Chromosome Abnormalities

Question 1

Light bands vs dark bands of chromosomes (when do they replicate, is chromatin condensed, what are they rich in)

Answer 1

• Light replicate early in S phase, dark late
• Light have less condensed chromatin, dark have condensed
• Light are gene and GC rich, dark AT rich)

Question 2

What is the DNA above and below the centromere on a chromosome called?

Answer 2

• Above = short arm (p)
• Below = long arm (q)

Question 3

3 methods of examining chromosomes

Answer 3

• Karyotype
• Fluorescent in situ hybridisation (FISH)
• Array CGH

Question 4

How does fluorescent in situ hybridisation work and what does it show?

Answer 4

• Fluorescent probes hybridise to specific areas of interest
• Shows if a patient has extra or missing bits

Question 5

How does array CGH work?

Answer 5

• You have green test DNA and red reference DNA
• A DNA microarray is prepared with probes representing regions of interest
• The two DNAs are allowed to compete for the probes
• If the test is the same as reference, it will appear yellow, if extra in test then it will be green and if missing in test then it will be red

Question 6

2 classifications of chromosome abnormality

Answer 6

• Abnormalities of number
• Abnormalities of structure

Question 7

What is the general format of writing a karyotype?

Answer 7

Total number of chromosomes, sex chromosomes, abnormalities (eg. male with trisomy 21 = 47,XY,+21)

Question 8

Types of abnormality of chromosome number

Answer 8

• Trisomy (3 chromosomes of one number)
• Monosomy (1 chromosome of one number)
• Triploidy (3 sets of chromosomes (ie. 69)
• Tetraploidy (4 sets of chromosomes (ie. 92)

Question 9

Most frequent abnormalities of chromosome number in liveborn

Answer 9

• Autosomes
  > Down syndrome (47,X_,+21)
  > Edwards syndrome (47,X_,+18)
  > Patau syndrome (47,X_,+13)
• Sex chromosomes
  > Turner syndrome (45,X)
  > Klinefelter syndrome (47,XXY)
• All chromosomes
  > Triploidy

Question 10

Proportions of different genetic causes of Down syndrome

Answer 10

• Non-disjunction in meiosis II leading to 2 copies in one gamete = 95%
• Robertsonian translocation = 4%
• Mosaicism due to non-disjunction after fertilisation = 1%

Question 11

Symptoms of Edwards syndrome

Answer 11

Multiple malformations especially of the heart and kidneys

Question 12

Symptoms of Klinefelter syndrome

Answer 12

• Infertility
• Poorly developed secondary sexual characteristics
• Tall

Question 13

Symptoms of Turner syndrome

Answer 13

• Short stature
• Primary gonadal failure

Question 14

Abnormalities of chromosome structure

Answer 14

• Translocations (Robertsonian and reciprocal)
• Deletion
• Duplication
• Inversion
• Ring chromosome
• Marker chromosome
• Complex rearrangements

Question 15

How does a Robertsonian translocation work?

Answer 15

• 2 acrocentric chromosomes break at or close to the centromere
• Long arms fuse
• Short arms are lost

Question 16

2 types of Robertsonian translocation

Answer 16

• Balanced
• Unbalanced

Question 17

What is a balanced Robertsonian translocation?

Answer 17

All chromosome material is present, just in a different location (eg. person has 1 chromosome 14, 1 chromosome 21 and 1 chromosome containing both)

Question 18

What is an unbalanced Robertsonian translocation?

Answer 18

Offspring inherit both normal chromosomes of one pair, but get a third copy of that pair attached to a different pair

Question 19

What is an acrocentric chromosome and which are acrocentric?

Answer 19

• Chromosomes where the centromere is not central and instead very close to one end
• 13, 14, 15, 21, 22

Question 20

How does a reciprocal translocation work?

Answer 20

• 2 non-homologous chromosomes break
• The fragments are exchanged

Question 21

What can reciprocal translocations cause in offspring and how?

Answer 21

• Partial trisomy/monosomy
• They receive 1 normal chromosome from one parent and 1 chromosome with a bit missing/extra from the other

Question 22

How do large chromosome deletions/duplications occur?

Answer 22

Unequal crossing over in meiosis following a mispairing at sites of repeated sequences