Part of the Imprinting track collection, this track shows the 48 human germline imprinted differentially methylated regions (DMRs) listed in the joint statement of European and international experts on multi-locus imprinting disturbance (MLID), the condition in which methylation at several imprinted loci is changed at once. The list is a more recent counterpart of the Monk et al. 2018 set and can be compared with it. The two lists largely name the same regions, with identical hg38 coordinates for 48 of them.
Each region is classified by whether methylation at the region is used in diagnosis. A clinically associated DMR is one where a change in methylation is directly associated with an imprinting disorder, or is used as a proxy to detect imprinting disturbance. A non-clinical DMR is not currently associated with a clinical phenotype or used in diagnosis. For the clinically associated regions the track gives the imprinting disorders in which they are involved, with the disorder acronyms of the paper expanded to full names.
The color shows the parent whose allele is methylated, and the shade shows the classification:
| Red — clinically associated DMR, maternal allele methylated | |
| Blue — clinically associated DMR, paternal allele methylated | |
| Light red — non-clinical DMR, maternal allele methylated | |
| Light blue — non-clinical DMR, paternal allele methylated |
The track can be filtered by clinical classification, methylated allele and imprint origin. The imprint origin says whether the methylation is established in the oocyte or in the sperm (germline DMR), or only after fertilization (secondary DMR). The details page also shows the type given in Table 1 of the paper (clinically associated, non-clinical, or variable methylation that cannot be interpreted clinically), whether the region is marked as the key diagnostic DMR of its locus, and the other names used for the region in the literature.
The imprinting disorders named in the track are described in Table 2 of the paper:
| Disorder | Chromosome | Prevalence | OMIM |
|---|---|---|---|
| Beckwith-Wiedemann syndrome (BWS) | 11p15.5 | 1:10,000 to 1:80,000 | 130650 |
| Silver-Russell syndrome (SRS) | 11p15.5, chr7 | 1:16,000 | 180860 |
| Transient neonatal diabetes mellitus type 1 (TNDM) | 6q24 | 1:15,000 to 1:400,000 | 601410 |
| Pseudohypoparathyroidism type 1b (PHP) | 20q13.3 | not known | 603233 |
| Temple syndrome (TS14) | 14q32 | not known | 616222 |
| Kagami-Ogata syndrome (KOS14) | 14q32 | not known | 608140 |
| Angelman syndrome (AS) | 15q11.2 | 1:25,000 to 1:40,000 | 105830 |
| Prader-Willi syndrome (PWS) | 15q11.2 | 1:8,000 to 1:30,000 | 176270 |
| Mulchandani-Bhoj-Conlin syndrome | chr20 | not known | 617352 |
The regions come from Table 1 of the joint statement, which lists each imprinted DMR with its hg38 location, number of CpG sites, imprint origin, associated disorders and type. The expert working groups of the statement based the classification on current knowledge and on DNA from blood, the most frequently used diagnostic tissue. Tissue-specific, transient and polymorphically imprinted loci are not part of the classification. See the paper for details.
The tables were copied from their pages on PubMed Central (Table 2, Table 3). The hg38 starts in Table 1 are already BED starts: they are identical to the Monk et al. regions after lifting from hg19, and no further coordinate shift was applied. All 48 regions were kept. The H19/IGF2 region is listed in Table 1 as one row for the IG-DMR and the TSS-DMR and appears here under the name of the IG-DMR.
Table 1 does not state which parent's allele is methylated. For regions with an oocyte germline origin the maternal allele was taken as methylated, and for regions with a sperm germline origin the paternal allele. For the nine regions that have only a secondary origin, the parent was taken from the Monk et al. 2018 table, which has the same regions. For the 39 other regions both sources agree. The clinical classification comes from Table 3 of the paper. Six regions are not in Table 3: five that Table 1 marks as variable methylation (GPR1-AS:TSS-DMR, VTRNA2-1:DMR, WDR27:Int13-DMR, INPP5F:Int2-DMR, MKRN3:TSS-DMR) are shown as non-clinical, and IGF2:Ex9-DMR, which Table 1 marks as clinically associated, is shown as clinically associated. Two regions that Table 1 marks as clinically associated (IGF2:alt-TSS-DMR and MEG3:TSS-DMR) are listed as non-clinical in Table 3, and the track follows Table 3. The type of Table 1 is kept on the details page for all of them.
The disorder acronyms in Table 1 were expanded using Table 2. Acronyms without a full entry in Table 2 were expanded by interpretation: upd(7)mat is maternal uniparental disomy of chromosome 7, which causes Silver-Russell syndrome, and upd(20)mat is maternal uniparental disomy of chromosome 20, connected here with Mulchandani-Bhoj-Conlin syndrome, the only chromosome 20 syndrome in Table 2. See the makeDoc file and the scripts.
The data can be explored interactively in table format with the Table Browser or the Data Integrator and exported from there to spreadsheet or tab-sep tables. From scripts, the data can be accessed through our API, track=mackay2024Imprint.
For automated download and analysis, the genome annotation is stored in a bigBed file that can be downloaded from our download server. The file for this track is called mackay2024Imprint.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/imprinting/mackay2024/mackay2024Imprint.bb -chrom=chr21 -start=0 -end=100000000 stdout
The original annotation source data can be viewed in Table 1 of the paper.
Mackay DJG, Gazdagh G, Monk D, Brioude F, Giabicani E, Krzyzewska IM, Kalish JM, Maas SM, Kagami M, Beygo J et al. Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis. Clin Epigenetics. 2024 Aug 1;16(1):99. PMID: 39090763; PMC: PMC11295890