DNA Diagnostics

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DNA Diagnostics

• SF 35
• R. Daniel Gietz Ph.D

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Learning Objectives.

• After this lecture the student should be able to
  
• Understand some the basic principles underlying
  common DNA Diagnostic tests.
• Understand the differences and advantages and
  limitations of each DNA Diagnostic test.
• Appreciate the issues related to DNA testing such
  as presymptomatic testing, insurability and
  testing of children.

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Genetic Screening

• Genetic screening is defined as search in the
  population for persons possessing certain
  genotypes that (1) are already associated with
  disease or predisposition to disease, or (2) may
  lead to disease in their descendants.

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Principles of Screening

• Disease Characteristics, The disease should be
  serious and relatively common. There should be a
  cost/benefit justification. The natural history
  of the disease should be clearly understood.
  There should be acceptable and effective
  treatment or in the case of genetic conditions
  prenatal diagnosis should be available.
• Test Characteristics, The test should be
  acceptable, easy to perform, relatively
  inexpensive and be reliable and valid.
• System Characteristics, The resources for
  diagnosis and treatment must be accessible and a
  strategy for communicating the result efficiently
  and effectively must be in place.

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Test Validity
Tests are rarely 100 sensitive nor 100 specific.
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New born Screening

• This represents and ideal opportunity for
  presymptomatic detection and prevention of
  genetic disease.
• PKU
• Galactosemia
• sickle cell anemia
• Duchene muscular dystrophy
• Are all good examples of conditions that fulfill
  the criterion for genetic screening.

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Heterzygote Screening

• The principles of screening can be applied to
  testing a population for carriers.
• The carriers are given information about risks
  and reproductive options.
• Examples Tay Sachs disease, Cystic Fibrosis. See
  Table 13-4

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Heterozygote testing
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Presymptomatic testing

• Is the testing of individuals who may have
  inherited a disease causing gene before they
  develop symptoms.

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Methodologies used to test for genetic variants

• RFLP analysis direct and linked
• Southern blot analysis
• PCR RFLP analysis
• Allele specific oligos
• Allele specific PCR
• DNA sequencing

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Restriction enzymes
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Restriction sites in DNA
Chromosome
A
B
C
D
DNA Probe
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Southern Blot
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RFLP analysis
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Direct detection
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Sickle Cell Anemia Pedigree
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Detection of deletions
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Restriction sites in DNA
Chromosome
A
B
C
D
DNA Probe
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PCR RFLP Analysis
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Allele specific PCR
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Allele Specific Oligos
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Detection of Triplet repeats
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DNA sequence analysis for mutation detection.
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Clinical and Ethical Issues
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UNIQUENESS OF DNA TESTING

• Information may affect an entire family, rather
  than only the individual.
• Genetic discoveries may be predictive of future
  adverse events in an individual's or family
  member's health.

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UNIQUENESS OF DNA TESTING

• Genetic information and the choices of the
  present may affect future generations
• Medical genetics has a tradition of
  non-directiveness in counselling

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UNIQUENESS OF DNA TESTING

• Freedom of choice in all matters relevant to
  genetics. The woman should be an important
  decision-maker in reproductive matters

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UNIQUENESS OF DNA TESTING

• Voluntary approach is necessary in services,
  including approaches to testing and treatment
  avoidance of coercion by government, society or
  physicians
•      

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UNIQUENESS OF DNA TESTING

• Respect for human diversity and for those whose
  views are in the minority.
• Respect for people's basic intelligence,
  regardless of their knowledge.

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UNIQUENESS OF DNA TESTING

• Education about genetics for the public, medical
  and other health professionals, teachers, clergy
  and other persons who are sources of religious
  information.

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UNIQUENESS OF DNA TESTING

• Genetic screening and testing should be preceded
  by adequate information about the purpose and
  possible outcomes of the screen or test and
  potential choices to be made

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UNIQUENESS OF DNA TESTING

• Results should not be disclosed to employers,
  insurers, schools or others without the
  individual's consent, in order to avoid possible
  discrimination

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INFORMED CONSENT AND GENETIC TESTING

• The purpose of the test
• The chance that it will give a correct prediction
• The implications of the test results for the
  individual and family         

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INFORMED CONSENT AND GENETIC TESTING

• The tested person's options and alternatives
• The test's potential benefits and risks including
  social and psychological
• Social risks include discrimination by insurers
  and employers (even though this may be illegal)

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INFORMED CONSENT AND GENETIC TESTING

• Reassure families that whatever decision
  individuals and families make, their care will
  not be jeopardized

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PRESYMPTOMATIC AND SUSCEPTIBILITY TESTING

• Genetic susceptibility testing of persons with a
  family history of heart disease, cancer or other
  common diseases of possible genetic origin should
  be encouraged, provided that information from the
  test can be used effectively for prevention or
  treatment
•        

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PRESYMPTOMATIC AND SUSCEPTIBILITY TESTING

• All susceptibility testing should be voluntary,
  preceded by adequate information and based on
  informed consent.
• Presymptomatic testing should be available for
  adults at risk who want it, even in the absence
  of treatment, after proper counselling and
  informed consent.
•        

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PRESYMPTOMATIC AND SUSCEPTIBILITY TESTING

• Testing of children or adolescents should be
  carried out only if there are potential medical
  benefits to the child or adolescent

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DISCLOSURE AND CONFIDENTIALITY

• Professionals should disclose to tested
  individuals all test results relevant to their
  health or the health of a fetus.

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DISCLOSURE AND CONFIDENTIALITY

• Test results, including normal results, should be
  communicated to the tested person without undue
  delay.
• Test results not directly relevant to health,
  such as non-paternity, or the sex of the fetus in
  the absence of X-linked disorder, may be withheld

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BANKED DNA

• A blanket informed consent that would allow use
  of a sample in future projects is the most
  efficient approach.
• DNA should be stored as long as it could be of
  benefit to living or future relatives or fetuses.

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ASSISTED REPRODUCTION AND MEDICAL GENETICS

• Egg or sperm or embryo donation,or surrogacy

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ASSISTED REPRODUCTION AND MEDICAL GENETICS

• Reproductive cloning (the creation of a fetus
  whose genome is entirely derived from another
  individual) has been rejected by many
  international bodies, including WHO, has aroused
  fears in many societies, and is not in accord
  with currently accepted international ethical
  standards.
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