Genetic Testing

Question 1

Less restrictive definitions

Answer 1

Include non-DNA teseting.
Analyzing an individual’s genetic material to determine predisposition to a particular health condition or to confirm a diagnosis of genetic disease.
Examining a sample or blood or other fluid/tissue for biochemical or chromosomal or genetic biomarkers to indicate genetic disease.
You can test amino acids, organic acids, enzyme activity, x-rays etc.

Question 2

Chromosomal analysis

Answer 2

Looking at chromosome number or structure (deletion, insertion, rearrangement).
Good for testing in pregnant women.
What can you not see? Single gene deletions, point mutations, small deletions/duplications/insertions. Methylation defects. Tri-nucleotide repeat issues. NO SMALL STUFF.

Question 3

FISH

Answer 3

Can see deletions, translocations, and abnormalities of copy number.
Its resolution goes beyond chromosomal analysis.

For recognized issues. Because you have to design a specific probe. Not always going to see duplications, deletions, or point mutations.

Examples of things you can see? Cri-du-chat, DiGeorge, Prader-Willi, Angelman

Question 4

Microarray analysis

Answer 4

Also called comparative genomic hybridization (CGH).

You are seeing if genes are turned on or off (RNA expression). Activity of gene.
VERY IMPORTANT. Because they can see deletions and duplications.
You can only see unbalanced rearrangements. And aneuploidies.
Can’t see really small deletions/duplications, nucleotide mutations, or balanced rearrangements.

Question 5

DNA sequencing

Answer 5

You need to know something about the diagnosis, the gene, and know that the mutation is detectable.
So it’s great for a known disease gene.

Also realize that even though it’s very specific does not mean it’s going to be 100% sensitive. You won’t see BIG deletions/insertions, rearrangements, and most chromosome abnormalities.

Question 6

Informative vs. non-informative

Answer 6

Informative is probably true positive or true negative.

Question 7

Example of allelic heterogeneity?

Answer 7

Cystic fibrosis. Many diff mutations. But is genetically homogeneous.

Question 8

Example of genetic heterogeneity

Answer 8

Hypertrophic myopathy. At least 10 diff genes (also shows allelic heterogeneity).
This allelic/genetic heterogeneity is an issue with genetic testing because it can’t account for it.