Human genome project and elsi

Human genome project, milestones and ELSI of HGP

1. Human Genome
Project
Dr. N. Yuvaraj
Assistant Professor
AchariyaArts and Science College
Villianur, Puducherry

2. TheHumanGenomeProject(HGP)wasaninternationalprojectled
bytheUSDeptofEnergy,NationalInstitutesofHealth&
WelcomeTrust(UK)launchedin1990tomapandsequencethe
humangenome.
TheannouncementofthedraftfullDNAsequenceon26June,
2000willbeahistoricalday.
Somepeoplesaid,itwillberememberedasthedaywhenwelearnt
“whatitmeanstobeahuman”.

3. Theinitialproposalforthe“HumanGenomeProject”isconsideredto
bethe1986editorialbyRenatoDulbecco.
Hesuggestedthatthefundamentalproblemsrelatedtocancercanbe
addressedbydeterminingthesequenceoftheentiregenome.
Sincetheneffortshavebeencontinuedatagloballeveltostudythe
entiregenomeofhumanandanumberofothermodelorganisms.
Alreadythecompletegenomeofover20organismswassequenced
beforescientistsachievedthefulldrafthumansequence.
Themoleculardissectionofthegenomesfromsomanyspecieshas
unquestionablychangedthescopeforscientificandmedicalresearch.

4. SalientFeaturesofHumanGenome:
Humangenomeconsiststheinformationof24chromosomes(22
autosome+Xchromosome+oneYchromosome);inHomosapiens
2n=2x=46
Thehumangenomecontainsover3billionnucleotidepairs.
Humangenomeisestimatedtohaveabout30,000genes.
Averagegeneconsistsof3000bases.

5. Butsizesofgenesvarygreatly,withthelargestknownhuman
geneencodingdystrophincontaining2.5millionbasepairs.
Onlyabout3%ofthegenomeencodesaminoacidsequences
ofpolypeptidesandrestofitjunk(repetitiveDNA).
Thefunctionsareunknownforover50%ofthediscovered
genes.

6. Therepetitivesequencesmakeupverylargeportionofhuman
genome.
Repetitivesequenceshavenodirectcodingfunctionbutthey
shedlightonthechromosomestructure,dynamicsand
evolution.
Chromosome1hasmostgenes(2968)andYchromosomehas
thelowest(231).
Almostallnucleotidebasesareexactlythesameinallpeople.

7. Genomesequencesofdifferentindividualsdifferforlessthan
0.2%ofbasepairs.
Mostofthesedifferencesoccurintheformofsinglebase
differencesinthesequence.
Thesesinglebasedifferencesarecalledsinglenucleotide
polymorphisms(SNPs).
OneSNPoccursatevery~1,000bpofhumangenome.
About85%ofalldifferencesinhumanDNAsareduetoSNPs.

8. MilestonesofHGP
1986ThebirthoftheHumanGenomeProject.
1990ProjectinitiatedasjointeffortofUSDepartmentof
EnergyandtheNationalInstituteofHealth.
1994GeneticPrivacyAct:toregulatecollection,analysis,
storageanduseofDNAsamplesandgeneticinformation
isproposed.
1996WelcomeTrustjoinstheproject.

9. 1998Celera Genomics (a private company founded by Craig
Venter) formed to sequence much of the human genome
in 3 years.
1999Completion of the sequence of Chromosome 22-the first
human chromosome to be sequenced.
2000 Completion of the working draft of the entire human
genome.
2001Analysis of the working draft are published.
2003HGP sequencing is completed and Project is declared
finished two years ahead of schedule.

10. 1.ToidentifyallthegenesinhumanDNA.
2.Todevelopageneticlinkagemapofhumangenome.
3.Toobtainaphysicalmapofhumangenome.
4.Todeveloptechnologyforthemanagementofhumangenome
information.
Goals of human genome project

11. 5.Toknowthefunctionofgenes.
6.Determinethesequencesofthe3billionchemicalbasepairs
thatmakeuphumanDNA.
7.Storethisinformationinpublicdatabases.
8.Developtoolsfordataanalysis.
9.Transferrelatedtechnologiestotheprivatesectors.

12. Shotgun DNA sequencing
Shotgunsequencingisanapproachusedtodecodean
organism'sgenomebyshreddingitintosmallerfragments
ofDNA whichcanbesequencedindividually.
Thesequencesofthesefragmentsarethenordered,based
onoverlapsinthegeneticcode,andfinallyreassembled
intothecompletesequence.

13. The output from an automated DNA sequencing robot
Eachpeakshowsthepresenceofaparticularbase.The
sequenceofbasesinagivenstretchofDNAcanthereforebe
readfromtheorderofthepeaksalongthetrace.
The
Sanger
Institute,
Wellcome
Images

14. Fromtheverybeginning,theGenomeProjecthasbeeninthe
limelightforvariousreasonsincludingthepotentialbenefitssuch
as:
1.MedicalProspects
2.ScientificProspects
3.AgriculturalProspects
4.EnvironmentalApplications
5.UseinForensicScience
6.EconomicImplications

15. MedicalProspects
ThecentralthrusttotheHumanGenomeProjectwasundoubtedlyfor
biomedicalresearch.
Alreadythegenesformanydiseasesincludingforexample,various
cancers,Alzheimer’sdisease,andpolycystickidneydisease,havebeen
identified.
Genomicsequencingallowsrapidandaccuratediagnosisforindividuals.
Initiallythesequencingofhumangenomehasledtoashifttowards
preventivemedicineratherthancurative,becausefurtherresearchis
neededtodeveloptherapies.

16. Earlierdetectionofgeneticpredispositionstodiseasecanbe
usedforlateonsetofgeneticallyinheriteddiseases.
Suchdiscoverieswillenableustoworkoutwhichcombinationsof
genesandenvironmentalfactorswillleadtodisease.
Inadditiongenetherapyisbeingtested.
Otheradvantagesofthesequencingincludegenetictestingand
screening,anditsuseinreproductivetechnologiesfor
preimplantationdiagnosis.

17. Knowingthegeneshelpsinunderstandingthemolecularbasisof
medicine.
Sothatdrugscanbedesignedtotargetthecauseofthe
disease.
Thedrugscanbedesignedforspecificindividuals,
pharmacogenics,“customdrugs”,whichwillchangetheprescription
ofdrugs.
Alsointheassessmentofhealthdamageandriskscausedby
exposuretomutagenicchemicalsandcancercausingtoxins,to
reducethelikelihoodofheritablemutations.

18. Scientific Prospects
Oneoftheidealsofscienceisfreedomforself-understanding.
Thesequencingofthegenomewillprovidenewcluesonhowwe
evolved.
Itwouldhelpustounderstandwhatitmeanstobeahumanfrom
differenthistoricalperspectivesofbioarchealogy,anthropology,
evolution,andhumanmigration.
BroaderquestionsontheevolutionofHomoSapiens,theextentof
humandiversity,howmuchwesharewithnatureorwhatmakesus
differentfromotherswillbeansweredbycomparisonsofgenomes.

19. Environmental Applications
TakingintoaccountthepotentialadvantagesoftheHGP,similar
publicandprivate-fundedprojectswerestartedtosequencethe
genomesofvariousmicrobes.
Besidestheirroleindisease,afurtherreasonisthatmicrobes
playacriticalroleinbiogeochemicalcycles.
Annotationandanalysisofmicrobialgenomeswillhelpin
identifyingandharnessingtheircapabilitiestoaddressthe
environmentalproblems,theiruseinenergyproductionthatcan
beusedasbiofuels,asananswertothelimitednaturalresources
available.

20. Use in Forensic Science
Forensicscienceisoneofthefieldsthatisalsoexpectedtobe
benefitedfromthegenomesequencing,especiallyinthe
identificationofcriminalsandvictimsofsometragedy.
Thegenomeprojectisexpectedtoprovidecluestoexaminethe
contextandtheenvironmentinwhichthescienceandthelawmeet.
TheotherexamplesofDNAusesforforensicidentificationinclude,
identifyingendangeredandprotectedspecies,helpinestablishing
relationshipswithfamilymembers.

21. Economic Implications
TheHumanGenomeProjectisthelargestsinglebiological
projecteverundertaken.
Forexample,justthegovernmentbudgetintheUnitedStates
startedwithUS$28millionin1988,andwasatUS$361million
in2000,approximatelyatwelve-foldincreaseinthefunding.
Othergovernmentsalsospentmuch,andprivateinvestmentat
leastwasequaltothis.

22. Suchahugemonetaryinvestmentinitselftestifiestothe
foreseenbenefitsoutofthesequencing.
Neverthelessthecost-effectivenessoftheprojectwasunder
criticismespeciallyinearlyyears.
Thecritiquesareapprehensiveaboutexistinggapsinthegenome.
ThequestionsofpatentingofDNA,andgenesbygovernmentsand
privatecompanies,intellectualpropertyrightsandbenefit-sharing,
havebeenparticularlydebated,andcanbeseeninthepublic
announcementsoffirstdrafthumangenomesequenceinyear2000.

23. ETHICAL LEGAL AND SOCIAL ISSUES OF HGP

24. EthicalConcernsofhumangenomeprojectsuchas
1.Beneficence,
2.Donoharm,
3.Humanrights,
4.Animalrights,
5.Authority,
6.Autonomy,
7.Ownership,
8.Justice,
9.Confidentialityandprivacy,
10.Responsibility,
11.Scientistsandsocialduty,and
12.Consequences,
thatwilleffectallparametersoflifeonthisplanet.

25. SincethebeginningoftheHumanGenomeProject,manyethical
questionswereraised.
Recognizingthat,DOEandtheNIHallocated3–5%oftheirtotal
expenditureonHGPfortheELSIarisingoutoftheGenomeProject.
Thisrepresentedtheworld’slargestbioethicsprogram.
TheEuropeanCommissiononlystartedfundingtheHGPwhenit
hadsetupanELSIprogram.
Sincethentherehavebeencontemporaryeffortsgoingonto
answersomeofthebioethicalchallengesoftheHumanGenome
Project.

26. DifferentsectorsofsocietyhavebeeninvolvedintheHGP
1.Ordinarypeople,
2.patients,
3.scientists,
4.industry,
5.governments,
6.legalsystem,
7.regionalandinternationalorganizations,and
8.UnitedNations.

27. (a) Beneficence
Theprincipleofbeneficencesignifiesanobligationtobenefit
othersortoseektheirgoodandithasbeenthefoundationofmany
codes.
ThemotiveoftheHGPisalsobasedontheprincipleofbeneficence
toall,beitmedicalpatients,healthprofessionals,publicinstitutions
orprivatecompanies.
Beneficenceistheimpetusforfurtherresearchintowaysof
improvinghealthandagriculture,andforprotectingtheenvironment.
Beneficencesupportstheconceptofexperimentation,ifitis
performedtoleadtopossiblebenefits.

28. (b) Do no harm
Itisthebasisfortheprinciplesofjusticeandconfidentialityand
philanthropy.
TwomainethicalargumentsintheHumanGenomeProjectrevolve
aroundthemoralconceptofjusticeandconfidentialitythatare
discussedseparately.
(c) Human rights
Insimpleterms,thehumanbodycannotbeusedasanexperimental
“organism”withoutconsent.
Thisisenshrinedincodesgoverningmedicalexperimentation,suchas
theNurembergCodeandtheHelsinkiDeclaration.

29. (d) Animal rights
Ethicalguidelinesforresearchonnon-humananimalsarebased
ontheassertionthat
Animalsaresentient,haveconsciousexperiences,andfeelpain
andsuffering,especiallythevertebrateanimals.
Usuallythebenefitsofdiscoveriestohumansgenerally
overweigh
thesufferingofanimals.
Animalscannotberegardedasmeansofachievingourgoals.

30. (e) Authority
Manypeopleraiseddoubtsaboutwhoshouldbeinvolvedinthe
sequencingofthegenomeandwhoshoulddothework.
Theprojectrequiredamulti-disciplinaryapproachinvolvingmedical
experts,biologists,bioethicists,informationspecialists,computer
expertsandmanyothersfordatabankingandanalysis.
ThemultidisciplinaryauthorizationoftheGenomeProjecthason
onehandrewardeditwithspeedingtheprocess,ontheotherhand
itarousedconflictbetweendifferentgroupsbecauseofthe
inherentinterestsoftheirrespective
fields.

31. (f) Autonomy
Theconceptofautonomyinbioethicsgiveseachindividualthe
recognitionofthehumancapacityforself-determinismand
beingdifferentinspiteofsharingsameDNAwhichisregarded
asa“commonheritage”.
(g) Ownership
Thecompetitionforthegenomesequencingbetweenthe
publicallyfundedGenomeProjectandtheworld’sleading
privatecompanyCeleraGenomicsiswellknown.
Thefearbehindthisistheunwarrantedriskofdata
ownership.

32. (h) Justice
Theothersideofthepossibilityfortransformingmedicineiswho
willactuallybenefit?
Willeveryonehaveaccesstosuchrevolutionizedhealthcare?
Thereisafearthatitmightwidenthegapbetweenrichand
poor.
Inthedevelopingworld,theHumanGenomesequencingmaynot
bethefirstchoiceforbettertreatment,wheremillionsofpeople
donotevenhaveaccesstobasicmedicaltreatment.

33. (i) Confidentiality and privacy
Itwillnotbesurprisingifinthenextfewyearsweallwillbe
abletogetourindividualgenomessequenced.
Theprivacyofthegeneticinformationisreinforcednotonly
becauseofthepresumedprospectsfortheuseofsuch
informationbeyondmedicalreasons,forinstance,discrimination
ofthe“geneticunderclass”atdifferentlevels,

34. (j) Responsibility
Theresponsibilityofuseorthemisuseofthegeneticinformation
isanindividualdecision,butwhatisusefulforonemaynotbe
usefulforothers.
Thedefinitionof“misuse”isalsodebatable.
(k) Scientists and social duty
Thescientificcommunityhastobearthemoralresponsibilityfor
usingverypowerfulknowledge,asagreedintheUNESCO
DeclarationontheHumanGenomeandHumanRights.
Buttherealwaysliesthedangerofmisusingscientificfreedom.

35. (l) Consequences
TheconsequencesoftheHGPareaffirmativeonlywhenusedina
properway,forthewellbeingofallofhumanity.
Thetremendouspotentialofthetechnologyisunquestionable.
Wehavetousetheprecautionaryprincipleapproach,whichsayswe
needtobeverycarefultoavoidharm.
HumanGenomeOrganisation(HUGO)hasproposedguidelinesto
addresssomeoftheethicalandlegalrequirementsrelatedtoHGDP.
TheHGDPmakesusconsiderourrootsandtheirimportance(ornot)
inmodernsociety.