7. cytogenetic tests

Question 1

what is a metacentric chromosome

Answer 1

• centromere in the middle

Question 2

what is a submetacentric chromosome

Answer 2

centromere is towards one end

short arms (p) uppermost and long arms (q)

Question 3

what is an acocentric chromosome

Answer 3

centromeres very close to one end

may be a satellite appreance in the short arms

Question 4

how are chromosomes arms divided

Answer 4

into G bands numbered from centromere outwards

Question 5

What is the technique for Fluorescence In Situ Hybridisation.

Answer 5

• 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

Question 6

the difference between male and female karyotypes

Answer 6

females have 46 XX and have more genes as the X chromosome is longer

males have 46 XY

Question 7

How is the dosage disequilibrium balanced out between males and females

Answer 7

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)

Question 8

Nondisjuction

Answer 8

failure of homologous chromosomes or sister chromatids to separate properly during cell division

Question 9

Down syndrome abnormalities

Answer 9

• Trisomy 21

non disjunction at maternal meiotic 1st division

• Unbalanced “robertsonian translocation” - chromosome becomes attached to another
• mosaic

non disjunction

Question 10

Down syndrome clinical features

Answer 10

• 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 11

Edwards syndrome

Answer 11

•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

Question 12

Patau syndrome

Answer 12

•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

Question 13

Turner syndrome

Answer 13

• 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

Question 14

Wolf Hirschhorn Syndrome

Answer 14

• 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

Question 15

How do Recurrent Micro-deletion/duplication Syndromes arise

Answer 15

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.

Question 16

Prader-Willi syndrome

Answer 16

• 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

Question 17

Angelman syndrome

Answer 17

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

Question 18

Two Disorders caused by Uniparental Disomy (UPD), Deletion or Mutation on chromosome 15

Answer 18

Prader Willi syndrome

Angelman syndrome

Question 19

Trisomy rescue

Answer 19

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

Question 20

How can differential gene expression cause disease?

Answer 20

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

Question 21

when can cytogenetic tests be helpful

Answer 21

•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