Imprinting

Question 1

What is imprinting?

Answer 1

An epigenetic phenomenon
- Alteration in gene expression
- Different expression in maternal/paternal genes

Question 2

When does imprinting begin?

Answer 2

During gametogenesis (before fertilization)

Question 3

How are genes ‘marked’ by being of either maternal or paternal origin?

Answer 3

Methylation of cytosine (to make methylcytosine)

Question 4

What is the difference between imprinted and non-imprinted genes?

Answer 4

• Imprinted genes: Only 1 allele expressed
• Non-imprinted genes: Both alleles expressed

Question 5

What 2 syndromes are known as imprinting syndromes?

Answer 5

Prader-Willi and Angelman

Question 6

What part of the genome is affected in PWS and AS?

Answer 6

Chromosome 15q11-q13

Question 7

If the paternal copy of Chromosome 15q11-q13 is abnormal what does this cause?

Answer 7

Prader-Willi

Question 8

If the maternal copy of Chromosome 15q11-q13 is abnormal what does this cause?

Answer 8

Angelman

Question 9

What do p and q represent in relation to the chromosome?

Answer 9

p = short arm (petite)
q = long arm

Question 10

What are the differences in PWS and AS due to?

Answer 10

Imprinting

Question 11

PWS genes are normallyexpressed on what chromosome (paternal or maternal)?

Answer 11

Paternal chr 15
- Not normally expressed on maternal copy

Question 12

UBE3A genes are normally expressed on what chromosome (paternal or maternal)?

Answer 12

Maternal chr 15
- Not normally expressed on paternal copy

Question 13

In PWS what gene loses function?

Answer 13

Paternal copy of PWS gene

Question 14

What are the 2 mechanisms whereby Prader Willi syndrome occurs?

Answer 14

• Deletion of paternal gene, sporadic mutation (75%)
• Maternal uniparental disomy, 2 copies of maternal gene inherited, no paternal gene inherited (25%)

Question 15

What is the most common cause of syndromic obesity?

Answer 15

Prader Willi Syndrome

Question 16

What are the features of PWS?

Answer 16

• Hypotonia (feeding problems, poor suck reflex, delayed milestones)
• Hyperphagia and obesity
• Intellectual disability (mild)
• Hypogonadism (delayed puberty)

Question 17

What chromosome is abnomral in angelman syndrome?

Answer 17

Maternal chr 15 (15q11-q13)

Question 18

What gene has lack of expression in Angelman syndrome?

Answer 18

Maternal UBE3A

Question 19

What are the majority (95-97%) of Angelman syndrome caused by?

Answer 19

Deletions of maternal UBE3A gene (in 15q11-q13 region)

Question 20

What is the less common cause of Angelman syndrome (3-5%)?

Answer 20

Uniparental disomy
- Paternal disomy

Question 21

Why is it less common for Angelman syndrome to occur due to uniparental disomy than PWS?

Answer 21

Paternal disomy is much less common than maternal as non-disjunction is less common in males

Question 22

What are the charactersitics of Angelman syndrome?

Answer 22

• Frequent laughing/smiling
• Seizures (80% of patients)
• Ataxia
• Severe intelectual disability