THE HUMAN GENOME PROJECT

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THE HUMAN GENOME PROJECT
Adam Zahr Juliana Elawar Andrew Raupp

• The gene is by far the most sophisticated
  program around.
• Bill Gates, CEO Microsoft

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Mendel The Father of Genetics

• Made brilliant insights into heredity.
• Began classical experiments into heredity
  involving pea plants beginning in 1854.
• Established Principle of Segregation as well as
  the concept of dominant and recessive traits.

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Questions surround Mendels
findings

• Mendels ideas seem obvious today. This was not
  the case in the past. No one had ever heard of a
  gene in Mendels time.
• Biologists previously failed to distinguish
  between heredity and development.

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The Discovery DNA of
In 1869 Friedrich Miescher isolated a
substance that he called nuclein from
pus-soaked bandages.

• Inheritance insures the continuity informed
  from generation to generation that lies even
  deeper than the chemical molecule. It lies the
  structuring of atomic groups. In this sense, I
  am a supporter of the chemical heredity theory.

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The Transforming Principle

• Walter Sutton and Theodor Boveri independently
  came to the conclusion that chromosomes must be
  the factors that Mendel believed are passed on
  from parents to offspring.

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The Transforming Principle

• Their ideas were later confirmed by Thomas Hunt
  Morgan. Using the Drosophila melanogaster (fruit
  fly) Morgan and his students (Morgans boys)
  found a correlation between the gene for eye
  color with the X chromosome.

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Oswald Avery Experiment
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The Secret of Life

• James Watson and Francis Crick discovered the
  double helix in 1953.

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Advances in Genetics

• In 1973 Recombinant DNA procedures were
  introduced by Stanley Cohen and Herb Boyer
• At same time, Fred Sanger and Walter Gilbert
  developed a new way to determine the order of
  bases along the DNA molecules.
• The method was called Chain Termination Method

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Genetic Sequencing

• Humans could now sequence the genome of any
  organism.
• By the early 1980s. viral genome containing more
  than 100,000 bases and bacterial genomes
  containing more than a million bases become
  realistic objectives.
• Scientists began pondering the possibility of a
  Human Genome Project

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Genetic Sequencing

• Currently, 100 prokaryotic and 18 eukaryotic
  genomes have been sequenced
• As more genetic information becomes available,
  pieces of our evolutionary past will come
  together.

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Comparing the Human Genome with other Genomes

• Gene numbers of different species
• Humans 31,000
• Thale cress 26,000
• Nematode worm 18,000
• Fruit fly 13,000
• Yeast 6,000
• Tuberculosis microbe 4,000

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Comparing the Human Genome with that of Mus
musculus (mouse)

• The human genome has about 400 million more
  nucleotides than the mouse.
• Humans and mice genetically diverged about 75
  million years ago
• The human and the mouse genomes both have
  approximately 30,000 genes . (99 identical)
• There are only three hundred genes unique to
  either organism

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Comparing the Human Genome with that of Mus
musculus (mouse)

• Most of the nearly 150 genes unique to mice are
  linked with the sense of smell, which is highly
  developed in rodents, and with reproduction. Mice
  produce frequent large litters.
• The genomes of humans and mice are so similar
  that the best explanation for why a mouse
  develops into a mouse and not a human is that the
  genes are expressed at different times and
  possibly in different tissues.

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Comparing the Human Genome with that of Pan
troglodytes(Chimpanzees)

• Humans and chimps diverged from a common ancestor
  only about 5 million years ago.
• Preliminary sequence comparisons indicate that
  chimp DNA is 98.7 identical with human DNA. If
  just the gene sequences encoding proteins are
  considered, the similarity increases to 99.2.

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How could two species differ so much in body and
behavior, and yet have almost equivelent sets of
genes?

• Observations reveal that chimp and human genomes
  show very different patterns of gene
  transcription activity, at least in brain cells.
• Humans have one less chromosome than chimpanzees,
  gorillas, and orangutans. Its not that we have
  lost a chromosome. At some point in time, two
  mid-sized ape chromosomes fused to make what is
  now human chromosome 2, the second largest
  chromosome in our genome.

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Applications of Genetic Information
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Ways of gathering genetic information

• One can gather genetic information in various
  ways. It can be acquired via a family's medical
  history or during a routine physical exam.
  Genetic info can also be gathered through common
  lab tests that measure the production of certain
  substances. The most accurate approach is
  through DNA. Different genetic tests identify
  explicit DNA characteristics.

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Ethical and Societal ImplicationsGenetic
Discrimination

• Examples of discrimination workplace, insurance,
  military, etc
• A survey conducted in 1996 of individuals at risk
  of developing a genetic disorder, showed that
  they were discriminated against over 20 percent
  of the time.
• Another recent study conducted by genetic
  counselors showed that over 500 people lost their
  job based upon new knowledge of their genetic
  info to their employers. In 1995 a poll showed
  that over 80 percent of Americans were at least
  somewhat concerned that genetic information would
  get into the wrong hands and would either cost
  them more in insurance money or an employment
  opportunity.

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Ethical and Societal Implications

• An 18-year-old man, who could potentially develop
  Huntington's disease from one of his parents
  refused to get tested. Why? He wanted to serve
  in the United States Armed Forces and was afraid
  that the recruiters would prevent him from
  joining. This would ultimately keep him out of
  the Persian Gulf War. When the question
  regarding hereditary disorders on his application
  asked about Huntington's disease in his family
  medical history he replied with an answer of
  no.

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Ethical and Societal ImplicationsGene Patenting

• In June 2000, the human genome was mapped and
  thousands of investors, scientists, etc.
  requested patents for genes and varying pieces of
  gene sequences.
• The total number of "working" human genes is
  estimated to be somewhere between 25,000 and
  100,000, it represents approximately three and a
  half percent of the total human genome. The rest
  of the genetic information is made up of junk
  DNA. The ownership of information now may greatly
  payoff for the person that owns it later
  because when the function is eventually
  determined it may be of great importance.

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Ethical and Societal ImplicationsResulting Laws

• The need for federal protection has been
  recognized by Congress with the introduction of
  numerous bills with bipartisan support. Three
  stand-alone bills have been introduced that amend
  existing civil rights or labor laws to protect
  workers against employment discrimination based
  on genetic information (S. 1045, Sen. Daschle
  H.R. 2275, Rep. Lowey H.R. 2215, Rep. Kennedy).
  Two additional bills have been introduced that
  include worker protections against discrimination
  based on genetic information, as part of broader
  proposals addressing the use of genetic
  information (S. 422, Sen. Domenici H.R. 2198,
  Rep. Stearns). (4)

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Ethical and Societal ImplicationsResulting Laws

• In January 2001, the United States Patent and
  Trademark Office released an 1100 page set of
  guidelines aimed at stopping companies from
  patenting genes that were sequenced before
  creating a particular applied use for them.

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The human genome can teach us

• About basic process of life
• About genetic diseases that affect some people
  and not others
• And gives us an insight on how to treat
  devastating diseases like Alzheimers and cancer.

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Why study the HGP?

• The identification of genes will aid in the
  diagnosis, treatment, and prevention of many of
  our more common ailments, including high blood
  pressure, heart disease, diabetes, mental
  illness such as schizophrenia, and some types of
  cancers.

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Insulin Gene

• The insulin gene was the first pharmaceutical
  product made using recombinant DNA technology.

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a1 Milano gene

• The normal gene has gone through a point mutation
  which caused a different amino acid to be added.
  The new amino acid causes the whole protein to
  fold differently
• In the case of this mutation, the new protein
  became more effective.

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Cancer

• One in 4 people will die of cancer, and
  researches all over the world are competing in
  the race to beat such a terrible disease. Some
  researches believe that the cure for cancer lies
  hidden in our genome.

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Oncogenes

• RAS malfunction is one of the most common causes
  of cancer since it sends signal for division.
  When RAS goes berserk, the p53 gene, which is a
  tumor suppressant gene, activates defensive
  enzymes that stop incorrect growth signals sent
  by the RAS oncogene.

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Gene Therapy

• Gene therapy an approach where the gene is the
  drug, and we are trying to deliver the drug, or
  gene, to a particular part of the body of
  patients with the gene defected.
• Uses p53 protein to make cancerous cell to commit
  apoptose.

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Li-Fraumeni syndrome

• A person that inherits only one functional copy
  of the p53 gene from their parents, then they are
  predisposed to cancer and usually develop several
  independent tumors in a variety of tissues in
  early adulthood

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Gene Therapy

• Gene therapy an approach where the gene is the
  drug, and we are trying to deliver the drug, or
  gene, to a particular part of the body of
  patients with the gene defected

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Have We Found The Fountain Of Youth?

• Cell can only divide so many times before it
  cannot do so any more because the telomere at end
  of chromosome becomes used up every time the cell
  divides. In other words,
• aging and the age
• people live until is
• written in our
• genes.

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How can the HPG impact us in the near future?

• Pharmacists are already working on the
  development of drugs tailored to each
  individual's genetic makeup. In other words,
  doctors will be able to pick the medication that
  would work best for an individual. This should
  optimize the treatment while reducing the side
  effects

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How can the HPG impact us in the near future?

• Currently, however, we do not have the technology
  available to replace malfunctioning gene.