Methylation analysis for plasma DNA of patients with organ transplantation
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ABSTRACT:
PROVIDER: EGAS00001004788 | EGA |
REPOSITORIES: EGA
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Project description:We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues.
| EGAD00001007041 | EGA
Project description:<p><b>Background</b>: Circulating cell free (ccf) fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the genetically distinct maternal and fetal DNA. Current testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA and thus support additional clinical opportunities; however, this depends on knowledge of the methylomes of ccf DNA and its cellular contributors.</p> <p><b>Results</b>: Whole genome bisulfite sequencing was performed on a set of unmatched samples including ccf DNA from 8 non-pregnant (NP) and 7 pregnant female donors and genomic DNA from 7 buffy coat and 5 placenta samples. We found CpG cytosines within longer fragments were more likely to be methylated, linking DNA methylation and fragment size in ccf DNA. Comparison of the methylomes of placenta and NP ccf DNA revealed many of the 51,259 identified differentially methylated regions (DMRs) were located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases, regions we termed placenta hypomethylated domains. DMRs identified when comparing placenta to NP ccf DNA were recapitulated in pregnant ccf DNA, confirming the ability to detect differential methylation in ccf DNA mixtures.</p> <p><b>Conclusions</b>: We generated methylome maps for four sample types at single base resolution, identified a link between DNA methylation and fragment length in ccf DNA, identified DMRs between sample groups, and uncovered the presence of megabase-size placenta hypomethylated domains. Furthermore, we anticipate these results to provide a foundation to which future studies using discriminatory DNA methylation may be compared.</p>
| phs000846 | dbGaP
Project description:Leucyl and cystinyl aminopeptidase (LNPEP/oxytocinase) is a key regulator of oxytocin. Our objectives were to measure serum concentrations of LNPEP and determine the presence of LNPEP and oxytocin (OXT) in equine tissue. LNPEP was measured by ELISA in serum obtained: every other day from ovulation (D0) until D21-22 in nonpregnant and pregnant mares; and at around 320 days of gestation, at 24 hours before foaling, and 20 min and 2 hrs post-foaling. Placenta from the pregnant horn (PH), nonpregnant horn (NPH) and body (B) and from tissues of 6 nonpregnant mares were homogenized and extracts obtained for protein determination and LNPEP ELISA assay. Identification of LNPEP and OXT protein in tissues was also performed via western blot (WB), immunohistochemistry (IHC) and liquid chromatography-mass spectrometry (LC-MS/MS). Furthermore, in situ hybridization was performed for LNPEP and OXT on endometrium, myometrium, pituitary and corpus luteum (CL). No difference in serum LNPEP concentration was identified between any of the groups. The NPH had the lowest quantities of LNPEP (P<0.05). The highest to lowest LNPEP U/mg protein by tissue were: myometrium> follicle wall> endometrium> kidney>CL> liver. Oxytocin was identified in the equine pituitary, CL and placenta. LNPEP may regulate the availability of luteal OXT locally.
2023-05-10 | PXD036368 | Pride
Project description:We used bulk RNA sequencing to investigate the molecular signature of total tissue isolated from AD patients carrying APOE ε3/ε3 and APOEε3/ε4 alleles.
2023-07-31 | GSE234488 | GEO
Project description:In this study we performed RNA sequencing to determine and compare the transcriptome of regulatory T cells (Tregs) present in the thymus, placenta, spleen and white adipose tissue (FAT) of pregnant mice. We further assessed how the expression of the receptor Rank in the thymic medullary epithelia affects the transcriptional program of these Treg populations. For the isolation of viable and bona fide Tregs, we first generated RankWt (wild type control mice) and RankΔFoxn1 (which lack expression of Rank in the thymic epithelia) and further crossed them to mice that express GFP from the Foxp3 promoter. Neuropilin1 was used to mark the thymic origin of the Tregs. Equal numbers of Tregs (280 cells) were sorted as CD45-CD8-CD4+GFP+Neuropilin1High cells from the thymus and placenta of RankWtFoxp3GFP/GFP and RankΔFoxn1Foxp3GFP/GFP pregnant females at E17.5 (both samples from the same female; n=4 females per genotype). Thymus Tregs from non-pregnant littermate female mice for each genotype cohort were also studied. To increase robustness, the 280 placental Tregs were purified from 5 individual placentas per pregnant female (56 Tregs/placenta). Our study is the first one to determine the transcriptome of thymus and placenta Tregs during pregnancy and reveals that, partially dependent on Rank expression in the thymic epithelia, placental-resident Tregs are molecularly distinct from thymic Tregs. In a separate experiment with different pregnant mice than those used for thymus and placenta analysis, VAT Tregs (20-30 cells) and splenic Tregs (150 cells) were sorted (both samples from the same female) by using the same mouse lines (Rank Wt and RankΔFoxn1), embryological days of analysis (E17.5) and sorting strategies.
2020-10-21 | GSE97666 | GEO
Project description:The Repressor Element-1 Silencing Transcription (REST) factor is a transcriptional repressor. The aim of this study is to characterize role of REST in placental influences on offspring brain. REST was ablated in mouse placenta by mating mouse carrying floxed (FL) alleles of REST with mouse that expresses Cre recombinase under the control of the promoter of placenta-specific gene Gcm1 (glial cells missing 1). To investigate placental influence on gene expression of adult offspring brain cells, single-nuclei RNA-seq was performed. Data analysis showed that ablation of placental REST significantly impacted specific pathways in choroid plexus and ependymal cells of the offspring brain.
2024-04-19 | GSE237181 | GEO
Project description:Objective: To explore the characteristics and underlying molecular mechanisms of genome-scale expression profiles of women with- or without- GDM and their offspring. Materials and Methods: We recruited a group of 21 pregnant women with GDM and 20 healthy pregnant women as controls. For each pregnant women, RNA-seq were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially expressed genes (DEGs) were identified with BMI of pregnant women as covariates. Then, functional enrichment analysis was performed separately or interactively in placenta and umbilical cord blood. Results: Through the comparison of GDM and healthy samples, 1442 and 488 DEGs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta expression profiles of GDM women mirrored the molecular characteristics of type II diabetes and insulin resistance patients. DEGs illustrated significant overlaps among placenta and umbilical cord blood samples, and the overlapping DEGs were associated with endocrine resistance and insulin resistance. Conclusions: Our research demonstrated the transcriptomic alternations of GDM mothers and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
2022-05-31 | GSE203346 | GEO
Project description:Given the possible critical importance of placental gene imprinting and random monoallelic expression on fetal and infant health, most of those genes must be identified, in order to understand the risks that the baby might meet during pregnancy and after birth. Therefore, the aim of the current study was to introduce a workflow and tools for analyzing imprinted and random monoallelic gene expression in human placenta, by applying whole-transcriptome (WT) RNA sequencing of placental tissue and genotyping of coding DNA variants in family trios. Ten family trios, each with a healthy spontaneous single-term pregnancy, were recruited. Total RNA was extracted for WT analysis, providing the full sequence information for the placental transcriptome. Parental and child blood DNA genotypes were analyzed by exome SNP genotyping microarrays, mapping the inheritance and estimating the abundance of parental expressed alleles. Imprinted genes showed consistent expression from either parental allele, as demonstrated by the SNP content of sequenced transcripts, while monoallelically expressed genes had random activity of parental alleles. We revealed 4 novel possible imprinted genes (LGALS8, LGALS14, PAPPA2 and SPTLC3) and confirmed the imprinting of 4 genes (AIM1, PEG10, RHOBTB3 and ZFAT-AS1) in human placenta. The major finding was the identification of 4 genes (ABP1, BCLAF1, IFI30 and ZFAT) with random allelic bias, expressing one of the parental alleles preferentially. The main functions of the imprinted and monoallelically expressed genes included: i) mediating cellular apoptosis and tissue development; ii) regulating inflammation and immune system; iii) facilitating metabolic processes; and iv) regulating cell cycle. Placentas from ten family trios were analysed using RNA-Seq.
2014-09-01 | E-GEOD-56524 | biostudies-arrayexpress
Project description:Previous work has suggested that the imprinted gene Phlda2 regulates the signalling function of the placenta by modulating the size of the endocrine compartment. This study investigated the affect that Phlda2 mutant placenta has upon the brains of the wildtype dams carrying different placenta and consequently offspring. Affymetrix Mouse Microarray analysis of maternal hippocampus and hypothalamus was used to demonstrate gene expression changes in the maternal brains of wildtype dams carrying mutant placenta at E16.5.
2018-06-06 | GSE115276 | GEO
Project description:In the yeast saccharoryces cerevisiae, RPA49 full-deletion mutants show a strong growth defect at 30°C and are unable to grow at 25°C. However, spontaneous suppressors that restore growth at 25°C are observed. We attend to identified new suppressor alleles after UV treatment. To mapped the genomic location of suppressor allele we have used a derivative of the so called \\"Genetic Interaction Mapping\\" (GIM) method (Decourty et al, 2008). Briefly, we have mated a yeast strain carrying the deletion of rpa49 and the a suppressor allele (query strain) with the pool of all haploid deletion mutants from the Euroscarf yeast gene deletion project. All deletions in strains from the Euroscarf collection are flanked by 2 unique 20 bases pair DNA tag (so-called Up-Tag and DN-tag) that allow detection on oligonucleotide micro-array. After sporulation in mass, spores carrying the rpa49 deletion, the suppressor allele and euroscarf deleted genes were selected and grow in a competition culture for 10 generations. As selected spores result from genetic re-association of allele from tested strains and euroscarf strain, all strains carrying a deleted genes from the euroscarf collection that is genetically link to the suppressor allele will be depleted in the culture. We next extract genomic DNA , amplified and labelled the tags. The relative quantity of each deletion tags in experiments with strain carrying suppressor alleles were estimated in a two color array experiment relative to the quantity of the tags in parallel experiments using two different wild-type strains.
2019-12-31 | E-MTAB-7831 | biostudies-arrayexpress