7. cytogenetic tests Flashcards
what is a metacentric chromosome
- centromere in the middle
what is a submetacentric chromosome
centromere is towards one end
short arms (p) uppermost and long arms (q)
what is an acocentric chromosome
centromeres very close to one end
may be a satellite appreance in the short arms
how are chromosomes arms divided
into G bands numbered from centromere outwards
What is the technique for Fluorescence In Situ Hybridisation.
- A 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 it’s matching DNA sequence
the difference between male and female karyotypes
females have 46 XX and have more genes as the X chromosome is longer
males have 46 XY
How is the dosage disequilibrium balanced out between males and females
if both copies of X were transcribed, females would have twice the dose of gene products than men
X inactivation by swtiching offone copy in females balances this
(causes tortoise shall fur in cats as colour allele is only expressed from active X)
Nondisjuction
failure of homologous chromosomes or sister chromatids to separate properly during cell division
Down syndrome abnormalities
- Trisomy 21
non disjunction at maternal meiotic 1st division
- Unbalanced “robertsonian translocation” - chromosome becomes attached to another
- mosaic
non disjunction
Down syndrome clinical 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
Edwards syndrome
•Growth retardation, prominent occiput (back of
head)
- Small mouth, clenched hands, overlapping fingers,
- Prominent heels (rocker bottom feet)
•Congenital heart disease (85%), renal anomalies
(30%)
•50% die by 2 months of age
Trisomy 18 47XX, +18
Patau syndrome
•Scalp defects, hypotelorism (narrow distance
between eyes), polydactyly (extra digits),
cleft lip and palate
•Holoprosencephaly (brain malformation),
congenital heart disease, renal anomalies,
undescended testes
•69% die by 6 months
trisomy 13
Turner syndrome
- Short stature, webbed neck, lymphoedema of hands and feet, low posterior hairline, wide carrying angle at elbows, small nails
- Renal anomalies, coarctation of aorta, bicuspid aortic valve, gonadal dysgenesis
female missing X chromosome
Wolf Hirschhorn Syndrome
- Terminal deletion – critical region 4p16.3
- Prominent forehead, wide-set eyes (hypertelorism), and broad beaked nose, collectively described as “Greek warrior helmet” features. Severe MR
How do Recurrent Micro-deletion/duplication Syndromes arise
de novo events as the result of Non-allelic Homologous Recombination (NAHR) events between polymorphic regions of low copy repeats (LCRs). The presence of two LCRs within close proximity will pre-dispose to NAHR resulting in either deletion or duplication of the intervening sequence.
Prader-Willi syndrome
- Paternal deletion of proximal long arm of chromosome 15, or maternal chromosome 15 UPD uniparental disomy
- 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 chromosome 15 UPD
- Inappropriate laughter
- Convulsions
- Poor coordination (ataxia)
- Learning difficulties
Two Disorders caused by Uniparental Disomy (UPD), Deletion or Mutation on chromosome 15
Prader Willi syndrome
Angelman syndrome
Trisomy rescue
fertilized ovum containing three copies of a chromosome loses one of these chromosomes to form a normal, diploid chromosome
but can result in uniparental disomy
How can differential gene expression cause disease?
if expressed gene is absent (due to chromosomal deletion or uniparental disomy)
controlled by methylation
•Some genes are only expressed on the chromosome that is inherited from either the mother or father
when can cytogenetic tests be helpful
•Learning difficulties/Congenital abnormalities
–Cytogenetic syndromes – diagnosis/prognosis
–Chromosome deletions/duplications – diagnosis/genes
•Recurrent miscarriage
–Carrier of chromosome rearrangement – recurrence risk
•Infertility
–Sex chromosome abnormality, marker chromosome, carrier of large chromosome rearrangement
•Prenatal diagnosis
–Trisomy (eg. Down Syndrome risk), or unbalanced familial chromosome rearrangement
