HUMAN GENOME PROJECT (FCC)

8/7/2019 HUMAN GENOME PROJECT (FCC)

1/53

1


2/53

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.

2


3/53

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.

3


4/53

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

4


5/53

HGPy

199 0 2003y Originally planned for 15 yearsy Department of Energy & National Institute of Health

USAy Welcome Trust UKy France, Germany, Japan, China

5


6/53

6


7/53

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

7


8/53

8


9/53

9


10/53

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.

10


11/53

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).

11


12/53


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

12


13/53


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.

13


14/53


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.

14


15/53


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.

15


16/53


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.

16


17/53


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.

17


18/53

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


19/53

Ou r Nearest Relatives

M ice by about 2. 8 billion bases, but

coding regions are~9 0% identical

19


20/53

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.

20


21/53

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"

21


22/53

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.

22


23/53

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

23


24/53

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

24


25/53


26/53

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

26


27/53

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)

27


28/53

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

28


29/53

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

29


30/53

E thical, Legal, and Social IssuesE thical, Legal, and Social Issues

30


31/53

31


32/53

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.

32


33/53

Social, Legal and Ethical Iss u es33


34/53

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.

34


35/53

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

35


36/53

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

36


37/53

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?

37


38/53

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!!!!!

38


39/53

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.

39


40/53

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?

40


41/53

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 .

41


42/53

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."

42


43/53

43


44/53

44


45/53


46/53

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


47/53

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?

47


48/53

48


49/53

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?"

49


50/53

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 .

50


51/53

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."

51


52/53

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 ).

52


53/53

53

HUMAN GENOME PROJECT (FCC)

Documents

Transcript of HUMAN GENOME PROJECT (FCC)