Lecture 19: Chromosomal disorders

Question 1

What is a karyotype and How is it done

Answer 1

A karyotype is a visual showing of chromosomes in a cell

Its done by culture the cells, arrest them in metaphase, split the cell and separate the chromosomes, straighten and then align them in order of reducing size.

Question 2

What is strengths and weaknesses of using karyotype as cygenetic method

Answer 2

Strength: Gross screening of human genetic material : numerical/ major structural changes

Weakness: small deletions, point mutations

Question 3

What is strengths and weaknesses of using karyotype as cygenetic method

Answer 3

Strength: Gross screening of human genetic material : numerical/ major structural changes
(eg diagnostic+ prognostic info for Congential disorder, Cancer)

Weakness: small deletions, point mutations

Question 4

What is strengths and weaknesses of using conventional G banding karyotype analysis as cygenetic method

Answer 4

Strength: Gross screening of human genetic material : numerical/ major structural changes
(eg diagnostic+ prognostic info for Congential disorder, Cancer)

Weakness: small deletions, point mutations

Question 5

Compare telomere and centromere

Answer 5

Centromere is the central bit between two arms and the distal end is the telomere

Question 6

Compare telomere and centromere

Answer 6

Centromere is the central bit between two arms and the distal end is the telomere

Question 7

What is aneuploidy conditions trisomy and monosomy caused by

Answer 7

Non disjunction during meiosis 1 or 2. This happens when instead of one of the pair getting segregated to each side of the cell before its splitting, both of them go to one side so the other side is missing one.

Question 8

What are the clinical features of down syndrome

Answer 8

Most common congenital chromosomal abnormality. It has clinical features of cognitive impairment, characteristic facial features, other abnormalities eg cardiac, GI, increase risk of leukaemia

Question 9

What happens when non disjunction happens post zygotically

Answer 9

Can lead to mosaicism where in mitotic division, the non disjunction that causes one set of daughter cells to be normal and the other to be a trisomy and monosomy, the monosomy line will die out but the trisomy will continue to be part of the foetal tissues with the normal cells

Question 10

What is a structural chromosomal abnormality

Answer 10

It is a break in one or more chromosomes which result in overall loss or gain of genetic material or rearrangement of genetic material.

Question 11

Are chromosomal disorders constitutional or acquired

Answer 11

both

Question 12

What are reciprocal translocations and affect of this

Answer 12

This is where two non homologous chromosomes exchange material.

Usually can result in a phenotypically normal individual if no genetic material is lost/gained.

However there is risk that resulting offspring from this individual have an unbalanced translocation, which can cause recurrent miscarriage or dysmorphic baby who is an unbalanced carrier.
Male carriers can have oligospermia

Question 13

What is Robertsonian translocation and what is the effect of this

Answer 13

In chromosomes with long q arm and short p arm or homologous chromosomes there is a translocation where the p arm of two are lost and then the two q arms fuse so they end up having 45 chromosomes. Individuals are phenotypically normal

Question 14

How does Robertson translocations cause Down syndrome

Answer 14

The gamete of the carrier can have the normal 21 chromosome as well as the translocated 14 with the 21 stuck on it, so when combined with another person’s 21 makes trisomy 21

Question 15

What are inversions,

2 types and its effect

Answer 15

An intrachromosomal structural rearrangement which involves 2 breaks and 180’ rotation of the segment which then reattaches itself.
2 types: pericentric : both arms + centromere or paracentric : one arm

Most cases are phenotypically normal.

Question 16

Compare terminal deletion and interstitial deletion of chromosome

Answer 16

Terminal: a single break at the terminal region of a chromosome causes loss of that fragment
Whereas Interstitial: two breaks in the same chromosome means the loss of the intervening fragment

Question 17

What is Fluorescent in Situ Hybridisation (FISH) used for and how is it used

Answer 17

Detecting specific DNA sequences through co denaturing and annealing target and probe DNA that has a flurochrome label so that the cytological material can be visualised under UV fluorescence

Question 18

What is the strength and weaknesses

Answer 18

Strength:
-Can be used on any tissue with intact DNA (doesn’t have to divide)

• Can detect gene amplification in cancers
• Rapid test for selected set of chromosomes

Weakness:
-Can only be used to identify things you have a known probe for

Question 19

What is Comparative Genomic Hybridisation (CGH) and its two microarray technologies

Answer 19

This compares normal and target DNA by scanning the entire genome for gain or loss of DNA.
CGH microarrays enable the simultaneous screening of 100s of DNA regions from the same person ‘spotted’ onto a microchip.
Expression microarrays use cDNA to screen the transcriptional activity of a particular gene/gene group

Question 20

Compare the types syndrome, sequence and association

Answer 20

Syndrome: groups of anomalies that consistently occur together due to underlying cause
Sequence: cascades of effects from the original cause
Association: traits coincide more often than expected by chance