Lecture 13 - Special Topic - Medical Cytogenetics

Question 1

What are the different types of chromosomal abnormality?

L13 S6

Answer 1

Constitutional:

• chromosome abnormality is present in a gamete from parents and results in all cells in the offspring having the abnormality (homogenous abnormality)
• chromosome abnormality occurs early in the development of zygote and is present in some but not all cells of the offspring (mosaic abnormality)

Acquired:
-chromosome abnormality occurs in developed offspring and is only present in the tissue it occurred in (cancer)

Question 2

What are reasons for parental cytogenetic screening?

L13 S7

Answer 2

• abnormal prenatal screening
• advanced maternal age
• abnormal US
• family history

Question 3

What are reasons for postnatal cytogenetic testing?

L13 S8

Answer 3

• family history
• multiple miscarriages
• birth defects
• developmental delay/abnormal growth
• confirmation of diagnosis
• genital ambiguity

Question 4

What advancement in cytogenetics occurred with the use of hypotonic solutions?

L13 S16-17

Answer 4

Metaphase chromosomes would spread out allowing for proper counting and observation.

Question 5

What advancements occurred with the discovery of Giemsa-banding (G-banding)?

What are some limitations/disadvantages of it?

L13 S22-23

Answer 5

It allowed for detection of structural rearrangements, large deletions, or large duplications.

Limitations/disadvantages:

• LOTS of training
• can’t detect smaller changes
• can miss low level or tissue specific abnormalities
• can’t show epigenetic changes
• REQUIRES ACTIVELY DIVIDING CELLS

Question 6

What is FISH and what advancements occurred because of it?

What are the advantages?

What are some limitations/disadvantages of it?

L13 S26

Answer 6

Fluorescent In Situ Hybridization

Fluorescent stained DNA fragments that are complimentary with human DNA that can show if there are changes.

Advantages:

• does not require dividing cells
• rapid and large quantities
• can detect smaller changes

Limitations/disadvantages:

• targeted test that requires suspicion of specific diagnosis
• only 2-3 probes per hybridization
• can’t detect epigenetic

Question 7

What are DNA microarrays?

What are the advantages?

What are some limitations/disadvantages of it?

L13 S29

Answer 7

Labeled pt DNA and control DNA compete to bind to sites in microarray showing changes in copy number variant (gain or loss of material)

Advantages:

• can detect deletion, duplications, and amplifications (even the degree to which they occur)
• requires small amounts of DNA
• does not require suspicion of specific disease
• can detect smaller changes

Limitations/disadvantages:

• balanced chromosomal rearrangements are not detected
• only looks at regions array is designed for
• mosaicism can be masked by normal cells at lower levels
• most abnormalities are nonspecific