Imprinting and Uniparental Disomy

Question 1

_____________ is the mechanism for “turning on or off” genes long term

Answer 1

epigenetics

Question 2

Epigenetics includes ____________ mRNAs, _____________ deacetylation/modification, __________ methylation and _____________modification

Answer 2

noncoding mRNAs
histone deacetylation
DNA methylation
chromatin modification

Question 3

_______________ __________________ is when one parental allele is inactivated at a specific locus

Answer 3

parental imprinting
= functional hemizygosity

Question 4

There are approximately _________ imprinted genes

Answer 4

128

Question 5

Imprinting is reversed during _________________

Answer 5

gametogenesis

Question 6

Imprinted genes encode for ______________ and proteins

Answer 6

RNA
ex XIST

Question 7

Imprinted genes cluster on chromosomes __, __, __, __, __ & __

Answer 7

6, 7, 11, 14, 15 and 20

Question 8

The largest imprinted gene cluster is on chromosome _________________

Answer 8

11p15

Question 9

_________ ____________ ____________ work by controlling nearby gene, binding Cis-acting elements and DNA methylation/histone deacetylation

Answer 9

imprinting control regions (ICRs)
or IC centers (ICCs)

Question 10

Methylation occurs on the __________ site of CpG

Answer 10

5 prime methylcytosine

Question 11

Imprinting disorders can be caused by ____________ or _____________, __________ disomy, mutations of single ________ genes and mutations of the __________ center

Answer 11

deletions/duplications
uniparental disomy
single imprinted genes
imprinting center

Question 12

__________ ______________ is when both chromosome copies from same parent

Answer 12

uniparental disomy

Question 13

Uniparental disomy is ____________ in spontaneous abortions (

Answer 13

rare (0.2-0.3%)

Question 14

______________ _________________ is one reason why cloned animals have so many problems

Answer 14

uniparental disomy
only maternal genes

Question 15

Beyond trisomy rescue, there is also __________ rescue that is a source of uniparental disomy

Answer 15

monosomy
isodisomy - risk for imprinting and AR disorders

Question 15

There is a __________ chance of uniparental disomy with NDJ in meiosis I and trisomy rescue (deletion of 1/3 chromosomes)

Answer 15

1/3
other two times you get biparental
heterodisomy - risk for imprinting disorders but not AR

Question 16

65% of UPD cases have _____________ karyotype

Answer 16

normal

Question 17

Testing for UPD may need to include both ____________ and ___________analysis!

Answer 17

molecular and chromosome

Question 18

SNP microarray can detect UPD, but cannot detect ___________

Answer 18

rearrangements

Question 19

Chromosomes will not detect ____________, but will find rearrangements

Answer 19

UPD

Question 20

______________ is caused by paternal UPD 15 (15q11.2) and deletion of the maternal allele

Answer 20

Angelman syndrome

Question 21

______________ is caused by maternal UPD 15 (15q11.2) and deletion of the paternal allele

Answer 21

Prader-Willi

Question 22

Gene associated with Angelman syndrome

Answer 22

UBE3A

Question 23

_____________________ is caused by paternal UPD at 11q15 and loss of maternal CDKN1C

Answer 23

Beckwith Wiedemann syndrome

Question 24

____________________ is caused by maternal UPD at 11q15 or 7q32 and loss of paternal input

Answer 24

Russell-Silver

Question 25

_____________________ is caused by maternal UPD at 14q32 and loss of paternal MEG3

Answer 25

Temple syndrome

Question 26

_____________________ is caused by paternal UPD at 14q32 and loss of maternal DLK1

Answer 26

Kagami-Otaga syndrome

Question 27

Prader-Willi syndrome is a ________________________ disorder with ID, hypothalamic dysfunction, hyperphagia, behavioral disorder, hypopigmentation and short stature with advanced puzzle skills

Answer 27

neuroendocrine

Question 28

Angelmann syndrome is a __________________ disorder associated with severe ID, seizures, hand flapping, frequent smiling/laughing, hypopigmentation and water fascination

Answer 28

neurobehavioral

Question 29

Prader-Willi and Angelmann syndrome are ________________ and therefore risk for recurrence is low

Answer 29

sporadic

Question 30

_______________ disrupt normal epigenetics

Answer 30

epimutations

Question 31

Imprinting center mutations ______________ the risk for recurrence to _____%

Answer 31

increase
50%

Question 32

PWS testing starts with ________________ (99% detected) and then proceeds to MLPA/FISH/CPA due to the most common cause as ______________, then UPD and IC sequencing

Answer 32

methylation
deletion

Question 33

Like ICR mutations, de novo chromosomal translocations in PWS/AS regions on 15q11.2 is associated with a risk of __________ to ______________%

Answer 33

25 to 50%

Question 34

Angelmann testing can start with methylation studies and proceed as PWS unless there is no methylation and then sequencing and del/dup studies in the _______________ gene should be performed

Answer 34

UBE3A

Question 35

Risk of Angelmann syndrome with a paternal 15;15 Rob translocation

Answer 35

~100%

Question 36

Beckwith-Wiedemann syndrome is an ________________ disorder caused by ____________ UPD on 11p15 with macroglossia, omphalocele, hemihypertrophy, Wilms tumor or nephroblastoma, placental mesenchymal dyplasia, adrenal cortex cytomegaly and pancreatic adenomatosis, adrenocortical carcinoma, pheochromocytoma, hepatoblastoma and rhabdomyosarcoma

Answer 36

overgrowth
paternal

Question 37

Beckwith Wiedemann most commonly from a loss of methylation of ________ followed by _____________ UPD and then gain of methylation of _______________

Answer 37

IC2 (maternal) loss of methylation and gain of IGF2 expression - 50%
paternal UPD -20%
IC1 (maternal) gain of methylation -5%
5% maternal CDKN1C mutation

Question 38

BWS testing starts with ________ then goes to CMA, ______ and ____________ sequencing

Answer 38

methylation
UPD
CDKN1C

Question 39

Familial BWS is most likely (40%) caused by _________________

Answer 39

CDKN1C mutations

Question 40

Russell Silver is an ___________________ disorder from ____________ UPD of 11p15 or 7 with urogenital disorders and a triangular face

Answer 40

undergrowth
maternal UPD (loss of paternal)

Question 40

Russell Silver syndrome is a result of loss of paternal ______________ expression

Answer 40

IGF2

Question 41

The #1 cause of Russell Silver syndrome (45%)
The next most common cause is _______________ UPD (5-10%)

Answer 41

Loss of IC1 methylation on 11p15
maternal UPD7

Question 42

Paternal IC2 11p15 methylation defect risk for daughter or when germline epimutations

Answer 42

50%

Question 43

Temple syndrome is a result of _____________ UPD on Chr 14 with growth restriction and truncal obesity as adult

Answer 43

maternal UPD

Question 44

Kagami-Ogata syndrome is a result of _____________UPD on Chr 14 with bell shaped chest, coat-hanger ribs and limited survival

Answer 44

paternal UPD

Question 44

CFTR was discovered due to isodisomy on chromosome ____________ and RSS

Answer 44

Chromosome 7

Question 45

In genome wide UPD, ______________ is where parental pronucleus mitoses and the organism splits into UPD sperm and normal sperm/egg 46–

Answer 45

endoduplication

Question 46

Genome wide UPD must be _______________

Answer 46

mosaic

Question 47

______________ is hypomethylation of multiple imprinted loci

Answer 47

HIL