Genomic imprinting

Question 1

T/F. At most autosomal loci, both alleles are, together, either active or inactive, but at approximately 100 loci, only one allele is active.

Answer 1

True.

Question 2

In loci where only one allele is active, the allele chosen for inactivation depends upon its ____.

Answer 2

parental origin

Question 3

Only the paternally inherited allele of the ____ gene on 11p is active.

Answer 3

insulin growth factor 2 ( IGF2 )

Question 4

The imprinting of IGF2 gene is established during gametogenesis and, as with other imprinted genes, involves ____ differences at specific sites adjacent to the gene.

Answer 4

methylation

Question 5

Methylation for allele inactivation in the germ line may be determined by specific secondary DNA structures resulting from the ____ that are found close to both maternally and paternally methylated _____.

Answer 5

short direct repeat sequences; imprinting control regions (ICRs) or imprinting control centres.

Question 6

IGF2 expression is prevented on the maternal allele because a nearby ICR is able, in its unmethylated state, to bind a so - called ____.

Answer 6

boundary factor, CTCF.

Question 7

A deletion of the proximal long arm of chromosome 15 on a maternal chromosome results in mental handicap and clinical features of ____, whereas a similar deletion on a paternal chromosome results in a clinically distinct condition called ____.

Answer 7

Angelman syndrome; Prader – Willi syndrome

Question 7

How does CTCF and methylation regulate allele-specific expression of insulin growth factor 2?

Answer 7

In maternal allele –> ICR is unmethylated –> boundary factor, CTCF binds to ICR –> inhibits interaction of IGF2 promoter with enhancer –> non expression

In paternal allele –> ICR is methylated –> prevents boundary factor, CTCF from binding to ICR –> IGF2 promoter is free to interact with enhancer –> expression

Question 8

What are the genes expressed only in the paternal proximal long arm of the chromosome 15, deletion of which results in Prader – Willi syndrome.

Answer 8

SNRPN , MKRN3 , NDN and MAGEL2

Question 8

T/F. H19 promoter competes with that of IGF2 for the same enhancers.

Answer 8

True. This leads to the reciprocal regulation of H19 gene in the paternal allele.

Question 9

What is the genes expressed only in the maternal proximal long arm of the chromosome 15, deletion of which results in Angelman syndrome.

Answer 9

UBE3A

Question 10

The most extreme imbalance of maternal and paternal contributions occurs in ____, w/c have a double paternal contribution and no maternal contribution.

Answer 10

hydatidiform moles

Question 11

T/F. In Angelman’s syndrome, an electroencephalogram is only sometimes abnormal with posterior high – voltage sharp waves and a posterior spike and wave on eye closure.

Answer 11

False. Always abnormal electroencephalograms

Question 12

This syndrome is characterized by developmental delay, very poor speech, jerky movements, paroxysms of inappropriate laughter, reduced hair & skin pigmentation, facial dysmorphisms & microcephaly.

Answer 12

Angelman’s syndrome

Question 12

50% of patients with Angelman’s syndrome show a visible cytogenetic microdeletion at ____.

Answer 12

15q12

Question 13

What is the frequency of incidence of Angelman’s syndrome?

Answer 13

1 in 20, 000

Question 14

In this genetic cause of Angelman’s syndrome, both copies of chromosome 15 are contributed by the father.

Answer 14

paternal uniparental disomy

Question 15

Other genetic causes of Angelman’s syndrome

Answer 15

uniparental disomy; mutation in the UBE3A gene; imprinting defect

Question 16

The recurrence risk for Angelman in families with a de novo deletion is low, w/ familial recurrences being more likely if:

Answer 16

a parent possesses a chromosomal translocation

proband possesses an inherited UBE3A mutation

proband possesses an inherited imprinting control region (ICR) deletion .

Question 17

This gene encodes a ubiquitin protein ligase enzyme that normally catalyses the marking of specific proteins (w/ ubiquitin tags) for subsequent degradation.

Answer 17

UBE3A

Question 18

In newborns with this syndrome, hypotonia and poor swallowing may be marked. The face is flat with a tented upper lip, and the external genitalia are hypoplastic. In later childhood, the hypotonia improves and overeating with obesity occurs.

Answer 18

Prader-Willi syndrome

Question 19

In patients with Prader-Willi syndrome, the forehead tends to be prominent with ____ narrowing. The ____ are almond - shaped and the hands and feet are small.

Answer 19

bitemporal; palpebral fissures

Question 20

In patients with Prader-Willi syndrome, mental handicap is usual, with an IQ range of ____ and a mean of ____.

Answer 20

20 – 80; 50

Question 21

Frequency of incidence of Prader-Willi?

Answer 21

1 in 10,000

Question 22

In 50% of patients with Prader-Willi syndrome, cytogenetic microdeletion is apparent at ____.

Answer 22

15q11 – 13

Question 23

T/F. In Prader-Willi syndrome, recurrence is very likely where the child has a de novo deletion, and 2% arise from a parental structural rearrangement and here prenatal diagnosis needs to be considered.

Answer 23

False. Unlikely recurrence in cases where deletion is de novo.

Question 24

Other genetic causes of Prader-Willi Syndrome other than de novo deletion of 15q11-13

Answer 24

Maternal uniparental disomy ICR mutation or ICR microdelection

Question 25

The genetic consequent of Prader-Willi syndrome is the lack of paternally expressed genes such as ____, a small nuclear ribonucleoprotein gene involved in alternative mRNA splicing.

Answer 25

SNRPN