chromosomal abnormalities

Question 1

Define karyotype

What is the human karyotype?

Answer 1

Chromosome set of an individual species in terms of number and structure of the chromosomes.
Human karyotype:
22 pairs of chromosomes
1 pair of sex chromosomes – XX or XY

Question 2

How do you prepare a karyotype?

Answer 2

1. Collect 5ml heparinised venous blood (treated with heparin to prevent coagulation
   Can use amniotic cells, CVS (Chorionic villus sampling)
2. Isolate white cells
3. Culture in presence of phytohaemagglutin- Stimulates T-lymphocyte growth/differentiation
4. After 48 hours add colchicine - Causes mitotic arrest - metaphase
5. Place in hypotonic saline
6. Place on slide
7. Fix and stain

Question 3

What do bands in gisema staining represent?

What are dark bands called and what are light bands called?

Answer 3

Regions of different compaction of chromatin
dark - heterochromatin - more compact DNA, fewer genes
light - euchromatin - more open DNA, more genes

Question 4

What are the three different types of human chromosomes?

Answer 4

Sub-metacentric - long arm and short arm
metacentric - arms are the same length
Acrocentric - short arm replaced by non coding satellites

Question 5

What are the 5 common structures, identified by the G-Banded architecture of a chromosome?

Answer 5

Telomere on either end of the chromosome
p-arm
q-arm
G-dark and G-light bands
Centromere

Question 6

Why are karyotypes performed more in Prophase rather than Metaphase?

Answer 6

Because the chromosomes are less compact and therefore you get more detail from the karyotype

Question 7

What is aneuploidy caused by?

Answer 7

Results in uneven number of chromosomes in daughter cells -results in either an extra chromosome (trisomy) or missing chromosome (monosomy)

Question 8

What is aneuploidy?

Answer 8

Numerical chromosomal abnormailty - aneuploidy- loss or gain of chromosomes

Question 9

What is the most common form of chromosomal aneuploidy?

Why is it more tolerated than other forms of aneuploidy?

Answer 9

Sex chromosome aneuploidy

more tolerated as
- you get inactivation of excess X chromosomes, only one is active
- Y chromosomes have low gene content so an extra y will not greatly impact phenotype
however both X and Y have some pseudo-autosomal regions which will be active and cause some symptoms

Question 10

What is caused by trisomy 21?

Answer 10

Downs syndrome - 85-90% due to maternal disjunction

Question 11

How does maternal non-disjunction change with age and why?

Answer 11

Maternal non-disjunction increases with age as
Proteins become more disfunction with age
Progressive degradation of factors holding homologous chromatids together
This leads to the premature separation of homologs and of chromosomes into separated sister chromatids.

Question 12

What is turners syndrome caused by?

What is kleinfelders diseases caused by?

Answer 12

1. X monosomy

2. XXY chromosome

Question 13

Why is there a maternal age effect on chromosomal abnormalities?

Answer 13

Vulnerability of oogenesis

• oocyte paused in utero in prophase till puberty
• secondary ooctye paused in metaphase II until fertilised

as the mother ages the oocytes have been arrested in metaphase for 45 years which can cause problems
Degradation of factors that hold the chromatids together

Question 14

How do paternal genes affect risk of chromosomal abnormalities?

Answer 14

primary spermatocytes undergo 23 mitotic divisions per year and accumulate mutations

smoking is a risk factor

single point mutations in genes FGFR2, FGFR3 and RET which increase sperm viability can lead to certain conditions including:

• apert syndrome
• Crouzon syndrome
• pfeiffer syndrome

Question 15

When can chromosomal abnormalities occur?

Answer 15

During crossing over

During DNA replication

Question 16

How does crossing over occur and why?

Answer 16

occurs in prophase I
pairs of chromosomes align
Chiasma forms and crossing over occurs
1-3 times per chromosome per meiosis

Increases genetic diversity

Question 17

What 5 changes can occur in the banding sequence of a chromosome to cause an abnormality?

Answer 17

Deletion 
Duplication 
Inversion 
Insertion - unequal exchange 
Translocation - the  junction of exchange causes for an abnormal protein

Question 18

What is robertsonian translocation?

Answer 18

Robertsonian translocation involves acrocentric chromosomes.
Breakage at the centromere, satellites are lost and the two q arms fuse.
Most people are unaffected as satellites don’t code for anything so no genetic information is lost but may affect offspring as they inherit a chromosome with double the amount of genetic information

Question 19

What is mosaicism and how does it occur?

Answer 19

Presence of two or more populations of cells with different genotypes - an individual will have two different sets of DNA

occurs due to

• mitotic non-disjunction during embryonic development
• Loss of extra chromosome in early development

mutant cell in zygotes mitosis carries on dividing and the normal zygote also divides

Question 20

What is a structural abnormality?

Answer 20

Number of chromosomes stays the same but the structure of the chromosome is altered

Question 21

Explain how Unequal Crossing Over occurs?

Answer 21

Chromosomes do not align correctly at centromeres

Unequal lengths of chromatids are exchanged

Leading to deletion of genes in one chromosome

And duplication of genes in the other chromosome

Question 22

What are the 2 types of inversion in single chromosome abnormalities?

Answer 22

Paracentric inversion - Breaks in chromosome occur in middle of chromosome arm & that section of chromosome is inverted, creating reinvented piece of DNA

Pericentric inversion - Breaks occur around centromere & that section of chromosome is inverted, creating reinvented piece of DNA

Question 23

What is the translocation occuring in chronic myeloid leukaemia?

Answer 23

Fusion of part of ABL 1 gene from chromosome 9 with part of BCR gene from chromosome 22, creating abnormal fusion gene called BCR-ABL1

This translocation is written as t(9;22)(q34;q11)

Question 24

What is meant by a de-novo chromosomal abnormality?

Answer 24

When the abnormality was not inherited from the parent of the patient and so it is new to the individual

Question 25

What causes William’s syndrome and what are the symptoms of William’s syndrome?

Answer 25

7q11.23 deletion

long philtrum 
slightly upturned nose 
lack social anxiety 
arched eyebrows
Supravalvular aortic stenosis

Question 26

What is one of the chromosomal features of William’s syndrome?

Answer 26

Lack of elastin on affected chromosome

Question 27

Which chromosomes are generally acrocentric in humans?

Question 28

Which chromosomes are generally acrocentric in humans?

Answer 28

13

14

15

21

22