Chromosomes and Chromosomal Abnormalities

Question 1

Explain basic chromosomal organisation

Answer 1

Telomere (end portions)
Short arm (p)
Centromere (spindle connects here in mitosis)
Long arm (q)
Telomere (end portions)

Question 2

How is a chromosome recognised ?

Answer 2

Banding pattern with specific stains
Length
Position of centromere

Question 3

Acrocentric chromosomes

Answer 3

• the short arm doesn’t really matter
• mainly observe long arm

You see:

• centromere
• long arm

Question 4

State some acrocentric chromosomes

Answer 4

Chromsomes:

-13
-14
-15
-21
-22

Question 5

Chromosome changes that cause disease

Answer 5

Balanced chromosome rearrangement
Unbalanced chromosome rearrangement

Question 6

Balanced chromosome rearrangement

Answer 6

All chromosome material is present
- physical change in location effectively

Question 7

Unbalanced chromosome rearrangement

Answer 7

Extra or missing chromosomal material.

Usually 1 or 3 copies of some of the genome.

Question 8

Aneuploidy

Answer 8

Whole extra or missing chromosome

Question 9

Translocation

Answer 9

Rearrangement of chromosomes

Question 10

State some chromosome changes

Answer 10

Insertions
Deletions
Duplications
Inversions

Question 11

Aneuploidy and Non-disjunction in meiosis

Answer 11

Genome doesn’t develop correctly
Occurs prior to fertilisation.

Question 12

Non-disjunction

Answer 12

When chromosomes fail to separate normally, resulting in a gain or loss of chromosomes.

Question 13

Down Syndrome

Answer 13

47 XY + 21

Trisomy 21 (additional chromosome 21)

Question 14

Edward Syndrome

Answer 14

47 XY + 18

Trisomy 18 (additional chromosome 18)

Question 15

Patau Syndrome

Answer 15

47 XY + 13

Trisomy 13 (additional chromosome 13)
- associated with cleft palate

Question 16

How are trisomy diagnoses picked up ?

Answer 16

Rapid prenatal diagnosis
- Interphase chromosome counting using FISH (fluorescence in situ hybridisation)

• Array CGH

Question 17

FISH

Answer 17

Fluorescence In Situ Hybridisation

Question 18

45 X

Answer 18

Turner Syndrome

Lack of one sex chromosome
Females with only one X chromosome

Question 18

Array CGH

Answer 18

Mix 2 types of genomic DNA together.

Label one with green and one with red.

If equal numbers of both –> yellow signal

If non-equal numbers –> you would see the predominant colour come through.

Use computer software and a data plot.

Anything above the zero reference = gain of chromosomal info

Below zero reference = loss of chromosomal info

Question 19

Why is X chromosome aneuploidy better tolerated ?

Answer 19

Due to X chromosome inactivation

Question 20

47 XXY

Answer 20

Klinefelter syndrome

Question 21

47 XXX

Answer 21

Triple X

Question 22

State the 2 major chromosome mutations

Answer 22

1. Chromosomal Insertion
2. Chromosomal Translocation

Question 23

Robertsonian Translocation

Answer 23

2 Acrocentric chromosomes (only Q arm) stuck end to end.

End-end fusions around the centromeres.

Question 24

Results of Robertsonian translocation

Answer 24

Increased risk of trisomy in a pregnancy

Question 25

Trisomy 14

Answer 25

Miscarriage

Question 26

Reciprocal translocation

Answer 26

Exchange of information between the different chromosome pairs. (acentric and centric fragments)

Question 27

Results of Reciprocal translocations

Answer 27

Reproductive risks - For most translocations, ~50% of conceptions will have either normal chromosomes or the balanced translocations Unbalanced products result in - miscarriage (large segments) - dysmorphic delayed child (small segments)

Question 28

What do unbalanced products result in ?

Answer 28

- miscarriage (large segments) - dysmorphic delayed child (small segments)

Question 29

Clinical effects of chromosomal abnormalities

Answer 29

Cancer

Question 30

Cancer - Philadelphia chromosome

Answer 30

Break between 2 segments Chromosome 9 and chromosome 22 Balanced translocation effect. Movement of ABL fuses with BCR. ALTERED CHROMOSOME 22

Question 31

Philadelphia chromsome

Answer 31

Chromsome 22

Question 32

Single Chromosome Mutations

Answer 32

Deletion Duplication Inversion

Question 32

Philadelphia chromosome FISH

Answer 32

bar-abl is a chimeric oncogene 95% of CML patients have Ph Ch

Question 33

Chromosomal Deletion example

Answer 33

X-linked Ichthyosis

Question 34

Chromosomal Duplication example

Answer 34

Charcot Marie Tooth disease

Question 35

Charcot Marie Tooth disease

Answer 35

Damage to myelin sheath in peripheral nerves - progressive loss of muscle tissue and touch sensation Mutations in 39 genes can cause CMT Commonest form - CMT1A 70-80% cases have a large duplication of 17p11.2

Question 36

Chromosomal Inversion

Answer 36

Rare Most common inversion (2%) - inversion on chromosome 9