Beckwith-Wiedemann syndrome and large offspring syndrome involve alterations in methylome, transcriptome, and chromatin configuration
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ABSTRACT:
ORGANISM(S): Bos indicus x Bos taurus
PROVIDER: GSE251961 | GEO | 2025/11/25
REPOSITORIES: GEO
Similar Datasets
Project description:Beckwith-Wiedemann Syndrome (BWS) is the most common epigenetic overgrowth syndrome, caused by epigenetic alterations on chromosome 11p15. In ~50% of patients with BWS, the imprinted region KvDMR1 (IC2) is hypomethylated. Nearly all children with BWS develop organ overgrowth and up to 28% develop cancer during childhood. The global epigenetic alterations beyond the 11p15 region in BWS are not currently known. Uncovering these alterations at the methylome, transcriptome, and chromatin architecture levels are necessary steps to improve the diagnosis and understanding of patients with BWS. Here we characterized the complete epigenetic profiles of BWS IC2 individuals together with the animal model of BWS, bovine large offspring syndrome (LOS). A novel finding of this research is the identification of two molecular subgroups of BWS IC2 individuals. Genome-wide alterations were detected for DNA methylation, transcript abundance, alternative splicing events of RNA, chromosome compartments, and topologically associating domains (TADs) in BWS and LOS, with shared alterations identified between species. Altered chromosome compartments and TADs were correlated with differentially expressed genes in BWS and LOS. Together, we highlight genes and genomic regions that have the potential to serve as targets for biomarker development to improve current molecular diagnostic methodologies for BWS.
2025-11-25 | GSE251959 | GEO
Project description:Beckwith-Wiedemann Syndrome (BWS) is the most common epigenetic overgrowth syndrome, caused by epigenetic alterations on chromosome 11p15. In ~50% of patients with BWS, the imprinted region KvDMR1 (IC2) is hypomethylated. Nearly all children with BWS develop organ overgrowth and up to 28% develop cancer during childhood. The global epigenetic alterations beyond the 11p15 region in BWS are not currently known. Uncovering these alterations at the methylome, transcriptome, and chromatin architecture levels are necessary steps to improve the diagnosis and understanding of patients with BWS. Here we characterized the complete epigenetic profiles of BWS IC2 individuals together with the animal model of BWS, bovine large offspring syndrome (LOS). A novel finding of this research is the identification of two molecular subgroups of BWS IC2 individuals. Genome-wide alterations were detected for DNA methylation, transcript abundance, alternative splicing events of RNA, chromosome compartments, and topologically associating domains (TADs) in BWS and LOS, with shared alterations identified between species. Altered chromosome compartments and TADs were correlated with differentially expressed genes in BWS and LOS. Together, we highlight genes and genomic regions that have the potential to serve as targets for biomarker development to improve current molecular diagnostic methodologies for BWS.
2025-11-25 | GSE251960 | GEO
Project description:Beckwith-Wiedemann Syndrome (BWS) is the most common epigenetic overgrowth syndrome, caused by epigenetic alterations on chromosome 11p15. In ~50% of patients with BWS, the imprinted region KvDMR1 (IC2) is hypomethylated. Nearly all children with BWS develop organ overgrowth and up to 28% develop cancer during childhood. The global epigenetic alterations beyond the 11p15 region in BWS are not currently known. Uncovering these alterations at the methylome, transcriptome, and chromatin architecture levels are necessary steps to improve the diagnosis and understanding of patients with BWS. Here we characterized the complete epigenetic profiles of BWS IC2 individuals together with the animal model of BWS, bovine large offspring syndrome (LOS). A novel finding of this research is the identification of two molecular subgroups of BWS IC2 individuals. Genome-wide alterations were detected for DNA methylation, transcript abundance, alternative splicing events of RNA, chromosome compartments, and topologically associating domains (TADs) in BWS and LOS, with shared alterations identified between species. Altered chromosome compartments and TADs were correlated with differentially expressed genes in BWS and LOS. Together, we highlight genes and genomic regions that have the potential to serve as targets for biomarker development to improve current molecular diagnostic methodologies for BWS.
2025-12-09 | GSE313083 | GEO
Project description:Beckwith-Wiedemann syndrome and large offspring syndrome involve alterations in methylome, transcriptome, and chromatin configuration
| PRJNA1056026 | ENA
Project description:Beckwith-Wiedemann syndrome and large offspring syndrome involve alterations in methylome, transcriptome, and chromatin configuration [WGBS]
| PRJNA1056034 | ENA
Project description:Beckwith-Wiedemann syndrome and large offspring syndrome involve alterations in methylome, transcriptome, and chromatin configuration [RNA-Seq]
| PRJNA1056033 | ENA
Project description:The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS.
| S-EPMC6691986 | biostudies-literature
Project description:The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS.
2019-07-30 | GSE117015 | GEO
Project description:Beckwith-Wiedemann syndrome (BWS) is a human loss-of-imprinting syndrome primarily characterized by macrosomia, macroglossia, and abdominal wall defects. BWS has been associated with misregulation of two clusters of imprinted genes. Children conceived with the use of assisted reproductive technologies (ART) appear to have an increased incidence of BWS. As in humans, ART can also induce a similar overgrowth syndrome in ruminants which is referred to as large offspring syndrome (LOS). The main goal of our study is to determine if LOS shows similar loss-of-imprinting at loci known to be misregulated in BWS. To test this, Bos taurus indicus × Bos taurus taurus F1 hybrids were generated by artificial insemination (AI; control) or by ART. Seven of the 27 conceptuses in the ART group were in the > 97th percentile body weight when compared with controls. Further, other characteristics reported in BWS were observed in the ART group, such as large tongue, umbilical hernia, and ear malformations. KCNQ1OT1 (the most-often misregulated imprinted gene in BWS) was biallelically-expressed in various organs in two out of seven overgrown conceptuses from the ART group, but shows monoallelic expression in all tissues of the AI conceptuses. Furthermore, biallelic expression of KCNQ1OT1 is associated with loss of methylation at the KvDMR1 on the maternal allele and with downregulation of the maternally-expressed gene CDKN1C. In conclusion, our results show phenotypic and epigenetic similarities between LOS and BWS, and we propose the use of LOS as an animal model to investigate the etiology of BWS.
| S-EPMC3857339 | biostudies-literature
Project description:Beckwith-Wiedemann syndrome (BWS) is a model disorder for the study of imprinting, growth dysregulation, and tumorigenesis. Unique observations in this disorder point to an important embryonic developmental window relevant to the observations of increased monozygotic twinning and an increased rate of epigenetic errors after subfertility/assisted reproduction.
| S-EPMC2987155 | biostudies-other