Balanced structural chromosomal abnormalities

Question 1

What is important in ensuring that chromosome segregation happens correctly in meiosis (one round of DNA replication, two rounds for chromosome segregation).

Answer 1

The number of crossovers and positionof crossovers

Question 2

What can structural rearrangements be?

Answer 2

Begnin (carrier of balanced rearrangement)

Question 3

If you are born as a carrier of balance rearrgangement. Why might might you have recurrent misscarriage or inability to establish pregnancy. or if you have child they are at risk of genetic disorder.

Answer 3

Rearrangements in the genome when they are segregated through meiosis, form abnormal structures in that process of cell division. Those abnormal structures disturb the normal number of crossovers and position of crossovers between homologous regions of the genome.

Fundamental principle: number of and position of crossovers ensure that you segregate chromosomes correctly.

Question 4

What are the types of balanced gross structural rearrangements?

Question 5

Types of inversion

Answer 5

Preicentric: Breakpoints located either side of the centromere.

Paracentric: Breakpoints lacoted in same arm.

Question 6

Pericentric inversion formed?

Answer 6

DNA is damaged.
Robust DNA repair mechanisms which repair the damage.
The damage mush of the time is repaired faithfully however can go wrong.
Goes wrong due to repair apparatus wrapping around site of damage has grabbed hold of illegitimade piece of DNA.
Results in inversion.

Question 7

Whats illegitimate recombination

Answer 7

used to desribe repair events where the template is loacted on a non-equivalent genomic position.

For example, if a site of damage in the P arm of a chromosome is repaired using homologous template sequences in the q arm this would be an example of illegitimate repair.

Question 8

How would a repair lead to an inversion?

Answer 8

If the break was repaired via crossover formation - this would lead to an inversion – which is the first type of structural rearrangement that we’ll discuss.

Question 9

How would a break be correctly repaired in meiosis 1 and mitosis

Answer 9

Meiosis 1 - Grab hold of piece of homologous sequence in the homolog in same position.

Mitosis: grab hold of homologous sequence in sister chromatid.

Question 10

What are the features of pericentric inversion?

Answer 10

Chnage in banding structure.
CHange in position of centromere.
This is mainly due to the assymmetrical positioning of inversion ‘breakage points’ with respect to the centromere.

Question 11

Why are homologous sequences away from one another. which chromosomes are kept away from one another

Answer 11

so genome can be used and replicated and segregated correctly without jumbling it up.

Chromosome 9 and 22 kept away from one another. (listen to again - ~10:20)

Question 12

How do inversions affect Oogenesis and spermatogenesis

Answer 12

Does not affect Oogenesis however affects Spermatogenesis.

Question 13

What do inversons requires?

Answer 13

Two breakpoints in the same chromosome

Question 14

Feature of paracentric inversion

Answer 14

Does not alter the morphology of the chromosome.
Alters the banding structure.

Question 15

What do paracentric inversions form?

Answer 15

Form looped structures.
Which can segregate normally.
However, if a crossover forms within the region on inversion then things start to go wrong.

Question 16

WHat happens to piecce of DNA that isnt connected to a centromere?

Answer 16

It is lost

Question 17

What do inversions increase the risk of?

Answer 17

Unbalanced gamete formation.

Question 18

WHat does the risk associated with how many unbalanced gametes you would form is carrier of a inversion depend on?

Answer 18

if inversion is small - unlikely crossover would land within the inversion.

Therefore size dictates risk of unbalanced gametes being produced.

Question 19

A crossover within inverted fragment results in?

Answer 19

Production of unbalanced gametes

Question 20

What do insertions require?

Answer 20

Two breakpoints in the same chromosome and one in another.

Question 21

Why are insertions rare?

Answer 21

There are three regions of genome all needing to interact with eachother at the same time. (whereas transloations only require 2)

Question 22

WHat do translocations require?

Answer 22

Require one break in each chromosome.
Common, 2-4 in every 1000 live births.

Question 23

WHat do translocation rearrangements form?

Answer 23

Abnormal structures in meisos.
which is disturb normal number and position of crossovers between homologous regions of genome.
Results in abnormal gametes being formed.

Question 24

WHat stage do chromosomes start to pair up?

Answer 24

Prophase

Question 25

Whats a pachytene cross and why do they form?

Answer 25

Crossing over of genetic material occurs between non-sister chromatids

Most efficent way to ensure allelic regions of the genome between homologous chromosomes can pair up.

They need to pair up so they can form crossovers, so you can generate tension across miotic spindle and that enables cell to faithfully segregate chromosomes.

Question 26

Describe alternate segregation, (separate pachytene cross by alternate segregation).

Answer 26

Have alternate centromeres (one goes up and one goes down).

At anaphase of meiosis I, alternate centromeres are segregated to the same pole of the cell.

Sister chromatids are then segregated at anaphase in meiosis II into 4 gametes

Question 27

What does alternate segregation produce?

Answer 27

4 viable gametes, each with full and balanced haploid complement of chromosomes.

Question 28

What happens if there is alternate segregation of sister chromatids with balance alteration?

Answer 28

Will generaet gametes with a full and normal complement of DNA with regards to chromosome 11 and 14 (example in slides) but every gamete will be a carrier of balanced rearrangement.

Question 29

Whats another way (other than alternative) to segregate chromosomes?

Answer 29

M1 adjacent segregation.

Question 30

Describe adjascent 1 segregation.

Answer 30

Adjascent centromere are cosegregated.

Question 31

Whats the third way to segregate chromosomes?

Answer 31

M1 Adjascent II segregation.
Outcome is that unbalanced gametes are generated.
imbalances so large that foetus would spontenously abort.

Question 32

What is 3:1 mal segregation errors more likely?

Answer 32

When there is an additional long axis for the cell to choose from.

Question 33

If 3:1 mal segregation error occurs and pregnancy established, what genetic disorder would the child have?

Answer 33

Emanuel syndrome - read the further reading.