Genomic Imprinting & Uniparental Disomy

Question 1

What is Prader-Wili syndrome?

Answer 1

caused by del(15)(q11q13).
hypotonia and feeding difficulties, hypogonadism in infancy
Later child develops uncontrollable apetite, mental retardation.

Question 2

What is angelman syndrome?

Answer 2

spasticity, seizures, mental retardation, caused by del (15(q11q13) exact same as Prader-Wili syndrome.

Question 3

What is imprinting?

Answer 3

Differntial gene expression that is dependent on parental origin. In some cases, only one parent’s gene copy is expressed. epigenitic process (heritable but reversible) DNA methylation is a common mechanism.

Question 4

What are two examples of imprinted genes?

Answer 4

IGF2 (insulin-like growth factor type 2) only paternal copy expressed.
KVLQT1 (potassium channel gene mutated in long QT syndrome) maternal copy expressed., but biallelic expression in heart.

Question 5

If SNRPN gene is maternally imprinted, does the child have the paternal or maternal gene expressed?

Answer 5

If maternally imprinted, the maternal copy is turned off and only the paternal copy is expressed.

Question 6

What is SNRPN?

Answer 6

small nuclear ribonucleoprotein polypeptide N. Paternal copy expressed

Question 7

What is UBE3A?

Answer 7

ubiquitin protein ligase 3. Maternal copy expressed in brain, both copies elsewhere.

Question 8

What is imprinting control region?

Answer 8

small region on genome that controls imprinting by methylation on different spots. Has different controls for male and female gametogenesis

Question 9

Describe the steps of the imprinting cycle.

Answer 9

1. imprint switch during gametogenesis
2. pattern maintained throughout development and in the somatic tissues of the adult
3. in gametes, the imprint is reset for the next generation.

Question 10

What usually causes Prader-Willi Syndrome? Is it maternal or paternal usually?

Answer 10

(no functional copy of SNRPN gene)
70% of the time it is paternal microdeletion
28% of the time maternal uniparental disomy
2% mutation of imprinting center

Question 11

What is maternal uniparental disomy?

Answer 11

two copies from the same parent. Will still have normal chromosome number, but both will be from mother and none from father. Very rare. Have to be at least 2 independent errors for it to occur.

Question 12

What is most common cause of angelman syndrome?

Answer 12

(no functional copy of the UBE3A gene)
70% maternal deletion of 15q12
5% paternal uniparental disomy
5% mutation of imprinting center
10% UBE3A point mutations

Question 13

What can cause uniparental disomy?

Answer 13

trisomy rescue