Segregation

Question 1

What is the risk of malsegregation of the rob(13;14)? (Most common robertsonian)

Answer 1

<1% across both male and female.

Malsegregation of this robersonian is rarely seen.

Question 2

What is the risk of Down syndrome to a D;21 carrier?

Answer 2

Female carrier - ~10%

Male carrier - <1% as it disrupts spermatogenesis

Question 3

What is significant about a rob(13;13) or rob(21;21) carrier?

Answer 3

100% chance of either Patau syndrome or Down syndrome conceptus.

Question 4

What happens during meiosis when a balanced translocation is present?

Answer 4

A quadrivalent is formed to allow maximum pairing.

This results in a ‘pachytene cross’.

Question 5

What are the different types of segregation? What does each mean/result in?

Answer 5

Alternate: the normal and balanced homologues segregate together e.g. balanced

Adjacent-1:
1 of each centromere segregate together e.g. unbalanced

Adjacent-2:
2 of each centromere segregate together e.g. unbalanced

3:1
3 centromeres to one pole and 1 centromere to the other e.g. unbalanced

Question 6

Out of the unbalanced segregation possibility, which is more likely?

Answer 6

Will usually segregate across longest line which is usually adjacent-1.

Question 7

What does segregation analysis achieve and entail?

Answer 7

It allows us to work out the possible outcomes at meiosis for a particular translocation.
Main steps:
1. Identify the breakpoints
2. Draw pachytene cross
3. Work out what deletion/duplication products will result from the different segregation options
4. Investigate the imbalances and whether these are viable.

Question 8

Which are associated with the highest risk:

1. Large translocated segments
2. Small translocated segments

Answer 8

Small.
When the segments are small the resultant unbalanced products are more likely to be viable and therefore pose a risk of an unbalanced and thus abnormal live birth.

Question 9

If the translocated segments are short which type of segregation will produce the least imbalance?

Answer 9

Adjacent-1

Question 10

If the centric segments are short which method of segregation will result in the least imbalance?

Answer 10

Adjacent-2

Question 11

What is the most likely method of segregation if one of the derivative chromosomes is small?

Answer 11

3:1

Question 12

What does haploid autosomal length mean?

Answer 12

An old way of determining chance of viability. Gardner and Sutherland has a table which gives haploid content for each chromosome and this can be used to determine what percentage is imbalanced. However it is nw recognised that the genetic content is much more relevant and important.

Question 13

Give an example of a known syndrome associated with 3:1 segregation.

Answer 13

Emmanuel syndrome.

3:1 segregation of the recurrent t(11;22)(q23;q11.2).

Question 14

What is tertiary trisomy?

Answer 14

Results from 3:1 segregation.

2 normal chromosomes and 1 of the derivative chromosome from the translocation

Question 15

What is interchange trisomy?

Answer 15

The balanced rearrangement plus 1 of the normal chromosomes.

Question 16

What is tertiary monosomy?

Answer 16

The gamete receives just 1 of the derivative chromosomes.
The only way this could be viable is if one of the derivatives is not far off containing all of both chromosomes e.g. contains almost a whole arm of the other chromosome and very little material has gone the other way.

Question 17

What is interchange monosomy?

Answer 17

Monosomy directly caused by 3:1 segregation of a balanced translocation.