminestheothermemberofthepair,researchersdonothavetoreportbothbasesofthepair. Inthemostcommontypeofsequencingusedtoday,calledsequencingbysynthesis,DNApolymerase(theenzymeincellsthatsynthesizesDNA)isusedtogenerateanewstrandofDNAfromastrandofinterest.Inthesequencingreaction,theenzymeincorporatesintothenewDNAstrandindividualnucleotidesthathavebeenchemicallytaggedwithafluorescentlabel.Asthishappens,thenucleotideisexcitedbyalightsource,andafluorescentsignalisemittedanddetected.Thesignalisdifferentdependingonwhichofthefournucleotideswasincorporated.Thismethodcangenerate'reads'of125nucleotidesinarowandbillionsofreadsatatime. ToassemblethesequenceofallthebasesinalargepieceofDNAsuchasagene,researchersneedtoreadthesequenceofoverlappingsegments.Thisallowsthelongersequencetobeassembledfromshorterpieces,somewhatlikeputtingtogetheralinearjigsawpuzzle.Inthisprocess,eachbasehastobereadnotjustonce,butatleastseveraltimesintheoverlappingsegmentstoensureaccuracy. ResearcherscanuseDNAsequencingtosearchforgeneticvariationsand/ormutationsthatmayplayaroleinthedevelopmentorprogressionofadisease.Thedisease-causingchangemaybeassmallasthesubstitution,deletion,oradditionofasinglebasepairoraslargeasadeletionofthousandsofbases. WhatistheHumanGenomeProject? TheHumanGenomeProject,whichwasledattheNationalInstitutesofHealth(NIH)bytheNationalHumanGenomeResearchInstitute,producedaveryhigh-qualityversionofthehumangenomesequencethatisfreelyavailableinpublicdatabases.ThatinternationalprojectwassuccessfullycompletedinApril2003,underbudgetandmorethantwoyearsaheadofschedule. Thesequenceisnotthatofoneperson,butisacompositederivedfromseveralindividuals.Therefore,itisa"representative"orgenericsequence.ToensureanonymityoftheDNAdonors,morebloodsamples(nearly100)werecollectedfromvolunteersthanwereused,andnonameswereattachedtothesamplesthatwereanalyzed.Thus,noteventhedonorsknewwhethertheirsampleswereactuallyused. TheHumanGenomeProjectwasdesignedtogeneratearesourcethatcouldbeusedforabroadrangeofbiomedicalstudies.Onesuchuseistolookforthegeneticvariationsthatincreaseriskofspecificdiseases,suchascancer,ortolookforthetypeofgeneticmutationsfrequentlyseenincancerouscells.Moreresearchcanthenbedonetofullyunderstandhowthegenomefunctionsandtodiscoverthegeneticbasisforhealthanddisease. WhatistheHumanGenomeProject? TheHumanGenomeProject,whichwasledattheNationalInstitutesofHealth(NIH)bytheNationalHumanGenomeResearchInstitute,producedaveryhigh-qualityversionofthehumangenomesequencethatisfreelyavailableinpublicdatabases.ThatinternationalprojectwassuccessfullycompletedinApril2003,underbudgetandmorethantwoyearsaheadofschedule. Thesequenceisnotthatofoneperson,butisacompositederivedfromseveralindividuals.Therefore,itisa"representative"orgenericsequence.ToensureanonymityoftheDNAdonors,morebloodsamples(nearly100)werecollectedfromvolunteersthanwereused,andnonameswereattachedtothesamplesthatwereanalyzed.Thus,noteventhedonorsknewwhethertheirsampleswereactuallyused. TheHumanGenomeProjectwasdesignedtogeneratearesourcethatcouldbeusedforabroadrangeofbiomedicalstudies.Onesuchuseistolookforthegeneticvariationsthatincreaseriskofspecificdiseases,suchascancer,ortolookforthetypeofgeneticmutationsfrequentlyseenincancerouscells.Moreresearchcanthenbedonetofullyunderstandhowthegenomefunctionsandtodiscoverthegeneticbasisforhealthanddisease. Whataretheimplicationsformedicalscience? Virtuallyeveryhumanailmenthassomebasisinourgenes.Untilrecently,doctorswereabletotakethestudyofgenes,orgenetics,intoconsiderationonlyincasesofbirthdefectsandalimitedsetofotherdiseases.Thesewereconditions,suchassicklecellanemia,whichhaveverysimple,predictableinheritancepatternsbecauseeachiscausedbyachangeinasinglegene. WiththevasttroveofdataabouthumanDNAgeneratedbytheHumanGenomeProjectandothergenomicresearch,scientistsandclinicianshavemorepowerfultoolstostudytherolethatmultiplegeneticfactorsactingtogetherandwiththeenvironmentplayinmuchmorecomplexdiseases.Thesediseases,suchascancer,diabetes,andcardiovasculardiseaseconstitutethemajorityofhealthproblemsintheUnitedStates.Genome-basedresearchisalreadyenablingmedicalresearcherstodevelopimproveddiagnostics,moreeffectivetherapeuticstrategies,evidence-basedapproachesfordemonstratingclinicalefficacy,andbetterdecision-makingtoolsforpatientsandproviders.Ultimately,itappearsinevitablethattreatmentswillbetailoredtoapatient'sparticulargenomicmakeup.Thus,theroleofgeneticsinhealthcareisstartingtochangeprofoundlyandthefirstexamplesoftheeraofgenomicmedicineareuponus. Itisimportanttorealize,however,thatitoftentakesconsiderabletime,effort,andfundingtomovediscoveriesfromthescientificlaboratoryintothemedicalclinic.Mostnewdrugsbasedongenome-basedresearchareestimatedtobeatleast10to15yearsaway,thoughrecentgenome-driveneffortsinlipid-loweringtherapyhaveconsiderablyshortenedthatinterval.Accordingtobiotechnologyexperts,itusuallytakesmorethanadecadeforacompanytoconductthekindsofclinicalstudiesneededtoreceiveapprovalfromtheFoodandDrugAdministration. Screeninganddiagnostictests,however,arehere.Rapidprogressisalsobeingmadeintheemergingfieldofpharmacogenomics,whichinvolvesusinginformationaboutapatient'sgeneticmake-uptobettertailordrugtherapytotheirindividualneeds. Clearly,geneticsremainsjustoneofseveralfactorsthatcontributetopeople'sriskofdevelopingmostcommondiseases.Diet,lifestyle,andenvironmentalexposuresalsocomeintoplayformanyconditions,includingmanytypesofcancer.Still,adeeperunderstandingofgeneticswillshedlightonmorethanjusthereditaryrisksbyrevealingthebasiccomponentsofcellsand,ultimately,explaininghowallthevariouselementsworktogethertoaffectthehumanbodyinbothhealthanddisease. Whataretheimplicationsformedicalscience? Virtuallyeveryhumanailmenthassomebasisinourgenes.Untilrecently,doctorswereabletotakethestudyofgenes,orgenetics,intoconsiderationonlyincasesofbirthdefectsandalimitedsetofotherdiseases.Thesewereconditions,suchassicklecellanemia,whichhaveverysimple,predictableinheritancepatternsbecauseeachiscausedbyachangeinasinglegene. WiththevasttroveofdataabouthumanDNAgeneratedbytheHumanGenomeProjectandothergenomicresearch,scientistsandclinicianshavemorepowerfultoolstostudytherolethatmultiplegeneticfactorsactingtogetherandwiththeenvironmentplayinmuchmorecomplexdiseases.Thesediseases,suchascancer,diabetes,andcardiovasculardiseaseconstitutethemajorityofhealthproblemsintheUnitedStates.Genome-basedresearchisalreadyenablingmedicalresearcherstodevelopimproveddiagnostics,moreeffectivetherapeuticstrategies,evidence-basedapproachesfordemonstratingclinicalefficacy,andbetterdecision-makingtoolsforpatientsandproviders.Ultimately,itappearsinevitablethattreatmentswillbetailoredtoapatient'sparticulargenomicmakeup.Thus,theroleofgeneticsinhealthcareisstartingtochangeprofoundlyandthefirstexamplesoftheeraofgenomicmedicineareuponus. Itisimportanttorealize,however,thatitoftentakesconsiderabletime,effort,andfundingtomovediscoveriesfromthescientificlaboratoryintothemedicalclinic.Mostnewdrugsbasedongenome-basedresearchareestimatedtobeatleast10to15yearsaway,thoughrecentgenome-driveneffortsinlipid-loweringtherapyhaveconsiderablyshortenedthatinterval.Accordingtobiotechnologyexperts,itusuallytakesmorethanadecadeforacompanytoconductthekindsofclinicalstudiesneededtoreceiveapprovalfromtheFoodandDrugAdministration. Screeninganddiagnostictests,however,arehere.Rapidprogressisalsobeingmadeintheemergingfieldofpharmacogenomics,whichinvolvesusinginformationaboutapatient'sgeneticmake-uptobettertailordrugtherapytotheirindividualneeds. Clearly,geneticsremainsjustoneofseveralfactorsthatcontributetopeople'sriskofdevelopingmostcommondiseases.Diet,lifestyle,andenvironmentalexposuresalsocomeintoplayformanyconditions,includingmanytypesofcancer.Still,adeeperunderstandingofgeneticswillshedlightonmorethanjusthereditaryrisksbyrevealingthebasiccomponentsofcellsand,ultimately,explaininghowallthevariouselementsworktogethertoaffectthehumanbodyinbothhealthanddisease. RelatedContents AboutGenomics WhatistheHumanGenomeProject? FactSheets DeoxyribonucleicAcid(DNA)FactSheet AboutGenomics HumanGenomeProjectFAQ CurrentSlide CurrentSlide CurrentSlide AboutGenomics WhatistheHumanGenomeProject? FactSheets DeoxyribonucleicAcid(DNA)FactSheet AboutGenomics HumanGenomeProjectFAQ CurrentSlide CurrentSlide AboutGenomics WhatistheHumanGenomeProject? FactSheets DeoxyribonucleicAcid(DNA)FactSheet AboutGenomics HumanGenomeProjectFAQ Lastupdated:August15,2020