Cytogenetic Tests

Question 1

Chromosomes

Answer 1

Carry genetic material;
Consist of DNA carried on a protein skeleton;
Localised in nuclei;
Most of the cell cycle - decondensed;

Question 2

For an actively dividing cell, the cell cycle lasts…

Answer 2

Approx 24 hours;

Question 3

Types of cell/tissue used for constitutional cytogenetics

Answer 3

Postnatal - blood- not active;
Prenatal:
Amniotic fluid - inactive;
Chorionic villus - actively dividing cells from placenta;

Question 4

Types of cell/tissue used for malignancy cytogenetics:
Leukemia -
Lymphoma -
Other tumours -

Answer 4

Blood - if leukaemic cells present;
Bone marrow - actively dividing

Lymph node biopsy;
Bone marrow;

Tumour biopsy;
Bone marrow - if tumour infiltration;

Question 5

3 basic shapes of human metaphase chromosomes

Answer 5

Metacentric - Centromere in middle
Submetacentric - centromere towards one end
Acrocentric - centromere very close to one end;

Question 6

A chromosome consists of?

Answer 6

Centromere;
Shorter arm (p arm);
Longer arm (q arm);
Each arm subdivided into G-bands numbered from centromere outwards;

Question 7

F.I.S.H

Answer 7

Flurorescence in Situ hybridisation;
Segment of single stranded DNA is labelled with a fluorescent tag;
It is then hybridised to target DNA (chromosomes) attached to a slide;
It hybridises with matching DNA sequence;

Question 8

Size of X and Y

Which has more genes?

Answer 8

X: larger, XX has more genes than XY

Question 9

X chromosome properties

Y chromosome properties

Answer 9

X -
153 Mb;
195 known gene loci;

Y -
50Mb;
13 known loci (4 in common with X)

Question 10

What is X inactivation and dosage disequilibrium?

Answer 10

Females carry 2 copies of genes on X chromosome; males only have one;
If both copes of X chromosome transcribed - females would have twice the dosage of gene products as men;
X inactivation balances this as it switches off one copy of the gene in X in females;

Question 11

When does X inactivation occur?
How does it occur?
Example

Answer 11

Occurs at the 5,000 cell stage;
2 weeks post fert;
Occurs randomly but once established all Daughter cells retain the same pattern of inactivation as their progenitor;
Causes the patchy coat of Tortoiseshell cats - a coat colour allele expressed only from the active X;

Question 12

Types of chromosome abnormality

Answer 12

Numerical - 
Trisomy
Monosomy 
Mosaicism
Polyploidy

Uniparental origin -
Uniparental disomy

Structural -
Translocation;
Deletion;
Inversion;
Duplication;
Ring;
Marker;
Isochromosome;
Fragile site;
Gaps, breaks;

Question 13

Down syndrome

Answer 13

Most common cause of mental retardation;
1/650 births;
Trisomy 21 -94% - Majority arise through non-disjunction at maternal meiotic 1st division;
Unbalanced Robertsonian translocation;
Mosaic - 2% - post-zygotic,mitotic non-disjunction event;

Question 14

Down syndrome physical features

Answer 14

Flat facial profile - flattened nose;
Eyes (palpebral fissures) slant upwards;
Small ears;
Flat back of the head (brachycephaly);
Protruding tongue;
Bilateral single palmar crease;
Shorter than average with poor muscle tone;

Question 15

Clinical features of Down syndrome.

Answer 15

Mild to moderate mental retardation;
Frequent autistic spectrum disorder;
Cardiac defects;
Increased risk of leukaemia;

Question 16

As maternal age increases, Down syndrome risk …

Answer 16

Increases

Question 17

Edwards syndrome

Answer 17

Birth - 3/10,000;
Growth retardation, prominent occiput (back of head);
Small mouth, clenched hands, overlapping fingers, prominent heels (rocker bottom feet);
Congenital heart disease, renal anomalies;
50% die by 2 months of age;
3 copies of chromosome 18;

Question 18

Patau syndrome

Answer 18

Birth: 2 in 10,000;
Scalp defects, hypotelorism (narrow distance between eyes), polydactyly (extra digits), cleft lip and palate;
Holoprosensephaly, congenital heart disease, renal abnormalities;
69% die by 6 months;
3 copies of chromosome 13;

Question 19

Turner syndrome.

Answer 19

1 in 10,000;
Short stature, webbed neck, Low posterior hairline, small nails, wide carrying angle at elbows;
Renal anomalies

Question 20

Wolf Hirshhorn Syndrome

Answer 20

Terminal deletion - critical region - 4p16.3;

Prominent forehead, wide set eyes (hypertelorism), broad beaked nose (Greek warrior helmet features);

Question 21

Prader-Willi syndrome

Answer 21

Paternal deletion of proximal Long arm of chromosome 15 or maternal chromosome 15 UPD;
Extremely floppy in early infancy (hypotonia);
Develop marked obesity through over-eating;
Mild to moderate learning difficulties;

Question 22

Angelman syndrome

Answer 22

Maternal deletion of proximal Long arm of chromosome 15 or paternal 15 UPD;
Inappropriate laughter;
Convulsions;
Poor coordination (ataxia);
Learning difficulties;

Question 23

2 disorders caused by uniparental disomy (UPD), deletion or mutation

Answer 23

Prayer-willi syndrome;

Angelman syndrome

Question 24

Differential gene expression

Answer 24

Some genes are only expressed on the chromosome that is inherited from either the Father or Mother;
These genes are controlled by methylation (imprinted);
Can cause disease if expressed gene is absent (due to chromosomal deletion or uniparental disomy)

Question 25

Some examples of cytogenetic referral

Answer 25

Recurrent miscarriage;
Learning difficulties/ congenital abnormalities;
Infertility;
Prenatal diagnosis;