Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA313921 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The aim of our study was to characterize the genotypic and phenotypic extent of multi-locus imprinting disturbances. Therefore, we analyzed the DNA methylation pattern of 37 individuals with different DNA methylation disturbances. Of these 37 individuals 17 were previously diagnosed with a multi-locus methylation disturbance (MLID) and the remaing 20 were diagnosed with a typical single locus imprinting disorder (SLID). We compared the DNA methylation of these 37 individuals to the DNA methylation of 38 evaluable individuals born small for gestational age. Our analysis revealed 21/37 individuals with a multi-locus methylation disturbances, characterzied by an aberrant DNA methylation in more than one imprintend gene region. Validation analyses were performed by bisulfite-pyrosequencing in the two imprinted gene regions ZDBF2 and FAM50B. Our analyses revealed each one patient previously diagnosed with Temple- and Angelman syndrome to have MLID. Furthermore, we showed that many of the aberrantly methylated imprinted gene regions in patients with MLID are not associated with the so far known typical imprinting disorders.
2016-12-31 | GSE78773 | GEO
Project description:Phenotypic spectrum and extent of DNA methylation defects associated with multi-locus imprinting disturbances
| PRJNA314498 | ENA
Project description:Uncovering the phenotypic consequences of multi-locus imprinting disturbances using genome-wide methylation analysis in genomic imprinting disorders
| PRJNA995541 | ENA
Project description:Multi-locus imprinting Disturbances (MLID) are methylation defects affecting germline-derived Differentially Methylated Regions (gDMRs) and they have been associated with maternal-effect variants causing imprinting disorders in the offspring. In a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child without any features of imprinting disorders, novel compound heterozygous variants in the NLRP5 gene of the mother were found. Locus-specific and whole-genome methylation analysis by using Infinium MethylationEPIC BeadChip (WG-317-1001, Illumina) revealed MLID with different methylation profiles in both the siblings. The proband and the normal sibling were found to cluster with other MLID cases as shown by principal component analysis and unsupervised hierarchical clustering and remain distinct from controls. However, we were unable to cluster MLID cases associated with specific clinical phenotypes. The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID add further evidence to the role of NLRP5 in the maintenance of genomic imprinting in early embryos. Furthermore, our results demonstrate that within these pedigrees MLID can also be present in the progeny with healthy phenotype, indicating that some sort of compensation occurs between altered imprinted loci in these individuals.
2019-10-01 | GSE133774 | GEO
Project description:Multi-locus imprinting disturbances in a family harboring a ZFP57 truncation
| PRJNA629286 | ENA
Project description:PADI6 is a component of the subcortical maternal complex (SCMC) which is a group of proteins that are abundantly expressed in the oocyte cytoplasm and essential for the proper development of the early embryo. The mutation(s) in the components of the subcortical maternal complex have been associated with reproductive failures, including formation of hydatidiform mole, female infertility and imprinting disorders with multi-locus imprinting disturbance (MLIDs).In the current study by using whole-exome sequencing analysis, we identified four cases of Beckwith-Wiedemann Syndrome with multi-locus imprinting disturbance while their mothers were carriers of variants in PADI6 gene. Genome-wide methylation profiling using Methylation EPIC array depicted the loss of methylation specifically at several known imprinted loci in affected individuals as compared to healthy siblings, parents and controls. Our findings firmly establish the role of PADI6 in imprinting disorders.
2020-10-02 | GSE153211 | GEO
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:Maternal inactivation of genes encoding components of the sub-cortical maternal complex (SCMC) and its associated member PADI6 generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multi-locus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. We generated a mouse line carrying a Padi6 missense variant that was identified in a family with Beckwith-Wiedemann syndrome and MLID. If homozygous in female mice this variant resulted in interruption of embryo development at the 2-cell stage. Single-cell multi-omic analyses demonstrated defective maturation of Padi6-mutant oocytes and incomplete DNA demethylation, down-regulation of zygotic genome activation (ZGA) genes, up-regulation of maternal decay genes and developmental delay in 2-cell embryos developing from Padi6-mutant oocytes, but little effect on genomic imprinting. Western blotting and immunofluorescence analyses showed reduced level of UHRF1 in oocytes and abnormal localization of DNMT1 and UHRF1 in both oocytes and zygotes. Treatment with 5-azacytidine reverted DNA hypermethylation but did not rescue the developmental arrest of mutant embryos. Taken together, this study demonstrates that PADI6 controls both nuclear and cytoplasmic oocyte processes that are necessary for pre-implantation epigenetic reprogramming and ZGA.
2023-10-18 | GSE245424 | GEO
Project description:Maternal inactivation of genes encoding components of the sub-cortical maternal complex (SCMC) and its associated member PADI6 generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multi-locus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. We generated a mouse line carrying a Padi6 missense variant that was identified in a family with Beckwith-Wiedemann syndrome and MLID. If homozygous in female mice this variant resulted in interruption of embryo development at the 2-cell stage. Single-cell multi-omic analyses demonstrated defective maturation of Padi6-mutant oocytes and incomplete DNA demethylation, down-regulation of zygotic genome activation (ZGA) genes, up-regulation of maternal decay genes and developmental delay in 2-cell embryos developing from Padi6-mutant oocytes, but little effect on genomic imprinting. Western blotting and immunofluorescence analyses showed reduced level of UHRF1 in oocytes and abnormal localization of DNMT1 and UHRF1 in both oocytes and zygotes. Treatment with 5-azacytidine reverted DNA hypermethylation but did not rescue the developmental arrest of mutant embryos. Taken together, this study demonstrates that PADI6 controls both nuclear and cytoplasmic oocyte processes that are necessary for pre-implantation epigenetic reprogramming and ZGA.
2023-10-18 | GSE245425 | GEO
Project description:Maternal inactivation of genes encoding components of the sub-cortical maternal complex (SCMC) and its associated member PADI6 generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multi-locus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. We generated a mouse line carrying a Padi6 missense variant that was identified in a family with Beckwith-Wiedemann syndrome and MLID. If homozygous in female mice this variant resulted in interruption of embryo development at the 2-cell stage. Single-cell multi-omic analyses demonstrated defective maturation of Padi6-mutant oocytes and incomplete DNA demethylation, down-regulation of zygotic genome activation (ZGA) genes, up-regulation of maternal decay genes and developmental delay in 2-cell embryos developing from Padi6-mutant oocytes, but little effect on genomic imprinting. Western blotting and immunofluorescence analyses showed reduced level of UHRF1 in oocytes and abnormal localization of DNMT1 and UHRF1 in both oocytes and zygotes. Treatment with 5-azacytidine reverted DNA hypermethylation but did not rescue the developmental arrest of mutant embryos. Taken together, this study demonstrates that PADI6 controls both nuclear and cytoplasmic oocyte processes that are necessary for pre-implantation epigenetic reprogramming and ZGA.
2023-10-18 | GSE245423 | GEO