Cytogenetic Tests Flashcards
(31 cards)
How long is the cell cycle for actively dividing cells (excluding cells in G0)
Approximately 24 Hours
Mitogen
Bioactive protein that can be used to stimulate cells in G0 to enter the cell cycle in vitro (Usually 24 hour lag before cells start cycling post exposure)
e.g. Phytohaemagglutinin A (PHA) - specific to T cells
What is needed for cytogenetic analysis of cells
Fresh cells that are dividing in order to analyse their chromosomes
Cell types usually used for prenatal and postnatal cytogenetic analyses
Postnatal - T cells exposed to mitogen PHA
Prenatal -
Amniotic fluid
Chorionic Villus
Cell types usually used for leukaemia and lymphoma
Leukaemia - Bone marrow
Sometimes blood
Lymphoma - Lymph node biopsy
Bone marrow if BM involved
3 Basic shapes of human metaphase chromosomes
Which chromosome is the smallest
21
It should be 22 but the numbering was done incorrectly at first so it is maintained as per convention
P arm and q arm of chromosome
p arm is short arm (think petite)
q arm is long arm
How is each chromosome subdivided
Into G-bands numbered from the centromere outwards
e.g. q213
Compare number of base pairs and gene loci on X and Y chromosomes
X:
153 Megabase pairs
195 known gene loci
Y:
50 Mb
approx 13 known gene loci (4 in common with X)
X Inactivation
Women switch off one copy of their X chromosomes
Occurs at the 5,000 cell stage of the embryo
Occurs randomly; once established, all daughter cells retain same pattern of inactivation as progenitor
Classic example is tortoiseshell cats
Isochromosome
Chromosome that contains two identical arms joined at the centromere (two p or two q) (abnormal)
Down Syndrome Causes and Frequency
1/650 births
Trisomy 2
Non-Disjunction mostly at maternal meiosis I
(94%)
Robertsonian Translocation - Translocation of parts of chromosome 21
(4%)
Mosaic
Post-zygotic non-disjunction mitotic event
Physical features of down syndrome
Flat facial profile (flattened nose)
Eyes slant upwards
Small ears
Flat back of the head
Protruding tongue (particularly large)
Bilateral single palmar crease
Shorter than average with poor muscle tone
Clinical Features of Down Syndrome
Mild to Moderate Mental Retardation
Frequent ASD
Cardiac Defects
Increased Leukaemic risk
F.I.S.H
Fluoerescence In Situ Hybridisation
Segment of single stranded DNA labelled with fluorescent tag
Hybridises to target DNA attached to a slide with its matching sequence
Edwards Syndrome
3/10,000
Trisomy 18
Growth retardation, prominent occiput (back of head)
Small mouth, clenched hands, overlapping fingers
Prominent heels
Most have congenital heart disease and/or sometimes renal abnormalities
50% die by 2 months
Patau Syndrome
2/10,000
Trisomy 13
Most have scalp defects
Hypotelorism (narrow eye distance)
Most have polydactyly (extra digits)
Cleft lip and palate
Brain malformation (70%)
Congenital heart disease, renal abnormalities, undescended testes
69% die by 6 months
Turner syndrome
Monosomy X
1/10,000 Females
Short stature, webbed neck
Lymphoedema of hands and feet, low posterior hairline, wide carrying angle at elbows, small steep nails
60% have renal abnormalities (Often a single horseshoe shaped liver)
Coarctation of aorta
Gonadal dysgenesis and no secondary sexual development
Wolf Hirschhorn Syndrome
Structural Chromosomal Abnormality
Recurrent Micro-deletion/duplication syndromes
There are a number of such syndromes that arise as de novo events over and over again due to non-allelic homologous recombination (NAHR) (short regions of repeat sequences) events which may ‘confuse’ the DNA systems that lead to commonly seen micro-deletion/duplication syndromes
22q11 Deletion Syndromes
Many names, e.g. Digeorge syndrome
Common deletion but highly variable phenotype
Clefting, Commonly Congenital Heart Disease, Learning difficulties, renal/skeletal abnormalities, skeletal illness, occasionally psychiatric illness without learning difficulties
Characterised by prominent nasal bridge, small mouth
1/4000-5000 births
>15% familial
Prader-willi syndrome
Paternal deletion of proximal long arm of chromosome 15 or if both copies came from mother and no paternal copy
Extremely floppy in early infancy (hypotonia)
Develop marked obesity through over-eating; don’t have the feeling of fullness
Mild-Moderate learning difficulties
Angelman Syndrome
Maternal deletion of proximal long arm of chromosome 15 or two paternal copies with no maternal (UPD) (reverse of prader-willi)
Inappropriate laughter, convulsions, poor coordination (ataxia), Learning difficulties
