Lecture 16- Chromosomal Disorders

Question 1

Draw a chromosome. example of nomenclature

Answer 1

…..
eg) 9p34
mutation is on chromosome 9, on the p arm, at loci 34

Question 2

When is the only time you can analyse chromosomes. What do we analyse for?

Answer 2

When the cell is dividing
eg) bone marrow, cancer
allows for a ‘gross’ broad screen of genetic material.
screen for Congenital disorder or cancer

Question 3

Chromosome abnormalities can be
numerical or
accquired or

Answer 3

Chromosome abnormalities can be
numerical or structural
accquired or congenital

Question 4

Numerical chromosomal abnormalities

Answer 4

Aneuploidy = gain or loss of a whole chromosome
loss of one = monosomy
gain of one= trisomy

due to non-disjunction in meiosis
~50% of 1st trimester abortions due to chromosomal abnormalitites, most of these numerical.

Question 5

When is aneuploidy most likely to occur

Answer 5

Non-disjunction during meiosis 1 or 2 (formation of gametes)

Question 6

Example of Numerical chromosomal disorder

Answer 6

Trisomy 21 ‘Downs Syndrome’

• most common
• increase with maternal age

mental retardation, characteristic facial features,

Aneuploidy of Sex Chromosomes
Klinefelters syndrome XXY: poor beard & testes growth, breast development

Turners syndrom XO : poor breast, ovaries

Question 7

Somatic mosaicism

Answer 7

Where non-disjunction occurs post-fertilisation >mixture of normal and aneuploidy cells.

~3% downs syndrome cases.

Question 8

Types of Structural chromosomal abnormalities

Answer 8

Reciprocal Translocations

Robertsonian translocations (predispose downs syndrome)

Inversions

Deletions

Question 9

Reciprocal Translocation

Answer 9

2-way exchange of genetic material between 2 non-homologous chromosomes.

Usually ‘balanced’, no net loos/gain of genetic material > no phenotype change

Unbalanced translocation: when a parent with a balanced translocation produces a gamete with an unbalanced translocation

Question 10

How do carriers of reciprocal (balanced) translocations present

Answer 10

• recurrant miscarriages (unbalanced translocation)

- birth to a dysmorphic baby who is an unbalanced carrier

Question 11

Inversion

Answer 11

Within the same chromosome, a segment breaks, rotates 180 degrees and then reinserts itself

• usually phenotypically normal
• rare
• risk of having unbalance offspring low

Question 12

Chromosomal deletions

Answer 12

Terminal: single break @ terminal region > loss of fragment

Interstitial L two breaks in the same chromosome and loss of that fragment

Question 13

Conventional (G banding) karyotype analysis

Answer 13

To look at big picture structural/numerical issues
-analyse (dividing) cells, identify individual chromosomes

for suspected congenital disorders (downs syndrome), recurrent miscarriages etc

also for cancer (for diagnostic AND prognostic info)

Question 14

FISH is?

Answer 14

Fluorescence In Situ Hybridization
Take fluorescent labelled DNA probes specific for a gene/chromosomes we want to look at (targeted). We can do it on dividing AND non-dividing cells.
Probe denatured and then bind to specific genes (eg: HER-2 gene which is an oncogene and will be amplified in cancer)