Chromosome X Mosaicism Methylation Study
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA320447 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:<p>This study investigates methylation patterns in promoter regions on the X chromosomes of females with X chromosome mosaicism in an effort to phase mosaic events to either the active or inactive X chromosome.</p>
| phs001112 | dbGaP
Project description:Human development relies on the correct replication, maintenance and segregation of our genetic blueprints. How these processes are monitored across embryonic lineages, and why genomic mosaicism varies during development remain unknown. Using pluripotent stem cells, we identify that several patterning signals –including WNT, BMP and FGF– converge into the modulation of DNA replication stress and damage during S-phase, which in turn controls chromosome segregation fidelity in mitosis. We show that the WNT and BMP signals protect from excessive origin firing, DNA damage and chromosome missegregation derived from stalled forks in pluripotency. Cell signalling control of chromosome segregation declines during lineage specification into the three germ layers, but re-emerges in neural progenitors. In particular, we find that the neurogenic factor FGF2 induces DNA replication stress-mediated chromosome missegregation during the onset of neurogenesis, which could provide a rationale for the elevated chromosomal mosaicism of the developing brain. Our results highlight roles for morphogens and cellular identity in genome maintenance that contribute to somatic mosaicism during mammalian development.
2024-07-31 | PXD054388 | Pride
Project description:Constitutional MLH1 epimutations are a rare cause of Lynch syndrome. Low methylation levels (≤10%) have been occasionally described. The aim of this study was the identification of patients with low levels of epigenetic mosaicism in MLH1 gene. Eighteen patients with MLH1 hypermethylated tumors and undetectable methylation in blood as assessed by Methylation-Specific Multiplex Ligation-Dependent Probe Amplification were included (MS-MLPA). Highly sensitive MS-Melting Curve Analysis (MS-MCA) at MLH1 promoter was used to screen for epigenetic mosaicism. Constitutional methylation was confirmed by other methods. Mutational analysis of hereditary cancer genes including MLH1 was performed. MS-MCA analysis identified one case (5.6%) with low levels of methylation (1-2%) in blood DNA. The patient had developed 3 gastrointestinal tumors at ages 22, 24 and 25, sharing MLH1 promoter hypermethylation and loss of heterozygosity associated with c.655A allele. The presence of low MLH1 methylation levels was confirmed by clonal bisulfite sequencing, evidencing the association with c.-93G allele (in phase with c.655G). The extension of the hypermethylated region overlaps with the reported in constitutional MLH1 epimutation carriers. No rare germline variants were identified. The use of highly sensitive techniques such as MS-MCA has demonstrated to be useful for the detection of low MLH1 methylation levels in blood.
2019-05-22 | GSE131541 | GEO
Project description:Model of chromosome mosaicism reveals normal development of chimeric mammalian embryos
| PRJEB12768 | ENA
Project description:To increase our understanding of epigenetic patterns associated with aneuploidy we used constitutional trisomy 8 mosaicism as a model, enabling analyses of single cell clones, harboring either trisomy or disomy 8, from the same patient. We profiled gene and miRNA expression as well as genome-wide and promoter specific DNA methylation and hydroxymethylation patterns in trisomic and disomic fibroblasts, using microarrays and methylated DNA immunoprecipitation.
2012-12-01 | GSE40317 | GEO
Project description:To increase our understanding of epigenetic patterns associated with aneuploidy we used constitutional trisomy 8 mosaicism as a model, enabling analyses of single cell clones, harboring either trisomy or disomy 8, from the same patient. We profiled gene and miRNA expression as well as genome-wide and promoter specific DNA methylation and hydroxymethylation patterns in trisomic and disomic fibroblasts, using microarrays and methylated DNA immunoprecipitation. comparison of trisomy 8 cells with disomic as well as reference fibroblasts
2012-12-01 | E-GEOD-40317 | biostudies-arrayexpress
Project description:To increase our understanding of epigenetic patterns associated with aneuploidy we used constitutional trisomy 8 mosaicism as a model, enabling analyses of single cell clones, harboring either trisomy or disomy 8, from the same patient. We profiled gene and miRNA expression as well as genome-wide and promoter specific DNA methylation and hydroxymethylation patterns in trisomic and disomic fibroblasts, using microarrays and methylated DNA immunoprecipitation.
2012-12-01 | GSE40319 | GEO
Project description:Many studies estimate that chromosomal mosaicism within the cleavage stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism is overestimated due to technical inconsistency rather than biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques.Thirteen arrested cleavage stage embryos were studied. Each was biopsied into individual cells (n=160). The cells from each embryo were randomized into two groups. Those destined for FISH based aneuploidy screening (n=75) were fixed, 1 cell per slide. Cells for SNP microarray based aneuploidy screening (n=85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P=0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (4 of 13 embryos; 31%) than by FISH (13 of 13 embryos; 100%)(P=0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2+0.2) than microarray (1.3+0.2)(P<0.0001). This is the first prospective, randomized, blinded, and paired comparison between microarray and FISH based aneuploidy screening. Aneuploidy and mosaicism were less common with microarray. While evaluating a smaller number of chromosomes with a proportionally smaller opportunity for finding mosaicism, FISH still had a dramatically higher level of inter-cell variation in diagnosis. SNP microarray based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH.
2010-05-19 | GSE20975 | GEO