Imprinting and Uniparental Disomy Flashcards

1
Q

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

A

epigenetics

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2
Q

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

A

noncoding mRNAs
histone deacetylation
DNA methylation
chromatin modification

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3
Q

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

A

parental imprinting
= functional hemizygosity

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4
Q

There are approximately _________ imprinted genes

A

128

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5
Q

Imprinting is reversed during _________________

A

gametogenesis

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6
Q

Imprinted genes encode for ______________ and proteins

A

RNA
ex XIST

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7
Q

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

A

6, 7, 11, 14, 15 and 20

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8
Q

The largest imprinted gene cluster is on chromosome _________________

A

11p15

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9
Q

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

A

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

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10
Q

Methylation occurs on the __________ site of CpG

A

5 prime methylcytosine

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11
Q

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

A

deletions/duplications
uniparental disomy
single imprinted genes
imprinting center

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12
Q

__________ ______________ is when both chromosome copies from same parent

A

uniparental disomy

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13
Q

Uniparental disomy is ____________ in spontaneous abortions (

A

rare (0.2-0.3%)

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14
Q

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

A

uniparental disomy
only maternal genes

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15
Q

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

A

monosomy
isodisomy - risk for imprinting and AR disorders

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15
Q

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

A

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

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16
Q

65% of UPD cases have _____________ karyotype

A

normal

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17
Q

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

A

molecular and chromosome

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18
Q

SNP microarray can detect UPD, but cannot detect ___________

A

rearrangements

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19
Q

Chromosomes will not detect ____________, but will find rearrangements

A

UPD

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20
Q

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

A

Angelman syndrome

21
Q

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

A

Prader-Willi

22
Q

Gene associated with Angelman syndrome

A

UBE3A

23
Q

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

A

Beckwith Wiedemann syndrome

24
Q

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

A

Russell-Silver

25
Q

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

A

Temple syndrome

26
Q

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

A

Kagami-Otaga syndrome

27
Q

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

A

neuroendocrine

28
Q

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

A

neurobehavioral

29
Q

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

A

sporadic

30
Q

_______________ disrupt normal epigenetics

A

epimutations

31
Q

Imprinting center mutations ______________ the risk for recurrence to _____%

A

increase
50%

32
Q

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

A

methylation
deletion

33
Q

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

A

25 to 50%

34
Q

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

A

UBE3A

35
Q

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

A

~100%

36
Q

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

A

overgrowth
paternal

37
Q

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

A

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

38
Q

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

A

methylation
UPD
CDKN1C

39
Q

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

A

CDKN1C mutations

40
Q

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

A

undergrowth
maternal UPD (loss of paternal)

40
Q

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

A

IGF2

41
Q

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

A

Loss of IC1 methylation on 11p15
maternal UPD7

42
Q

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

A

50%

43
Q

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

A

maternal UPD

44
Q

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

A

paternal UPD

44
Q

CFTR was discovered due to isodisomy on chromosome ____________ and RSS

A

Chromosome 7

45
Q

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

A

endoduplication

46
Q

Genome wide UPD must be _______________

A

mosaic

47
Q

______________ is hypomethylation of multiple imprinted loci

A

HIL

48
Q
A