Human Genome Project and Genetic Testing

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Human Genome ProjectHuman Genome Project

and Genetic Testingand Genetic Testing



What is Human Genome Project?What is Human Genome Project?

It was an international scientific research project with aIt was an international scientific research project with aprimary goal to determine the sequence of chemical baseprimary goal to determine the sequence of chemical basepairs which make up DNA and to identify the approximatelypairs which make up DNA and to identify the approximately25,000 genes of the human genome from both a physical25,000 genes of the human genome from both a physicaland functional standpoint.and functional standpoint.

The project began in The project began in 19901990 initially headed byinitially headed by James D. James D.WatsonWatson at the U.S. National Institutes of Health.at the U.S. National Institutes of Health. A workingA workingdraft of the genome was released in 2000 and a completedraft of the genome was released in 2000 and a completeone in 2003, with further analysis still being published. Aone in 2003, with further analysis still being published. Aparallel project was conducted by the private companyparallel project was conducted by the private companyCelera Genomics.Celera Genomics. Most of the sequencing was performed inMost of the sequencing was performed inuniversities and research centers from the United States,universities and research centers from the United States,

Canada and Britain.Canada and Britain. The mapping of human genes is anThe mapping of human genes is animportant step in the development of medicines andimportant step in the development of medicines andother aspects of health care.other aspects of health care.



““Objective”Objective”

While the objective of the Human GenomeWhile the objective of the Human Genome

Project is toProject is to understand the geneticunderstand the genetic

makeup of the human speciesmakeup of the human species, the, the

project also has focused on several otherproject also has focused on several othernonhuman organisms such as E. coli, thenonhuman organisms such as E. coli, the

fruit fly, and the laboratory mouse. Itfruit fly, and the laboratory mouse. It

remains one of the largest singleremains one of the largest single

investigational projects in modern science.investigational projects in modern science. The HGP originally The HGP originally aimed to map theaimed to map the

nucleotides contained in a haploidnucleotides contained in a haploid

reference human genome (more thanreference human genome (more thanthree billion).three billion).



““Background”Background”

The Project was the culmination of several years The Project was the culmination of several yearsof work supported by theof work supported by the United StatesUnited States Department of Energy. Particular inDepartment of Energy. Particular in 1984-19861984-1986..

Due to widespread international cooperation andDue to widespread international cooperation and

advances in the field of genomics (especially inadvances in the field of genomics (especially insequence analysis), as well as major advances insequence analysis), as well as major advances incomputing technology, acomputing technology, a 'rough draft' of the'rough draft' of thegenome was finished ingenome was finished in 2000.2000.

InIn May 2006,May 2006, another milestone was passed onanother milestone was passed onthe way to completion of the project, when thethe way to completion of the project, when thesequence of the last chromosome wassequence of the last chromosome waspublishedpublished in the journal Nature.in the journal Nature.



““History”History”

InIn 19761976, the genome of the virus, the genome of the virus Bacteriophage MS2Bacteriophage MS2 waswasthe first complete genome to be determined, by Walterthe first complete genome to be determined, by WalterFiers and his team at the University of Ghent (Ghent,Fiers and his team at the University of Ghent (Ghent,Belgium).Belgium).

““Shotgun method”Shotgun method” - the use of an algorithm that combined- the use of an algorithm that combinedsequence information from many small fragments of DNAsequence information from many small fragments of DNAto reconstruct a genome. (Frederick Sanger, 1980).to reconstruct a genome. (Frederick Sanger, 1980).

in 1998, the announcement by the newly-formed Celerain 1998, the announcement by the newly-formed CeleraGenomics that it would scale up the shotgun sequencingGenomics that it would scale up the shotgun sequencingmethod to the human genome was greeted with skepticismmethod to the human genome was greeted with skepticismin some circles. The shotgun technique breaks the DNA intoin some circles. The shotgun technique breaks the DNA intofragments of various sizes, ranging from 2,000 to 300,000fragments of various sizes, ranging from 2,000 to 300,000

base pairs in length, forming what is called abase pairs in length, forming what is called a DNADNA"library"."library".



““Procedure”Procedure”



Gel ElectrophoresisGel Electrophoresis

It is a techniqueIt is a technique

used for theused for the

separation of separation of

deoxyribonucleicdeoxyribonucleicacid, ribonucleicacid, ribonucleic

acid, or proteinacid, or protein

molecules usingmolecules using

an electrican electriccurrentcurrent applied toapplied to

a gel matrix.a gel matrix.



HGP in “Progress”HGP in “Progress”

A graphical history of the human genome project showsA graphical history of the human genome project showsthat most of the human genome was complete by the endthat most of the human genome was complete by the endof 2003. However, there are a number of regions of theof 2003. However, there are a number of regions of thehuman genome that can be considered unfinished:human genome that can be considered unfinished:

1. the central regions of each chromosome, known as1. the central regions of each chromosome, known ascentromeres, are highly repetitive DNA sequencescentromeres, are highly repetitive DNA sequencesthat are difficult to sequence using currentthat are difficult to sequence using currenttechnology.technology.

2.2. the ends of the chromosomes, called telomeres, are alsothe ends of the chromosomes, called telomeres, are alsohighly repetitive, and forhighly repetitive, and for most of the 46 chromosomemost of the 46 chromosomeends these too are incomplete.ends these too are incomplete.

3. there are several loci in each individual's genome that3. there are several loci in each individual's genome that

contain members of multigene families that are difficult tocontain members of multigene families that are difficult todisentangle withdisentangle with shotgun sequencing methodsshotgun sequencing methods - these- thesemultigene families often encode proteins important formultigene families often encode proteins important forimmune functions.immune functions.







““Estimated Funds”Estimated Funds”

Originally it was estimated that itOriginally it was estimated that it

would cost aroundwould cost around $4 billion but$4 billion but

may well cost more.may well cost more.



““Ethical Issues and Criticisms”Ethical Issues and Criticisms”

HGP is controversial because of theHGP is controversial because of the high costhigh cost and becauseand becausemany critics believe that sequencing a huge amount of many critics believe that sequencing a huge amount of noncoding DNA should have low priority in a time of limitednoncoding DNA should have low priority in a time of limitedfunds for research.funds for research.

It is comparable against other mega-science projects suchIt is comparable against other mega-science projects suchas theas the space station or the superconductingspace station or the superconductingsupercollider: The high cost is not justified. This bigsupercollider: The high cost is not justified. This bigscience vs. little science argument maintains thatscience vs. little science argument maintains thatfunding such large-scale projects takes scarcefunding such large-scale projects takes scarceresources from researchersresources from researchers who may study certainwho may study certainareas of particular interest more efficiently.areas of particular interest more efficiently.

Some critics suggest that the ability to diagnose a geneticSome critics suggest that the ability to diagnose a genetic

disorder before any treatment is availabledisorder before any treatment is available does moredoes moreharm than good because it creates anxiety andharm than good because it creates anxiety andfrustration.frustration. E.g., the mutation in the beta-globin gene thatE.g., the mutation in the beta-globin gene thatresults inresults in sickle cell disease was identified in 1956,sickle cell disease was identified in 1956,but there is no treatment as yet.but there is no treatment as yet.

The The lack of a definitive sequence creates uncertaintylack of a definitive sequence creates uncertainty

about the appropriate definition of "normal," which in turnabout the appropriate definition of "normal," which in turnmakes the discussion of public policy issues difficult.makes the discussion of public policy issues difficult.



Few religious groups in the United StatesFew religious groups in the United States

formally have addressed the specificformally have addressed the specific

ethical and public policy issues raised byethical and public policy issues raised by

the HGP, although there is activethe HGP, although there is activeinterdenominational discussion of issuesinterdenominational discussion of issues

related to human genetics in general.related to human genetics in general.

Public policy debates are enrichedPublic policy debates are enriched

considerably by input from these variousconsiderably by input from these variousgroups.groups.

Of course, like any other issues HGP isOf course, like any other issues HGP is

“playing God.”“playing God.”



““Pictured Ideas”Pictured Ideas”







Genetic TestingGenetic Testing

Genetic testingGenetic testing allows the genetic diagnosisallows the genetic diagnosisof vulnerabilities to inherited diseases, andof vulnerabilities to inherited diseases, andcan also be used to determine a person'scan also be used to determine a person'sancestry.ancestry.

It identifiesIt identifies changes in chromosomes, genes,changes in chromosomes, genes,or proteins.or proteins.

It is "It is "the analysis of RNA, chromosomesthe analysis of RNA, chromosomes(DNA), proteins, and certain metabolites in(DNA), proteins, and certain metabolites inorder to detect heritable disease-relatedorder to detect heritable disease-related

genotypes, mutations, phenotypes, orgenotypes, mutations, phenotypes, orkaryotypes for clinical purposeskaryotypes for clinical purposes " (Holtzman" (Holtzman& Watson 1997). It can& Watson 1997). It can provide informationprovide informationabout a person's genes and chromosomesabout a person's genes and chromosomesthroughout life.throughout life.



““Types”Types”

Newborn screeningNewborn screening: Newborn screening is used just after birth: Newborn screening is used just after birthto identify genetic disorders that can be treated early in life.to identify genetic disorders that can be treated early in life.

Diagnostic testingDiagnostic testing: Diagnostic testing is used to diagnose or rule: Diagnostic testing is used to diagnose or ruleout a specific genetic or chromosomal condition.out a specific genetic or chromosomal condition.

Carrier testingCarrier testing: Carrier testing is used to identify people who: Carrier testing is used to identify people whocarry one copy of a gene mutation that, when present in twocarry one copy of a gene mutation that, when present in two

copies, causes a genetic disorder.copies, causes a genetic disorder. Prenatal testingPrenatal testing:: Prenatal testing is used to detect changes in aPrenatal testing is used to detect changes in a

fetus's genes or chromosomes before birth.fetus's genes or chromosomes before birth. Predictive and presymptomatic testingPredictive and presymptomatic testing: Predictive and: Predictive and

presymptomatic types of testing are used to detect genepresymptomatic types of testing are used to detect genemutations associated with disorders that appear after birth, oftenmutations associated with disorders that appear after birth, oftenlater in life.later in life.

Forensic testingForensic testing: Forensic testing uses DNA sequences to: Forensic testing uses DNA sequences toidentify an individual for legal purposes.identify an individual for legal purposes.

Research testingResearch testing: Research testing include finding unknown: Research testing include finding unknowngenes, learning how genes work and advancing our understandinggenes, learning how genes work and advancing our understandingof genetic conditions.of genetic conditions.



““Sample Procedures”Sample Procedures”



““Cost”Cost”

The cost of genetic testing can range The cost of genetic testing can range

from underfrom under $100(£50) to more$100(£50) to more

than $2,000(£1000),than $2,000(£1000), depending ondepending on

the nature and complexity of thethe nature and complexity of thetest. The cost increases if more thantest. The cost increases if more than

one test is necessary or if multipleone test is necessary or if multiple

family members must be tested tofamily members must be tested toobtain a meaningful result.obtain a meaningful result.



““Risk and Limitations”Risk and Limitations”

The physical risks associated with most genetic tests are very The physical risks associated with most genetic tests are verysmall, particularly for those tests that require only a blood samplesmall, particularly for those tests that require only a blood sampleor buccal smear but The procedures used for prenatal testingor buccal smear but The procedures used for prenatal testingcarry a small but real risk of losing the pregnancy (miscarriage)carry a small but real risk of losing the pregnancy (miscarriage)because they require a sample of amniotic fluid or tissue frombecause they require a sample of amniotic fluid or tissue fromaround the fetus.around the fetus.

Many of the risks associated with genetic testing involve theMany of the risks associated with genetic testing involve theemotional, social, or financial consequencesemotional, social, or financial consequences of the testof the testresults.results.

People may feelPeople may feel angry, depressed, anxious, or guilty aboutangry, depressed, anxious, or guilty abouttheir results.their results. In some cases, genetic testingIn some cases, genetic testing creates tensioncreates tension within a family because the results can reveal information aboutwithin a family because the results can reveal information aboutother family members in addition to the person who is tested.other family members in addition to the person who is tested.

Genetic testing can provide onlyGenetic testing can provide only limited informationlimited information about anabout aninherited condition. The test ofteninherited condition. The test often can't determine if a personcan't determine if a personwill show symptoms of a disorder, how severe thewill show symptoms of a disorder, how severe thesymptoms will be, or whether the disorder will progresssymptoms will be, or whether the disorder will progressover time.over time.

Many people are also concerned about theMany people are also concerned about the privacy implicationsprivacy implications of genetic testimony. In the United States, federal law requiresof genetic testimony. In the United States, federal law requires

that this kind of medical information to bethat this kind of medical information to be kept confidential.kept confidential.



““Ethical Issues and Criticisms”Ethical Issues and Criticisms”

Information from genetic testing can affect the lives of Information from genetic testing can affect the lives of individuals and their families. There are 3 main issuesindividuals and their families. There are 3 main issuesconcerned about genetic testing:concerned about genetic testing:

1.1. PrivacyPrivacy - the rights of individuals to maintain privacy.- the rights of individuals to maintain privacy.Some genetic tests are required or strongly encouraged forSome genetic tests are required or strongly encouraged fordeveloping fetuses and newborn babies. If an infant isdeveloping fetuses and newborn babies. If an infant is

found to be a carrier or likely to develop or be affected byfound to be a carrier or likely to develop or be affected byan inherited disease, these findings may affect the futurean inherited disease, these findings may affect the futureemployability or insurability of the individual.employability or insurability of the individual.

2.2. Informed consentInformed consent - obtaining permission to do genetic- obtaining permission to do genetictesting. One must have knowledge of the risks, benefits,testing. One must have knowledge of the risks, benefits,effectiveness, and alternatives to testing in order toeffectiveness, and alternatives to testing in order to

understand the implications of genetic testing.understand the implications of genetic testing. 3.3. ConfidentialityConfidentiality - acknowledgment that genetic- acknowledgment that genetic

information is sensitive and access should to limited toinformation is sensitive and access should to limited tothose authorized to receive it.those authorized to receive it.



““Pictured Thoughts”Pictured Thoughts”





““FAQ’s”FAQ’s”

““Are genetic tests reliable andAre genetic tests reliable andinterpretable by the medicalinterpretable by the medicalcommunity?”community?”

““Do people's genes make themDo people's genes make them

behave in a particular way?”behave in a particular way?” ““Will HGP deliver a great impact inWill HGP deliver a great impact in

improving the human life?”improving the human life?” ““Who owns and controls geneticWho owns and controls genetic

information?”information?” ““How do we as a society balanceHow do we as a society balance

current scientific limitations andcurrent scientific limitations andsocial risk with long-term benefits?”social risk with long-term benefits?”



ENDENDPrepared by:Prepared by:

Barron, Emmanuel John V.Barron, Emmanuel John V.

Q3AQ3A

*(Words/Phrases/Sentences w/c are bold & has*(Words/Phrases/Sentences w/c are bold & hasblack font represent main ideas)black font represent main ideas)

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Human Genome Project and Genetic Testing