Lecture 21: Chromosomal disorders

Question 1

What is the human karyotype of chromosomes?

Answer 1

46 Chromosomes

• 22 autosomes, pairs
• 2 sex chromosomes

Arranged in order of reducing size

Question 2

What sort of cell is human karyotyping performed on?

Answer 2

Performed on any dividing cells

i.e Bone marrow, cancer, amniotic cells, chorionic villus, peripheral blood lymphocytes

Question 3

What is useful of human karyotpying?

Answer 3

Gross screen of human genetic material
- Numerical and structural changes of chromosomes

Congenital disorders - Diagnostic info
Cancer - Diagnostic and prognostic info

Question 4

What is the p arm, centromere, q arm and telomere of a chromosome?

Answer 4

P arm = Short arm
Centromere = Junction b/w long/short arm
Q arm = Long arm
Telomere = Cap found on long arm

Question 5

What sort of chromosomal abnormalities can occur?

Answer 5

Numerical or structural

Constitutional vs acquired

Question 6

What are the names given to changes in chromosome number?

Answer 6

Aneuploidy = Chromosome number that is not a multiple of the normal haploid number = 23

Monosomy, Trisomy

Question 7

What is the cause of aneuploidy?

Answer 7

Non-disjunction during meiosis 1 or 2

Question 8

How common are numerical chromosomal abnormalities?

Answer 8

• Up to 20% of pregnancies spontaneously abort
• Estimated 50% of these during first trimester are due to chromosomal abnormalities
• Most of these are numerical abnormalities

Question 9

What are the clinical conditions of aneuploidy?

Answer 9

Down Syndrome
Turners syndrome
Klinefelter syndrome

Question 10

What is the increasing risk factor for down syndrome and what is the clinical presentation?

Answer 10

Increased risk with increasing maternal age

Clinical presentation

• Cognitive impairment
• Characteristic facial features
• Others i.e Cardiac, GI, increased leukemia

Question 11

What is klinefelter syndrome?

Answer 11

47, XXY

• Poor beard growth
• Breast development
• Under-developed testes

Question 12

What is turners syndrome?

Answer 12

45, X0

• Characteristic facial features
• Web of skin, neck
• Constriction of aorta
• Poor breast development
• Under-developed ovaries

Question 13

What is somatic mosaicism?

Answer 13

• Structural or numerical
• Occurs post zygote formation
• Mitotic non-disjunction i.e theres cells with normal chromosomes and cells with aneuploidy (mosiacism)

Question 14

What are some structural chromosome abnormalities?

Answer 14

• Reciprocal translocations
• Robertsonian translocations
• Inversions
• Deletions

Constitutional or aquired

Question 15

What is a reciprocal aka balanced translocation?

Answer 15

A two way exchange of material between two non-homologous chromosomes

Balanced typically = normal phenotype as no genetic material has been lost or gained

Unbalanced is rare

Question 16

What happens to carriers of balanced translocation?

Answer 16

• Recurrent miscarriages
• Birth of dysmorphic baby who is an unbalanced carrier
• Oligiospermia

Question 17

What is a robertsonian translocation?

Answer 17

Results from fusion of two acrocentric chromosomes to form one.

Phenotypically normal individual with only 45 chromosomes

Question 18

What are two common robertsonian translocations?

Answer 18

der(13;14)

der(14;21) (unbalanced form of this is responsible for 4% of downs)

Question 19

What is an inversion?

Answer 19

An intrachromosomal structural re-arrangement, which involves two breaks on the same chromosome- the resulting chromosome segment rotates by 180deg and re-inserts itself

Question 20

Whats the consequence of inversion?

Answer 20

• Usually phenotypically normal
• 1 in 10,000
• Risk for producing unbalanced is very low
• inv(9), inv(2) and inv(Y) occur as normal pop variants

Question 21

What are the types of chromosomal deletions?

Answer 21

Terminal deletion; Single break at the terminal region of a chromosome and loss of that fragment

Interstitial deletion; Two breaks in the same chromosome and loss of the intervening fragment

Question 22

Whats an example of a chromosomal deletion?

Answer 22

Cri-du-chat syndrome

• del chromosome 15
• Severe mental retardation
• Cat-like cry at birth

Question 23

What is conventional G-banding karyotyping used for?

Answer 23

Suspected congenital disorders

Cancer/leukemia

Question 24

What is FISH used for?

Answer 24

Detection of;

• Duplication and deletions
• Translocations

Question 25

What can be used in FISH?

Answer 25

Dividing and non-dividing cells i.e any cell type