Imprinting and Uniparental Disomy Flashcards
_____________ is the mechanism for “turning on or off” genes long term
epigenetics
Epigenetics includes ____________ mRNAs, _____________ deacetylation/modification, __________ methylation and _____________modification
noncoding mRNAs
histone deacetylation
DNA methylation
chromatin modification
_______________ __________________ is when one parental allele is inactivated at a specific locus
parental imprinting
= functional hemizygosity
There are approximately _________ imprinted genes
128
Imprinting is reversed during _________________
gametogenesis
Imprinted genes encode for ______________ and proteins
RNA
ex XIST
Imprinted genes cluster on chromosomes __, __, __, __, __ & __
6, 7, 11, 14, 15 and 20
The largest imprinted gene cluster is on chromosome _________________
11p15
_________ ____________ ____________ work by controlling nearby gene, binding Cis-acting elements and DNA methylation/histone deacetylation
imprinting control regions (ICRs)
or IC centers (ICCs)
Methylation occurs on the __________ site of CpG
5 prime methylcytosine
Imprinting disorders can be caused by ____________ or _____________, __________ disomy, mutations of single ________ genes and mutations of the __________ center
deletions/duplications
uniparental disomy
single imprinted genes
imprinting center
__________ ______________ is when both chromosome copies from same parent
uniparental disomy
Uniparental disomy is ____________ in spontaneous abortions (
rare (0.2-0.3%)
______________ _________________ is one reason why cloned animals have so many problems
uniparental disomy
only maternal genes
Beyond trisomy rescue, there is also __________ rescue that is a source of uniparental disomy
monosomy
isodisomy - risk for imprinting and AR disorders
There is a __________ chance of uniparental disomy with NDJ in meiosis I and trisomy rescue (deletion of 1/3 chromosomes)
1/3
other two times you get biparental
heterodisomy - risk for imprinting disorders but not AR
65% of UPD cases have _____________ karyotype
normal
Testing for UPD may need to include both ____________ and ___________analysis!
molecular and chromosome
SNP microarray can detect UPD, but cannot detect ___________
rearrangements
Chromosomes will not detect ____________, but will find rearrangements
UPD
______________ is caused by paternal UPD 15 (15q11.2) and deletion of the maternal allele
Angelman syndrome
______________ is caused by maternal UPD 15 (15q11.2) and deletion of the paternal allele
Prader-Willi
Gene associated with Angelman syndrome
UBE3A
_____________________ is caused by paternal UPD at 11q15 and loss of maternal CDKN1C
Beckwith Wiedemann syndrome
____________________ is caused by maternal UPD at 11q15 or 7q32 and loss of paternal input
Russell-Silver
_____________________ is caused by maternal UPD at 14q32 and loss of paternal MEG3
Temple syndrome
_____________________ is caused by paternal UPD at 14q32 and loss of maternal DLK1
Kagami-Otaga syndrome
Prader-Willi syndrome is a ________________________ disorder with ID, hypothalamic dysfunction, hyperphagia, behavioral disorder, hypopigmentation and short stature with advanced puzzle skills
neuroendocrine
Angelmann syndrome is a __________________ disorder associated with severe ID, seizures, hand flapping, frequent smiling/laughing, hypopigmentation and water fascination
neurobehavioral
Prader-Willi and Angelmann syndrome are ________________ and therefore risk for recurrence is low
sporadic
_______________ disrupt normal epigenetics
epimutations
Imprinting center mutations ______________ the risk for recurrence to _____%
increase
50%
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
methylation
deletion
Like ICR mutations, de novo chromosomal translocations in PWS/AS regions on 15q11.2 is associated with a risk of __________ to ______________%
25 to 50%
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
UBE3A
Risk of Angelmann syndrome with a paternal 15;15 Rob translocation
~100%
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
overgrowth
paternal
Beckwith Wiedemann most commonly from a loss of methylation of ________ followed by _____________ UPD and then gain of methylation of _______________
IC2 (maternal) loss of methylation and gain of IGF2 expression - 50%
paternal UPD -20%
IC1 (maternal) gain of methylation -5%
5% maternal CDKN1C mutation
BWS testing starts with ________ then goes to CMA, ______ and ____________ sequencing
methylation
UPD
CDKN1C
Familial BWS is most likely (40%) caused by _________________
CDKN1C mutations
Russell Silver is an ___________________ disorder from ____________ UPD of 11p15 or 7 with urogenital disorders and a triangular face
undergrowth
maternal UPD (loss of paternal)
Russell Silver syndrome is a result of loss of paternal ______________ expression
IGF2
The #1 cause of Russell Silver syndrome (45%)
The next most common cause is _______________ UPD (5-10%)
Loss of IC1 methylation on 11p15
maternal UPD7
Paternal IC2 11p15 methylation defect risk for daughter or when germline epimutations
50%
Temple syndrome is a result of _____________ UPD on Chr 14 with growth restriction and truncal obesity as adult
maternal UPD
Kagami-Ogata syndrome is a result of _____________UPD on Chr 14 with bell shaped chest, coat-hanger ribs and limited survival
paternal UPD
CFTR was discovered due to isodisomy on chromosome ____________ and RSS
Chromosome 7
In genome wide UPD, ______________ is where parental pronucleus mitoses and the organism splits into UPD sperm and normal sperm/egg 46–
endoduplication
Genome wide UPD must be _______________
mosaic
______________ is hypomethylation of multiple imprinted loci
HIL
