Cytogenetic Tests Flashcards
Chromosomes
Carry genetic material;
Consist of DNA carried on a protein skeleton;
Localised in nuclei;
Most of the cell cycle - decondensed;
For an actively dividing cell, the cell cycle lasts…
Approx 24 hours;
Types of cell/tissue used for constitutional cytogenetics
Postnatal - blood- not active;
Prenatal:
Amniotic fluid - inactive;
Chorionic villus - actively dividing cells from placenta;
Types of cell/tissue used for malignancy cytogenetics:
Leukemia -
Lymphoma -
Other tumours -
Blood - if leukaemic cells present;
Bone marrow - actively dividing
Lymph node biopsy;
Bone marrow;
Tumour biopsy;
Bone marrow - if tumour infiltration;
3 basic shapes of human metaphase chromosomes
Metacentric - Centromere in middle
Submetacentric - centromere towards one end
Acrocentric - centromere very close to one end;
A chromosome consists of?
Centromere; Shorter arm (p arm); Longer arm (q arm); Each arm subdivided into G-bands numbered from centromere outwards;
F.I.S.H
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;
Size of X and Y
Which has more genes?
X: larger, XX has more genes than XY
X chromosome properties
Y chromosome properties
X -
153 Mb;
195 known gene loci;
Y -
50Mb;
13 known loci (4 in common with X)
What is X inactivation and dosage disequilibrium?
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;
When does X inactivation occur?
How does it occur?
Example
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;
Types of chromosome abnormality
Numerical - Trisomy Monosomy Mosaicism Polyploidy
Uniparental origin -
Uniparental disomy
Structural - Translocation; Deletion; Inversion; Duplication; Ring; Marker; Isochromosome; Fragile site; Gaps, breaks;
Down syndrome
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;
Down syndrome physical features
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;
Clinical features of Down syndrome.
Mild to moderate mental retardation;
Frequent autistic spectrum disorder;
Cardiac defects;
Increased risk of leukaemia;
As maternal age increases, Down syndrome risk …
Increases
Edwards syndrome
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;
Patau syndrome
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;
Turner syndrome.
1 in 10,000;
Short stature, webbed neck, Low posterior hairline, small nails, wide carrying angle at elbows;
Renal anomalies
Wolf Hirshhorn Syndrome
Terminal deletion - critical region - 4p16.3;
Prominent forehead, wide set eyes (hypertelorism), broad beaked nose (Greek warrior helmet features);
Prader-Willi syndrome
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;
Angelman syndrome
Maternal deletion of proximal Long arm of chromosome 15 or paternal 15 UPD; Inappropriate laughter; Convulsions; Poor coordination (ataxia); Learning difficulties;
2 disorders caused by uniparental disomy (UPD), deletion or mutation
Prayer-willi syndrome;
Angelman syndrome
Differential gene expression
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)
