Uses of Genomic Information in the Diagnosis of Disease

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Uses of Genomic Information in the Diagnosis of
Disease
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What is Genomics?

• Genetics is the study of inheritance or the way
  traits are passed down from one generation to
  another
• Genes have the information to make proteins which
  direct cell activities and functions and
  influence traits such as hair and eye color
• Approximately 30,000 genes in the human DNA
• Genomics is a newer term describing the study of
  all of a persons genes and the interactions of
  those genes with each other and with the
  environment

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Importance of Genomics

• Genomics have a role in 9 of the 10 leading
  causes of death in the US
• http//www.cdc.gov/nchs/fastats/deaths.htm
• All humans have 99.9 identical genetic makeup
• The remaining 0.1 difference may provide useful
  information about diseases
• The goal of genetics is to show why some people
  get sick from certain infections and
  environmental changes while others do not.

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Human Genome Project (HGP)

• A 13 year project where all of the genes in the
  human DNA were discovered
• Determined the sequences of approximately 3
  billion chemical base pairs that make up the
  human DNA
• Completed in 2003 by the U.S. Department of
  Energy and the National Institutes of Health with
  help from many other countries including Japan,
  Germany and France

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What are genetic disorders?

• A disease caused in whole or in part by a
  variation or mutation of a gene
• Researchers are discovering that nearly all
  diseases have a genetic component

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What are genetic disorders?

• Some are caused by a mutation in the gene or
  group of genes in a persons cells
• These may be random or from environmental
  exposure such as cigarette smoke
• Others are hereditary
• the mutated gene is passed down through the
  family
• Most are multifactorial inheritance disorders
• -caused by a combination of small variations in
  genes, often connected with environmental factors

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Three Categories of Genetic Disorders

• 1) Single Gene Disorders
• Caused by a mutation in a single gene. The
  mutation may be present on one or both
  chromosomes
• Such as Sickle cell disease, cystic fibrosis and
  Tay-Sachs
• 2) Chromosome Disorders
• -caused by an excess or deficiency of genes on
  the chromosomes or structural changes within
  chromosomes
• -Down syndrome

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Three Categories of Genetic Disorders

• 3) Multifactorial Inheritance Disorders
• -caused by a combination of small variations of
  genes
• -heart disease, most cancers, and behavioral
  disorders such as alcoholism, obesity, mental
  illness, and Alzheimers disease are examples

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Genetic Testing

• Today more than 900 genetic tests are available.
  
• There are also suseptability tests which can
  determine an estimated risk for developing the
  disease
• List of common tests available
  http//www.ornl.gov/sci/techresources/Human_Genome
  /medicine/genetest.shtml
• Database for the entire human genome
• www.genome.gov

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Genetic Testing How it Works

• Scientists scan a patients DNA for mutated
  sequences
• The DNA sample can come from any tissue including
  blood
• For some tests, probes, short pieces of DNA, are
  designed with sequences complimentary to the
  mutated sequence.
• The probe will seek its compliment among the base
  pairs and will bind to it and flag the mutation
• Other tests compare the bases in a patients gene
  to that of a normal gene

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Genetic Tests Types Available

• Carrier Screening--
• Identifies unaffected individuals who carry one
  copy of the gene that needs two to express the
  disease
• Preimplantation genetic diagnosis
• embryo from in vitro fertilization is tested
  before implanted in the uterus
• Prenatal Diagnostic Testing
• Newborn screening

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Prenatal diagnostic testingWhat tests show

• Neural tube defects
• Birth defects of the brain or spinal cord
• Chromosomal Abnormalities
• Indicated by abnormal amounts of substances in
  the mothers blood such as alfa-feto protein and
  estriol
• Most fetuses with these abnormalities die before
  birth

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Prenatal diagnostic testingTypes of tests

• Ultrasonography
• Performed before other tests to detect obvious
  structural defects in the fetus
• Chorionic Villus Sampling
• A doctor removes a small sample of the chorionic
  villi, which are small projections that make up
  part of the placenta
• Can be done between 10-12 weeks of pregnancy so
  the diagnosis is earlier

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Prenatal diagnostic testingTypes of tests

• Amniocentesis
• One of the most common prenatal tests
• A sample of amniotic fluid is removed and tested
  for alpha-fetoprotein level

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Amniocentesis
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Epidemiology

• Human Genome Epidemiology
• http//www.cdc.gov/genomics/hugenet/default.htm
• The use of the human genome to study vast groups
  of people
• HGDP
• Human Genome Diversity Project
• Uses genomics to study different diseases
  affected by a persons genes among ethnic groups

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Benefits of Genetic Testing

• Some tests can clarify a diagnosis for a more
  concise treatment
• Other tests can prevent families from having
  children with devastating diseases

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Disadvantages of Genetic Testing

• Commercialized gene tests for adult onset
  disorders and some cancers
• For presymptomatic people at high risk because of
  family medical history
• They only give a probability for developing the
  disorder
• People who carry the mutation may never develop
  the disorder
• Possibility for errors due to contamination or
  misidentification
• Cost can range from hundreds to thousands of
  dollars

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Gene Therapy

• Gene therapy is a technique for correcting faulty
  genes which cause diseases
• Genes are specific sequences of bases that encode
  instructions on how to make proteins which
  perform most cellular functions and make up the
  majority of the cellular structure
• When defective genes encode proteins unable to
  perform properly, genetic disorders can occur

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Methods of Gene Therapy

• A normal gene may be inserted into a non-specific
  location within the genome to replace a faulty
  gene (most common method)
• The abnormal gene can be swapped for a normal
  gene through Homologous Recombination.

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Homologous Recombination

• The process where two homologous chromosomes
  exchange a distal portion of their DNA during
  prophase 1 of meiosis. The two homologous
  chromosomes break and reconnect to the different
  end piece. If they break at the same place in
  the base pair sequence, the result is an exchange
  of genes called genetic recombination. It could
  be as often as several times per meiosis.

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Methods of Gene Therapy

• The abnormal gene can be repaired through
  Selective Reverse Mutation, returning the gene to
  its normal function
• The regulation of a gene, the degree to which it
  is turned on or off can be altered