Genetic Testing: Past, Present, and Future Trends

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Genetic TestingPast, Present, and Future Trends

• Jay Ellison MD,PhD
• December 6, 2008

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DISCLOSURE

• Relevant Financial Relationship(s)
• None
• Off Label Usage
• None

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Outline

• Conditions for which genetic testing is used
• Uses of genetic testing
• Complexities of genetic diseases and tests
• Practical considerations in test ordering
• Information resources
• What the future holds

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Genetic Testing Involves Different Types of
Diseases

• Mendelian disorders
• Rare inherited single-gene diseases
• Chromosomal or genomic disorders
• Structural or numerical abnormalities
• Cancer
• Inherited and acquired genetic changes
• Complex diseases
• Common conditions influenced by multiple genes

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Uses of Genetic Testing

• Diagnostic testing
• Predictive testing
• Carrier testing
• Prenatal testing
• Preimplantation testing
• Newborn screening

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Diagnostic Testing

• Can help make or confirm a diagnosis in a
  symptomatic person.
• A negative test result may or may not rule out a
  suspected disorder.
• A positive result may have implications for other
  family members.
• May elect to have presymptomatic testing (e.g.
  hereditary cancer).

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Predictive Testing

• Generally refers to presymptomatic testing when a
  family member has been diagnosed.
• Counseling is especially important many labs
  require informed consent.
• Need to know the mutation in the family.
• Predictive testing can also be applied to
  genetic risk factors a form of screening.

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Carrier Testing

• Used for recessive or X-linked disorders where
  there is a () family history or a high
  population incidence.
• Examples Jewish diseases, CF
• Helps assess risk of certain disorders in future
  offspring counseling crucial.
• Allows informed reproductive choices.

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Prenatal Testing

• Testing of a fetus known to be at high risk.
• There is some risk to the fetus, so consent and
  counseling are required.
• The familial mutation(s) usually needs to be
  identified.
• Testing for adult-onset conditions is
  controversial.

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Preimplantation Testing

• Involves testing of very early embryos resulting
  from in vitro fertilization.
• An alternative to prenatal testing and pregnancy
  termination.
• Technically very challenging performed at only a
  few centers.
• High cost, not covered by insurance.

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Newborn Screening

• Testing of newborns for disorders where early Dx
  and Rx are of benefit.
• Tests are in general not diagnostic some false
  positives.
• Tests generally measure metabolites or enzymes.
• Performed routinely unless parents refuse.

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Genetic TestingSpecial Considerations

• Complicating features of inherited dzs
• Testing caveats
• Need for patient counseling

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Complicating Features of Inherited Single-Gene
Diseases

• Not everyone with a gene mutation develops
  disease (incomplete penetrance).
• More than one gene may cause a disease.
• A gene may cause more than one disease.
• Inheritance patterns are not always apparent.
• There are implications for family members.

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Genetic Testing Caveats

• Test methods may vary in different labs.
• Test sensitivity is rarely 100.
• Gene variation cant always be distinguished from
  a harmful mutation.
• Interpretation of a test report is not always
  straightforward.
• Insurance companies are sometimes reluctant to
  pay.

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Patient Counseling is an Important Part of
Genetic Testing

• Purpose of testing needs to be defined.
• Will it make a difference in treatment?
• Inheritance pattern and implications for family
  members need to be explained.
• Meaning of a positive or negative result needs to
  be understood.
• Counseling should be given both pre- and
  post-test.

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Practical Considerations Regarding Test Ordering

• What tests are available?
• Where and how is the test ordered?
• What sample is appropriate, and how should it be
  processed?
• Blood
• Fetal cells
• Tumor tissue
• Is informed consent required?

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GeneTestsAn Online Genetic Testing Resource

• Available since 1993, when it was known as
  Helix and was limited to health professionals.
• NIH-funded, run out of the U. of Wash.
• Indispensable tool for practicing clinical
  genetics.

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• To access GeneTests, go to
• www.genetests.org

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New Trends in Genetic Testing

• Increasing number of tests available
• Cost ranges from 300 to gt 3000.
• More tests ordered by non-geneticists.
• Tests are not just for rare disease genes.
• Variants influencing drug response
• Cancer monitoring (tumor markers)
• Tumor gene expression patterns
• Still new hope to correlate with treatment
  response and prognosis.

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New Trends (Cont.)

• Genetic risk factors are being identified.
• Gene variants that dont cause disease, but which
  may increase risk.
• Primary utility is in helping to understand
  pathogenesis.
• Hope is that this type of testing can be used
  predictively.
• Direct-to-consumer testing of these risk factors
  is being offered.
• Concept of Individualized medicine based on
  tests of genetic variants.

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Direct-To-Consumer Testing Is Here
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• Offers testing for 91 conditions and traits, as
  well as ancestry.
• Cost 399
• For more info, go to
• https//www.23andme.com/overview/

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• Tests for over 1 million markers reports on 23
  conditions.
• Customers get written report and phone
  consultation with a genetic counselor.
• Cost 2500, plus 250 yearly fee.
• For more info, go to
• http//www.navigenics.com/

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• Offers complete genome sequencing.
• Would give much more information, e.g. carrier
  status for many diseases.
• Current cost 350,000
• For more info, go to
• http//www.knome.com/

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Future Prospects

• Likely increased use of genetic tests for
  predictive purposes.
• Testing to help devise rational and effective
  treatment plans.
• The thousand dollar genome
• What to do with all the data?
• More tests, not enough geneticists.
• Physicians will need to be educated.