Genetic Testing

Question 1

1. ) Chromosomal analysis:
   - Used to?
   - Pros?
   - Cons?
   - Ex?
2. ) FISH:
   - Used to? What phase?
   - Pros?
   - Cons?
   - Probe types? (3)

Answer 1

• Chrom # or major structural changes
• Aneuplodies, 3-5mb del/dup/reloc.
• Not good for single gene, point, methylations
• WAGR
• Del, trans, copy #, interphase
• Microdeletions, rearrange, copy #’s, balanced rearangements
• Must know where to look, point
  1. ) Centromere = Enumeration
  2. ) Locus specific = deletion (P53)
  3. ) Fusion = translocations (leukemias)

Question 2

3. ) CMA: Looks for?
   - Pros?
   - Cons?
4. ) DNA Sequencing: Tool used?
   - Pros?
   - Cons?

Answer 2

• Gains or losses, and limited mosaicism
• Unbalanced translocations, CNV’s (but not always clinically relevant
• Balanced rearrangements, point
• Sangers
• Mutations in known genes, new mutations, polymorphic variations
• Doesn’t test promoters or introns, not great with large deletions or rearrangements

Question 3

• Genetic testing doesn’t need?
• Informative test?
• Non-informative test?
• Allelic heterogeneity? Ex?
• Genetic heterogeneity? Ex?
• These factors play role in?
• 3 interesting examples?

Answer 3

• DNA
• Definitely diagnoses or rule out disease
• Not definitive
• Multiple mutations in particular gene can cause disease; CF
• Multiple genes associated with phenotype; hypertrophic cardiomyopathy
• Informative or not
• Sickle cell = genetic/allelic homogeneity
• CF = genetic homo; allelic hetero
• Alzheimers is homo for both

Question 4

• Two most common leukemia translocations:
• Name? Location? Treatment?
• Genetic testing algorithm?

Answer 4

1. ) CML (t9:22) = Philadelphia chromosomes; gleevac, tyr kinase inhibitors
2. ) AML/PML/APL (t15:17); retinoic acid, arsenic trioxide

CMA –> CNV’s then use FISH –> FISH Family –> Lit Search if not in family –> check for balance translocation