Lecture 24-Molecular Cytogenetics

Question 1

How did FISH improve clinical cytogenetic diagnoses?

Answer 1

• it allowed cytogenetic diagnoses to be made irregardless of whether or not the cell is in metaphase
• this is good because looking at cells in interphase can allow you to look at both the morphologic changes as well as genetic changes in the cell

Question 2

CGH is important for measuring what?

Answer 2

chromosomal gains, losses and aneuploidy

Question 3

What’s a constitutional abnormality?

Answer 3

• a chromosomal abnormality resulting in a birth defect

Question 4

What’s an acquired abnormality?

Answer 4

• a chromosomal abnormality usually associated with cancer

Question 5

FISH can detect _______ syndromes to up to what resolution (i.e., how many bps)?

Answer 5

• microdeletion

- ~1 Mb–higher resolution than G banding

Question 6

Name the cytogenetic diagnostic techniques from greatest to smallest resolution.

Answer 6

• CGH: individual bases

- FISH: ~1 Mb resolution

Question 7

Subtelomeres

Answer 7

• have the highest concentration of genes out of all chromosome regions so deletions/duplications here have significant phenotypic effects.

Question 8

Telomeric rearrangements cannot be seen by _______. Why?

Answer 8

• G-banding

- all telomeres have similar G-band light regions

Question 9

Subtelomeric rearrangements not visible by G-banding have been found in 4-9% of individuals who________

Answer 9

have idiopathic mental retardation.

Question 10

Can FISH give info about fixed cells?

Answer 10

yes

Question 11

Because FISH doesn’t require dividing cells (like G banding) it can be used to detect chromosomal abnormalities in people who _______ (2).

Answer 11

• are on chemotherapy

- post bone marrow transplant

Question 12

In interphase FISH analyses the probes target _______ of what chromosomes?

Answer 12

• centromeres

- 13, 18, 21, X, Y to look for trisomies

Question 13

What other uses are there for interphase FISH analysis?

Answer 13

• when being used on uncultured amniotic cells and time is an issue
• fixed cells (tumor evaluation)
• low mitotic index samples (patients on chemo, post bm transplant)

Question 14

Chromosome analysis is used in cancer to look for _______.

Answer 14

• recurrent chromosome abnormalities (abnormal clone)

Question 15

What can be a prognostic indicator of leukemia? What would indicate a poor prognosis?

Answer 15

• CNVs

- acquisition of additional karyotypic abnormalities after diagnosis signaling evolution

Question 16

What is a “masked” translocation in CML?

Answer 16

• when its a microscopic translocation. This is seen in 5% of CML patients

Question 17

Can you have CML without some combination of bcr and abl?

Answer 17

• no

Question 18

CML has what translocation?

Answer 18

9:22
NOTE: t(9:22)(q34;q11.2)

Question 19

What is an inhibitor of bcr-abl?

Answer 19

• gleevac: an inhibitor of the abl tyr kinase

Question 20

Which has higher resolution FISH or whole chromosome painting?

Answer 20

• FISH

Question 21

When do you use whole chromosome painting?

Answer 21

• when theres a marker chromosome and you don’t know which chromosome its from so you don’t know what sequences to probe for

Question 22

What is a marker chromosome?

Answer 22

• a small chunk of chromosome that has unknown origin usually, but you can use chromosome painting to figure it out

Question 23

What population are chromosome markers more common in?

Answer 23

• 10X more common in “mentally subnormal”

Question 24

If a marker is not inherited and is an autosomal ring ______.

Answer 24

• there is a 30% chance of abnormalities

Question 25

Give 2 examples of cancer genes that are amplified in turmors and thus, discovery of these can impact treatment.

Answer 25

• HER2/NEU: breast cancer

- MYCN: neuroblastoma