Apart from the cardinal loci, the pipeline also detected additional significantly hypomethylated loci, including but not limited to those identified by targeted testing.
For example, in TND-MLMD patients both CH and Weisberg t-tests were able to identify a number of sites including the cardinal disease locus PLAGL1 in all patients.
In addition to the samples with MLMD, we analysed samples from patients with 'simple' imprinting disorders where targeted testing indicated that hypomethylation was restricted to the cardinal disease locus.
Likewise, the CH and Weisberg t-tests produced similar results for BWS-MLMD patients, identifying several regions of differential methylation, including the cardinal disease locus KCNQ1OT1, whereas the one-sample t-test again detected many false positive sites as significant differential methylation.
In this study, we additionally included four TND and three BWS patients where targeted testing detected DNA hypomethylation only at the cardinal disease loci, with no known involvement of any other imprinted locus (denoted 'simple' BWS and TND cases).
Previous targeted testing of our samples identified several known regions of biologically significant differential methylation in addition to the cardinal disease loci.
In all patients, the cardinal disease loci were identified: that is, PLAGL1 in TND-MLMD patients and KCNQ1OT1 in BWS patients.
Cardinal Dolan supports the trade.
The results confirmed that this complex is affected in Parkinson's disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapid eye movement sleep behaviour disorder.
