human genome project (fcc)
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Genome
The total set of molecules of inheritance ina particular organelle, cell or organism
Determination of a entire genome sequenceis a prerequisite to understanding the complete
biology of an organism.
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The history of science through the last millennium(20 th century) is characterized by an exponential rateof expansion especially in the field of biology. One of the most ambitious project in biology launched in thelast decade of last millennium was Human Genomeproject. The ultimate anatomic basis forhuman/medical genetics , the DNA sequence isprovided by HGP. This is perhaps the second bestachievement by man after landing on the moon.
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S tructural: construction of sequencedata and gene map.
Functional: functions of genes, and theirregulation and products.
Comparative: compare genes from differentgenomes to elucidate functional and evolutionalrelationship.
Genomics
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HGPy
199 0 2003y Originally planned for 15 yearsy Department of Energy & National Institute of Health
USAy Welcome Trust UKy France, Germany, Japan, China
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GOALS
y Determine the sequences of the chemical base pairsthat make up human DNAy Identify all the genes in human DNAy S tore this information in databasesy improve tools for data analysisy Transfer related technologies to the private sectory Address the ethical, legal, and social issues (EL SI) that
may arise from the project.y Two scientific and technologic revolutions, the biological
revolution and the information revolution, converged inthe human genome initiative
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HGP
y Though the HGP is finished, analyses of the data willcontinue for many years.
y Completion of the human genome project provides a
source book of the human that will be the bases forstudy in human biology and medicine for a long timeto come. When all the genes have been found, wecertainly still will not know, for most of them, their
function even in solo, let alone in concert with therest of their genome.
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y 3164 .7 million (~3 billion)chemical nucleotide bases (A,C, T, and G).
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y Almost all ( 99 .9% ) nucleotide bases are exactly the same inall people
y The total number of genes is estimated at 30,000y Chromosome 1 has the most genes (2 968 ), and the Y
chromosome has the fewest (23 1 ).y The average gene consists of 3000 bases (variable)
largest known human gene being dystrophin at 2. 4 million bases.y Less than 2 % of the genome codes for proteins.y The functions are unknown for over 5 0% of discovered
genes
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y Genes appear to be concentrated in random areas along thegenome, with vast expanses of noncoding DNA between.
The human genome's gene-dense "urban centers" G and C (light bands)In contrast, the gene-poor "deserts" are rich in A and T (dark bands).
y R epeated sequences that do not code for proteins ("junk DNA")make up at least 5 0% of the human genome.
y R epetitive sequences are thought to have no direct functions.y S tretches of up to 30,000 C and G bases repeating over and over
often occur adjacent to gene-rich areas, forming a barrierbetween the genes and the "junk DNA." These CpG islands arebelieved to help regulate gene activity.
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y Unlike the human, many other organisms' genomes are moreuniform, with genes evenly spaced throughout.
y
Humans have on average three times as many kinds of proteinsas the fly or worm because of m R NA transcript "alternativesplicing" and chemical modifications to the proteins. This processcan yield different protein products from the same gene.
y Humans share most of the same protein families with worms,flies, and plants, but the number of gene family members hasexpanded in humans, especially in proteins involved indevelopment and immunity.
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y The human genome has a much greater portion ( 5 0% ) of repeat sequences than the mustard weed ( 11% ), theworm (7 % ), and the fly (3 % ).
y Although humans appear to have stopped accumulatingrepeated DNA over 5 0 million years ago, there seems tobe no such decline in rodents. This may account for someof the fundamental differences between hominids androdents, although gene estimates are similar in thesespecies.
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y About 1 .4 million locations where single-base DNAdifferences ( SNPs) occur in humans.
y This information promises to revolutionize the processesof finding chromosomal locations for disease-associatedsequences and tracing human history.
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What Does the Draft Hum an Geno m e Seq u ence Tell Us?
y The ratio of germline (sperm or egg cell) mutations is 2: 1in males vs females. R esearchers point to several reasonsfor the higher mutation rate in the male germline,
including the greater number of cell divisions required forsperm formation than for eggs.y S iblings by 1 to 2 million bases, ~ 99 .98% identical, with
coding regions 99 .99999% identical.y Unrelated humans by 6 million bases, ~ 99 .8% identical
overall, with coding regions 99 .9999% identical.
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Chimpanzees by about 100Chimpanzees by about 100million base pairs ~98%million base pairs ~98%
identicalidentical
Chimpanzees by about 100Chimpanzees by about 100million base pairs ~98%million base pairs ~98%
identicalidentical
Baboons by about 300 millionBaboons by about 300 millionbase pairs ~92% identicalbase pairs ~92% identical
Baboons by about 300 millionBaboons by about 300 millionbase pairs ~92% identicalbase pairs ~92% identical
Ou r Nearest Relatives18
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Ou r Nearest Relatives
M ice by about 2. 8 billion bases, but
coding regions are~9 0% identical
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HGP
y B y licensing technologies to private companies andawarding grants for innovative research, the projectcatalyzed the multibillion-dollar U. S . biotechnology
industry and fostered the development of new medicalapplications.
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HGP - Benefits
Molec u lar Mediciney Improved diagnosis of diseasey Earlier detection of genetic predispositions to diseasey Rational drug designy Gene therapy and control systems for drugsy Pharmacogenomics "custom drugs"
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HGP - Benefits
y Shift of paradigm from medical genetics to geneticmedicine. The method developed by the HGP will allowthe rapid and economical generation of information on
the genomes of individuals. This information wouldwiden the gap between what we know how to diagnoseand what we know how to treat, between what we whatwe can diagnose in the pre-symptomatic state and what
we can prevent. It is going to increase gap in what wethink we know and what we really know.
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HGP - Benefits
Energy and Environ m ental App licationsy U se microbial genomics research to create new energy
sources (biofuels)y U se microbial genomics research to develop
environmental monitoring techniques to detect pollutantsy U se microbial genomics research for safe, efficient
environmental remediationy U se microbial genomics research for carbon sequestration
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HGP - Benefits
Risk Assess m enty A ssess health damage and risks caused by radiation
exposure, including low-dose exposures
y A ssess health damage and risks caused by exposure tomutagenic chemicals and cancer-causing toxins
y Reduce the likelihood of heritable mutations
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HGP - Benefits
Bioarchaeology, Anthro p ology, Evol u tion, and Hum anMigrationy S tudy evolution through germ line mutations in lineagesy
S tudy migration of different population groups based onfemale genetic inheritancey S tudy mutations on the Y chromosome to trace lineage
and migration of malesy
Compare breakpoints in the evolution of mutations withages of populations and historical events
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HGP - Benefits
DNA Forensics (Identification)y Identify potential suspects whose DN A may match
evidence left at crime scenesy
Exonerate persons wrongly accused of crimesy Identify crime and catastrophe victimsy Establish paternity and other family relationshipsy Identify endangered and protected species as an aid to
wildlife officials (could be used for prosecutingpoachers)
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HGP - Benefits
DNA Forensics (Identification)y Detect bacteria and other organisms that may pollute air,
water, soil, and food y Match organ donors with recipients in transplant
programsy Determine pedigree for seed or livestock breeds
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HGP - Benefits
Agric u lt u re, Livestock Breeding, and Bio p rocessingy Disease-, insect-, and drought-resistant cropsy Healthier, more productive, disease-resistant farm
animalsy More nutritious producey Biopesticides
y Edible vaccines incorporated into food productsy New environmental cleanup uses for plants like tobacco
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E thical, Legal, and Social IssuesE thical, Legal, and Social Issues
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Ethical, Legal, and Social Iss u es
y The existence of genetic information with respect toindividuals and the human population as a whole will
have a profound impact on our day-to-day lives and maywell change how we regard ourselves and one another.
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Social, Legal and Ethical Iss u es33
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Ethical, Legal, and Social Iss u es
y Ethical iss u es are generally defined as those raisingquestions concerning what is moral or right.
y Legal iss u es are those concerning the protections that
laws or regulations should provide.y Social iss u es are concerned with how events may affect
society as a whole and individuals in society.
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Fairness in the Use of Genetic Infor m ation
y Who should have access to this information?Emp loyersIns u rersSchoolsCou rtsAdo p tion agenciesMilitary
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When a patient tests positive for a gene linked to risk of disease, does the physician (or the patient) have aresponsibility to inform the patients relatives of their ownrisks?
Can a physician over the patient's objection reveal a positivetest result for an inherited disorder to the patient's children,on the ground that disclosure is necessary to enable thechildren to protect themselves
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Privacy (contin u ed)
y Analysis of one s own genetic makeup could reveal thegenetic makeup of parents and siblings, including, forexample, unsuspected information about paternity.
y How willing would people be to share this knowledgeand, if they decided to withhold it, how would they beaffected by living with the secret?
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Discri m ination
y M any people who reveal genetic test results to theirhealth or life insurers report that they are deniedinsurance or that their policies are canceled.
y
Already a company in Great B ritain has applied for apatent on a device that can apparently detect differentforms of over 2, 5 00 genes said to be associated with traitsincluding behavior and intelligence
y R acial discrimination!!!!!
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Gene Thera p y
y There are two routes to replacing a faulty gene.
Ger m line thera p y, has the goal of replacing a harmful gene ina fertilized human egg with a properly functioning gene that
would be passed on to future generations.
Som atic gene thera p y, aims to replace the gene in targetorgans or tissues of an adult, so as to fix the symptoms in thatindividual but not in the next generation.
y Germ line therapy has the more profound ethical, legaland social implications.
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Gene Thera p y
y Defining what is normal, what is a disability, and what is adisease?
y
Which of the genetic variations within a population oughtto be eradicated, if any?
y In trying to eradicate a certain variation, are wedemeaning those in the population who currently carrythe gene?
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Som e arg u e that if
the technology isadvanced in orderto eradicate so m ediseases, it willinevitably be u sedby p arents wishingto "enhance" theirchildren, givingthe m the genes forraven black hairand bl u e eyes or
athletic p rowess .
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Application of B iology and M edicine:
Convention on Hum an Rights and Bio m edicine. Article 13 of theConvention states that
An intervention seeking to modify the human genome mayonly be undertaken for preventive, diagnostic ortherapeutic purposes and only if its aim is not tointroduce any modification in the genome of any
descendants."
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y On a more individual level, the results of the HGP mightencourage people to view themselves as being whollyunder the control of their genes. What has traditionally
been viewed as the human spirit might in future beseen as limited by pre-programming at birth.
Legal Iss u es46
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Conce p tu al and Philoso p hical I mp lications
y R egarding human responsibility, free will vs geneticdeterminism, and concepts of health and disease.
y Do people's genes make them behave in a particular
way? y Can people always control their behavior? y What is considered acceptable diversity? y Where is the line between medical treatment and
enhancement?
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y "I just can't indicate how silly I think it [the sanctity of the human gene pool is. I mean, sure, we have great
respect for the human species. We like each other.We'd like to be better, and we take great pleasure ingreat achievements by other people. B ut evolution canbe just damn cruel, and to say that we've got a perfect
genome and there's some sanctity to it, I'd just like toknow where that idea comes from. It's utter silliness.And the other thing, because no one really has theguts to say it, I mean, if we co u ld m ake better h um an
beings by knowing how to add genes, why sho u ldn'twe do it?"
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y Lee Silver celebrates the coming future of "reprogenetic"human enhancement, in which the health, appearance,personality, cognitive ability, sensory capacity, and life-span of our children all become artifacts of geneticmanipulation, literally selected from a catalog.
y S ilver acknowledges that the costs of these technologieswill limit their full use to only a small portion of people,
so that over time society will segregate into the"Gen R ich" and the "Naturals .
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y "The Gen R ich - who account for 1 0 percent of population - allcarry synthetic genes... that were created in the laboratory
...All aspects of the economy, the media, the entertainmentindustry, and the knowledge industry are controlled bymembers of the Gen R ich class...
y Naturals work as low-paid service providers or as laborers, andtheir children go to public schools... If the accumulation of genetic knowledge and advances in genetic enhancementtechnology continue ...
y the Gen R ich class and the Natural class will become...entirelyseparate species with no ability to cross-breed, and with asmuch romantic interest in each other as a current humanswould have for a chimpanzee."
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METAMAN: The Merging of Hum ans and Machines into a Global Sup erorganis m :"
Dr. Stock
y "B y applying biological techniques to embryos and then to the reproductiveprocess itself, M etaman will take control of human evolution.. Once peoplebegin to reshape themselves through biological manipulation,...the definitionof "human" begins to drift. Altering even a small number of the key genesregulating human growth might change human beings into something quite
different...Competitive pressures withinM
etaman will ensure the spread of any useful ways of significantly enhancing human capabilities. Populationsthat adopt such techniques will generally outdistance those that do not, justas has been the case with other technologies. The computer has become anecessity for modern society, and if a process were developed to triplehuman intelligence or to enable people to get along with no sleep, these toowould soon become 'necessities'. Such changes will not be painless. Like allmajor developments, they will cause great stresses within society. B ut askingwhether such changes are 'wise' or 'desirable' misses the essential point thatthey are largely not a matter of choice; they are the unavoidable product of the technological advance intrinsic to M etaman." (pp 168 -199 ).
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