More Stories from the Genetics Clinic

Question 1

What happens if the full genome of an embryo derives from one parent and what is the significance of this finding?

Answer 1

Paternal – hydatidiform mole
Maternal – ovarian teratoma
Shows that the origin of the parental DNA is important

Question 2

What is the mechanism of imprinting?

Answer 2

DNA Methylation

Question 3

Which base gets methylated?

Answer 3

5’ position on the pyrimidine ring of the cytosine

Question 4

What is the general effect of methylation on the gene promoter?

Answer 4

Repressed gene transcription

Question 5

The loss of function of a gene on which chromosome causes Prader-Willi and Angelman Syndrome?

Answer 5

Chromosome 15

Question 6

State some symptoms of Prader-Willi Syndrome

Answer 6

Hyperphagia 
Obesity 
Mental Retardedness 
Short Stature 
Hypotonia 
Infertility

Question 7

State some symptoms of Angelman Syndrome.

Answer 7

• Developmental delay and speech impairment
• Movement disorder (gait ataxia)
• Behavioral uniqueness: happy demeanor; excitable, short attention span

Question 8

What are the three possible causes of Prader-Willi and Angelman Syndrome?

Answer 8

Deletion of the PWS/AS critical region on chromosome 15
Uniparental isodisomy
Other mechanisms e.g. translocations

Question 9

Describe how uniparental isodisomy can lead to Prader-Willi and Angelman Syndrome.

Answer 9

Non-disjunction in meiosis 2 makes a gamete that has two copies of chromosome 15 resulting in a zygote with three copies of chromosome 15. Failure to remove the duplicated chromosome results in the zygote having two copies of chromosome 15 from the same parent.

Question 10

How is PWS and AS diagnosed? Which genes near/in the PWS/AS critical region are used?

Answer 10

FISH – fluorescence in situ hybridisation
OR methylation specific PCR
PML (promyelocytic leukaemia) gene is just outside the PWS/AS critical region snRNP (small nuclear ribonucleoprotein) gene is inside the PWS/AS critical region

Question 11

What phenomenon determines the severity of mitochondrial disease?

Answer 11

Heteroplasmy

Question 12

State two examples of mitochondrial disease

Answer 12

MELAS and LHON

Question 13

State some symptoms of MELAS.

Answer 13

Mitochondrial encephalomyopathy (muscle weakness)
Lactic Acidosis (vomiting, diarrhoea)
Stroke
Episodic seizures, headache, hemiparesis

Question 14

What mutations cause MELAS?

Answer 14

MTTL1 – tRNA translated codon as Phenylalanine instead of leucine
MTND1 and MTND5 – NADH Dehydrogenase subunits 1 and 5

Question 15

State some symptoms of LHON

Answer 15

Painless bilateral loss of central vision leading to blindness

Question 16

Mutations in what genes cause LHON?

Answer 16

MTND1, 4,5 and 6 – NADH Dehydrogenase subunits 1, 4, 5 and 6
MTCYB – cytochrome B

Question 17

Give two examples of inborn errors of metabolism.

Answer 17

Phenylketonuria and MCAD deficiency

Question 18

State some symptoms of Phenylketonuria

Answer 18

Mental retardation
Blonde hair/blue eyes
Eczema

Question 19

How is phenylketonuria detected?

Answer 19

Elevated levels of phenylalanine in the blood

Question 20

What is the treatment for PKU?

Answer 20

Remove phenylalanine from the diet

Question 21

What is a common feature of MCAD Deficiency?

Answer 21

Episodic Hypoketotic Hypoglycaemia

Question 22

A mutation in which gene causes MCAD Deficiency?

Answer 22

ACADM

Question 23

What is the treatment for MCAD Deficiency?

Answer 23

Maintain adequate calorie intake to prevent the body from switching to beta-oxidation.