ChromosOmics - Database
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                                                           ABOUT IMPRINTING                                                          

Imprinting - Background

"Causative trans-acting factors in imprinting disorders have the potential to globally dysregulate epigenetic processes, thus affecting multiple DMRs across the genome. This is called a multi-locus imprinting disturbance (MLID). MLID is detected in over 10 % of patients with imprinting disorders such as TNDM, BWS, and SRS, which are frequently caused by epigenetic errors. It is often observed only in a fraction of somatic cells. Similar to UPDs, the mosaic nature of MLID argues for an origin of the underlying defect early in development." (Cited from {1279})

In 12/39 cases with UPD in any of the imprinted chromosomes (30.8%), skewed X-chromosome inactivation was observed {1176}.

In babies born after applying assisted reproductive techniques imprinting is 15x more frequent than in babies born after natural conception {879}; for BWS it was determined a 10 fold risk in ART - but no clear data on how many were due to UPD {1012}.


In {1227} the theory of Denise Barlow from 1993 is again revisited, where he proposed that genomic imprinting might have arisen from a host defense mechanism designed to inactivate retrotransposons.


Summary of all known imprinting disorders by 2016 see {987}.
Summary of all potentially imprinted regions in human (on all chromosomes) see {1074}.
A 'high-resolution map of genomic imprinting' was published in 2019 {1140}.
 For known imprinted genes see http://www.geneimprint.com/site/genes-by-species.Homo+sapiens or http://igc.otago.ac.nz/Search.html.

Imprinting disorders

Diagnostics for imprinting disorders is reviewed in 2020 in {1280}

It turns out that imprinting disorders show overlapping phenotypes {1266}.
Also, UPD(all)pat leads primarily to BWS like symptoms and UPD(all)mat leads to SRS-like phenotype.

The following list of imprinting disorders is based on {1280; 1281}
(abbreviations in Table below: alt = altered; DMR = differentially methylated region; Ex1 = exon 1; GOM = gain of methylation, hypermethylation;

  LOM = loss of methylation, hypomethylation; TSS = alternative transcription start site)
imprinting disorder
gene(s) involved
locus
mosaic
mechanisms
Transient Neonatal Diabetes mellitus (TNDM)(familial)
PLAGL:alt-TSS-DMR, LOM*
ZFP57
+
6q24
no
UPD(6)pat
dup(6q)pat
imprinting center defect*
single nucleotid variant+
Birk-Barel intellectual disability syndrome (BBIDS)
KCNK9+ 8q24
no
single nucleotid variants+
Silver-Russell syndrome (SRS)
GRB10:alt-TSS-DMR, GOM*
7
no
UPD(7)mat
dup(7p and or q)mat
imprinting center defect*
HG19/IGF2:TSS-DMR, LOM*
KCNQ10T1:TSS-DMR, GOM*
CDKN1C+
IGF2+
HMGA2
+
PLAG1
+
11p15.5
yes
UPD(11p15)mat
dup(11p)mat
imprinting center defect*
single nucleotid variant+
Beckwith-Wiedemann syndrome (BWS)
GRB10:alt-TSS-DMR, GOM*
HG19/IGF2:TSS-DMR, GOM*
KCNQ10T1:TSS-DMR, LOM*
CDKN1C+ mat
11p15.5
yes
UPD(11p15)pat
dup(11p)pat
imprinting center defect*
single nucleotid variant+
no syndrome yet
but imprinting
RB1
13q14.2
no
UPD(13)mat {1372}
Temple syndrome (TS14)
MEG3/DLK1:TSS-DMR, LOM*
14q32
no
UPD(14)mat
del(14q32)pat
imprinting center defect*
Kagami-Ogata syndrome (KOS14)
MEG3/DLK1:TSS-DMR, GOM* 14q32
yes
UPD(14)pat
del(14q32)mat
imprinting center defect*
(familial) Central Precocious Puberty (CPPB)
DLK1+ mat 14q32 no
del or dup(14q32)
single nucleotid variant+
Prader-Willi syndrome (PWS)
SNURF:TSS-DMR, GOM*
15q11q13
yes
UPD(15)mat
del(15q11q13)pat
imprinting center defect*
Angelman syndrome (AS)
SNURF:TSS-DMR, LOM*
UBE3A
+ mat
15q11q13 yes UPD(15)pat
del(
15q11q13)mat
 imprinting center defect*
single nucleotid variant+
Central Precocious Puberty 2 (CPPB2)
MKRN3+ pat 15q11.2 no
single nucleotid variant+
Schaaf-Yang syndrome (SHFYNG)
MAGEL2+ pat 15q11.2 no
single nucleotid variant+
Pseudo-hypoparathyoridism type 1B (PHP1B)
GNAS-NESP:TSS-DMR, GOM*
GNAS-AS1:
TSS-DMR, LOM*
GNAS-XL:Ex1-DMR, GOM*
GNAS
+
20q13
yes
UPD(20)pat
del(20q13)mat
imprinting center defect*
single nucleotid variant+
Mulchandani-Bhoi-Conlin syndrome (MBCS)
n.a.
6q24
no
UPD(20)mat
multilocus imprinting disturbance (MLID)   they can show mixture of all above mentioned imprinting disorders or main features of only one of them

 

New potential regions underlying imprinting

Chromosomal region
Gene
Reference
1p36.32 TP73 1195
1p31.3 DIRAS3 1195
6q25.3 SLC22A3 1195
7p12.2 DDC 1195
7p12.1 GRB10 1195
7q21.11 MAGI2 1195
7q21.3 PEG10 1195
7q21.3 PPP1R9A 1195
7q21.3 CALCR 1195
8p23.3 DLGAP2 1195
9p24.2 GLIS3 1195
10q26.11 INPP5F 1195
11q13.3
ANO1 1195
12q13.11 SLC38A4 1195
15q21.1
GATM 1195
19q13.43 PEG3 1195
19q13.42 NLRP2 1195

In {1373} potential yet undetected regions in the genome with uniparental gene expression are summarized.
Neither the words 'epigenetics' nor 'UPD' are mentioned there, even though 'parent of origin-effects' are discussed.


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