Mechanisms of Chromosomal Abnormality ✅

Question 1

What is mitosis?

Answer 1

The process by which most cells replicate

Question 2

What does mitosis result in?

Answer 2

The production of 2 identical daughter cells

Question 3

What does each of the daughter cells from mitosis contain?

Answer 3

A diploid genome (46 chromosomes)

Question 4

What is meiosis?

Answer 4

The process by which gametes are formed

Question 5

What does meiosis involve?

Answer 5

2 successive cell divisions

Question 6

What do the cells produced in meiosis contain?

Answer 6

Haploid genome (23 chromosomes)

Question 7

Is cell division perfect?

Answer 7

No, errors do arise

Question 8

What are the mechanisms of chromosomal abnormality?

Answer 8

• Non-disjunction
• Anaphase lag
• Mosaicism
• Chromosome translocations
• Reciprocal chromosome translocations
• Robertsonian translocations

Question 9

Why do numerical chromosome abnormalities occur?

Answer 9

Generally because of non-disjunction during meiosis

Question 10

What is non-disjunction?

Answer 10

When two paired chromosomes (in meiosis I) or two sister chromatids (in meiosis II) fail to separate and segregate into separate cells

Question 11

What is the result of non-disjunction in meiosis?

Answer 11

The gametes will have either too many (24) or too few (22) chromosomes

Question 12

What happens following fertilisation in a gamete with too many or too few chromosomes?

Answer 12

The zygote is either trisomic or monosomic for the relevant chromosome

Question 13

Can an embryo be trisomic for every chromosome?

Answer 13

Yes

Question 14

What happens if an embryo is trisomic for every chromosome?

Answer 14

Most will spontaneously abort

Question 15

Does non-disjunction occur in men or women?

Answer 15

It can occur in either

Question 16

What do most cases of trisomy seem to take place because of, in terms of non-disjunction?

Answer 16

Non-disjunction at meiosis I in the mother

Question 17

Why do most cases of trisomy take place because of non-disjunction at meiosis I in the mother?

Answer 17

Due to this stage being very long in women - starting before birth, and ending at ovulation

Question 18

What happens to the risk of Down syndrome with maternal age?

Answer 18

Increases, obviously.

1 in 1500 for 20 year old woman
1 in 30 for 45 year old woman

Question 19

Are all aneuplodies affected by age?

Answer 19

Similar age-dependence for all aneuplodies except Turner’s syndrome

Question 20

What is an aneuploidy?

Answer 20

The presence of abnormal number of chromosomes in a cell

Question 21

By what mechanism does Turner’s syndrome occur?

Answer 21

Anaphase lag

Question 22

What happens in anaphase lag?

Answer 22

One of the sex chromosomes (X or Y) moves too slowly to the pole of the daughter cell during cell division. It therefore ends up outside the nucleus, and is broken down

Question 23

When can anaphase lag occur?

Answer 23

During meiosis, or during early mitotic divisions of the embryo

Question 24

What does chromosomal mosaicism refer to?

Answer 24

The presence of two cell lines, with differing numbers of chromosomes in each, usually one normal and one abnormal

Question 25

Give 2 examples of mosaic chromosomal disorders

Answer 25

• Mosaic Down’s syndrome (46 XX/47 XX+21)

- Mosaic Turner’s syndrome (45,X/46, XX)

Question 26

What does mosaicism usually result in?

Answer 26

Milder phenotypes

Question 27

How can mosaicism occur?

Answer 27

When the abnormal cell line arises post-zygotically

- When aneuploidy is present from conception, but some cells revert to normal karyocyte

Question 28

Give an example of how aneuploidy can be present from conception, but some cells revert to normal karyotype?

Answer 28

Losing a copy of a trisomic chromosome - called trisomy rescue

Question 29

When is a chromosomal translocation described as ‘balanced’?

Answer 29

When there is no net loss or gain of genetic material

Question 30

When is a chromosomal translocation described as unbalanced?

Answer 30

If there is deletion or duplication of genetic material

Question 31

Why are balanced translocations important to recognise?

Answer 31

They can result in transmission of an unbalanced chromosome translocation to the offspring

Question 32

Can balanced translocations cause disease?

Answer 32

Occasionally

Question 33

When can balanced translocations cause disease?

Answer 33

If a translocation breakpoint disrupts a disease gene

Question 34

When do reciprocal chromosome translocations arise?

Answer 34

When any two chromosomes swap non-homologous segments

Question 35

What might happen in a carrier of a reciprocal translocation?

Answer 35

They may potentially have offspring with trisomy of one of the translocated segments and monosomy of the other

Question 36

What are Robertsonian translocations?

Answer 36

Translocations involving the ‘acrocentric’ chromosomes

Question 37

Which chromosomes are acrocentric?

Answer 37

13
14
15
21
22
Y

Question 38

What is an acrocentric chromosome?

Answer 38

One that has it’s centromeres close to one end

Question 39

What happens in a Robertsonian translocation?

Answer 39

Inappropriate non-homologous recombination means that 2 acrocentric chromosomes join to form a single fusion chromosome with breakpoints on the short arm, just above the centromere

Question 40

Why are balanced Robertsonian translocations important to recognise?

Answer 40

Because they may cause transmission of an unbalanced chromosome complement to offspring.

Question 41

What happens if a child inherits an unbalanced Robertsonian translocation?

Answer 41

It causes trisomy or monosomy for the affected chromosome

Question 42

What do the most frequently encountered Robertsonian translocations involve?

Answer 42

Chromosome 21