Random monoallelic expression in the mouse: SNP array data
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE35678 | GEO | 2012/02/10
SECONDARY ACCESSION(S): PRJNA152401
REPOSITORIES: GEO
Similar Datasets
Project description:Random monoallelic expression is defined by the allele-specific expression of genes, and by the fact that for an individual cell this monoallelic expression is neither obligate nor necessarily coordinated with the allelic expression in other cells. In order to find novel examples of random monoallelic expression in mouse, we did a transcriptome-wide survey of allele-specific gene expression in two different immortalized cell types. Lymphoblast cell lines and fibroblast cell lines were established (both clonal and nonclonal) and were used as a source of both nuclear RNA and genomic DNA. These samples were assessed for allele-specific gene expression using a custom-designed Mouse SNP Chip. A large number of genes (over 10% of those that were assessed in lymphoblast clones) displayed random monoallelic expression. For each cell line, two replicate samples of ds-cDNA were assessed for monoallelic expression, while genomic DNA was assessed as a control for possible LOH events. Nonclonal samples were used as controls for cis-acting allelic bias.
2012-02-10 | E-GEOD-35678 | biostudies-arrayexpress
Project description:X-chromosome inactivation (XCI) in females and allelic exclusion of olfactory receptor or immunoglobulin loci, represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation and once established, the monoallelic state can be highly stable. We show that monoallelic expression also occurs in vivo, in the absence of DNA sequence polymorphism, similarly to XCI. Several of the genes identified play important roles in development and have also been implicated in human autosomal dominant disorders. We propose that monoallelic expression of such genes contributes to the fine-tuning of the developmental regulatory pathways they control and in the context of a mutation, RME can predispose to loss of function in a proportion of cells and thus contribute to disease.
2014-02-27 | GSE54016 | GEO
Project description:The goal of this experiment is to identify autosomal random monoallelic gene in ESC and NPC from a C57BL6J x CAST hybrid
2014-02-26 | E-MTAB-1822 | biostudies-arrayexpress
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: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.
2014-09-01 | GSE56685 | 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.
2014-09-01 | GSE56524 | GEO
Project description:In the diploid genome, genes come in two copies, which can have different DNA sequence and where one is maternal and one is paternal. In a particular cell, a gene could potentially be expressed from both copies (biallelic expression) or only one (monoallelic). We performed RNA-Sequencing on individual cells, from zygote to the cells of the late blastocyst, and also individual cells from the adult liver. Using first generation crosses between two distantly related mouse strains, CAST/Ei and C57BL/6, we determined the expression separately from the maternal and paternal alleles. We found that half of the genes were expressed by only one allele, randomly so that some cells would express the paternal allele, some the maternal and a few cell both alleles. We also observed the spread of the progressive inactivation of the paternal X chromosome. First generation mouse strain crosses were used to study monoallelic expression on the single cell level
2014-01-10 | E-GEOD-45719 | biostudies-arrayexpress
Project description:Binary outcomes of enhancer activity underlie stable random monoallelic expression
| PRJNA751043 | ENA
Project description:X-chromosome inactivation (XCI) in females and allelic exclusion of olfactory receptor or immunoglobulin loci, represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation and once established, the monoallelic state can be highly stable. We show that monoallelic expression also occurs in vivo, in the absence of DNA sequence polymorphism, similarly to XCI. Several of the genes identified play important roles in development and have also been implicated in human autosomal dominant disorders. We propose that monoallelic expression of such genes contributes to the fine-tuning of the developmental regulatory pathways they control and in the context of a mutation, RME can predispose to loss of function in a proportion of cells and thus contribute to disease. The hybrid mouse ES cell lines F1-21.6 and F1-23 (129Sv-Cast/EiJ), previously described in (Luikenhuis et al., 2001) and (Jonkers et al., 2009), were grown on mitomycin C-inactivated MEFs in ES cell media containing 15% FBS (Gibco), 10-4 M b-mercaptoethanol (Sigma), 1000U/ml of leukaemia inhibitory factor (LIF, Chemicon). Mouse ES cells were differentiated into neural progenitor cells (NPC) as previously described (Conti et al., 2005; Splinter et al., 2011). Total RNAs were prepared from the mouse ES cell lines, 4 NPC clones derived from ES cell line F1-21.6 plus one replicate, and 4 NPC clones derived from ES cell line F1-23 plus one replicate. Library preparation after polyadenylated RNA purification was performed according to the standard Illumina instructions. Paired-end 100bp reads were generated using the HiSeq 2000 sequencing platform.
2014-02-27 | E-GEOD-54016 | biostudies-arrayexpress
Project description:In mammalian cells, large groups of genes show epigenetically controlled unequal transcription of maternal and paternal alleles. Thousands of autosomal genes subject to monoallelic expression (MAE) comprise the largest such group. The initial random allelic choice in these loci is followed by mitotically stable transmission of the allele-specific state, leading to stable epigenetic and functional differences between clonal cell lineages. Molecular mechanisms underpinning MAE maintenance are not known. We devised and performed a drug screen for reactivation of epigenetically silenced alleles in mouse cells, using a new strategy based on deep targeted allele-specific RNA sequencing, which can read out multiple loci simultaneously. We found that, contrary to previous observations, DNA methylation plays a key role in mitotic memory of MAE in multiple autosomal loci. Having established that a specific perturbation can affect multiple loci, we assessed genome-wide impact of the drug exposure in several clonal cell lines, identifying over 600 genes with allele-specific expression changing with DNA methylation. We found that multiple distinct states of allele-specific expression correspond to the extent of DNA methylation and can be stably maintained, indicating allelic rheostat role of DNA methylation. Our findings reveal a previously unappreciated interplay of genetic and epigenetic control of allele-specific expression and reinforce the role of such regulation in maintaining differences between developmentally equivalent clonal cell lineages.
2023-09-20 | GSE144006 | GEO