Intraindividual rDNA copy number variation and methylation in humans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1263007 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33610600_1.fastq.gz | Fastqsanger.gz | |||
| SRR33610600_2.fastq.gz | Fastqsanger.gz | |||
| SRR33610601_1.fastq.gz | Fastqsanger.gz | |||
| SRR33610601_2.fastq.gz | Fastqsanger.gz | |||
| SRR33610602_1.fastq.gz | Fastqsanger.gz |
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Project description:The absolute number of rDNA transcription units can vary by about one power of ten among individuals. Apart from extensive rDNA copy number (CN) variation and instability in many cancers, there is little information on the extent of intraindividual CN variation between normal s. Here we used droplet digital PCR and deep bisulfite sequencing to determine both the absolute rDNA CN and the number of presumably active CN with a hypomethylated (0-10%) promoter region in up to six different s of 13 autopsy probands. In general, the absolute rDNA CN as well as the frequency of the minor A variant were highly similar between s (cerebellum, cerebrum, colon, heart, intestine, kidney, and liver liver and spleen) of the same individual. However, in some probands absolute CN in one or multiple s was much higher than in the other s., consistent with relaxation/breakdown of the CN control system. The amplified copies were inactivated by promoter methylation and, thus, the number of active CN was largely independent from absolute CN. Collectively, our data suggest that with some notable exceptions absolute and even more active rDNA CN are maintained during development and differentiation in different s of the same individual. Despite the low intraindividual variation active CN appeared to systematically vary between s. Cerebellum, which is characterized by the highest density of non-dividing neuronal cells in the body, consistently exhibited lower active CN than other s. We estimate that a minimum number of > 50 active rDNA TU is required for normal /organ function.
2025-06-16 | GSE297209 | GEO
Project description:Preserving a large number of essential yet highly unstable ribosomal DNA (rDNA) repeats is critical for the germline to perpetuate the genome through generations. Spontaneous rDNA loss must be countered by rDNA copy number (CN) expansion. Germline rDNA CN expansion is best understood in Drosophila melanogaster, which relies on unequal sister chromatid exchange (USCE) initiated by DNA breaks at rDNA. The rDNA-specific retrotransposon R2 responsible for USCE-inducing DNA breaks is typically expressed only when rDNA CN is low to minimize the danger of DNA breaks; however, the underlying mechanism of R2 regulation remains unclear. Here we identify the insulin receptor (InR) as a major repressor of R2 expression, limiting unnecessary R2 activity. Through single-cell RNA sequencing we find that male germline stem cells (GSCs), the major cell type that undergoes rDNA CN expansion, have reduced InR expression when rDNA CN is low. Reduced InR activity in turn leads to R2 expression and CN expansion. We further find that dietary manipulation alters R2 expression and rDNA CN expansion activity. This work reveals that the insulin pathway integrates rDNA CN surveying with environmental sensing, revealing a potential mechanism by which diet exerts heritable changes to genomic content.
2024-12-02 | GSE263351 | GEO
Project description:We have performed a genome wide analysis of gene copy number polymorphisms and report here for the first time that the human genome contains thousands of well-characterized genes at copy numbers different from one maternal and one paternal allele; and that, furthermore, the copy numbers of hundreds of well-characterized genes can vary between two normal healthy humans making this a major source of genetic variation. Groups of genes affected by CNPs include genes involved in signal transduction, oncogenesis, cell adhesion activity and several types of immune response. In contrast to SNPs, which preferentially affect non-coding regions of the genome, copy number polymorphisms of well-characterized and actively expressed genes are very likely to have important biological consequences. Keywords: Gene Copy Number Variation
2006-07-01 | GSE4981 | GEO
Project description:Intraindividual copy number variations (CNVs) happen post-zygotically, however their origin is largely unknown. They might appear either through aging or may resist following the common chromosome instability at the preimplantation stage. To uncover a part of this question we investigated fetal mosaicism and its origin. According to distribution pattern of frequent CNVs in derivatives of different germ layers, their origin is early development including preimplantation, whereas CNVs with low frequency occur in later stages. Both fetuses share CNVs, some in the same tissues and some other in different tissues. Functional analysis showed that altered genes were involved in embryonic development pathways. Each organ inherits CNVs with an unpredictable pattern due to extensive cell mixing/migration in embryonic development. Since we have found frequent intraindividual reciprocal CNVs as events with preimplantation origin in both fetuses, mosaic embryo transfer should be performed with caution because it may increase susceptibility to develop early/late onset diseases with genetic component even though recent reports seems to encourage IVF clinics for mosaic embryo transfer.
2020-09-25 | GSE104314 | GEO
Project description:Great Ape Copy Number Variation
| PRJNA144461 | ENA
Project description:Ribosome is the most abundant RNA-protein complex in a cell and many copies of the ribosomal RNA gene (rDNA) have to be maintained. However, arrays of tandemly repeated rDNA genes can lose the copies by intra-repeat recombination. Loss of the rDNA copies of Saccharomyces cerevisiae is counteracted by gene amplification whereby the number of rDNA repeats stabilizes around 150 copies, suggesting the presence of a monitoring mechanism that counts and adjusts the number. Here, we report that in response to rDNA copy loss, the upstream activating factor (UAF) for RNA polymerase I which transcribes the rDNA is released and directly bind to a RNA polymerase II transcribed gene, SIR2 to repress, whose gene products silence rDNA recombination. We show that the amount of UAF determines rDNA copies number that is stably maintained. UAF ensures rDNA production not only by rDNA transcription activation but also by its copy number maintenance.
2019-01-03 | GSE116661 | GEO
Project description:The human tRNAome consists of more than 500 interspersed tRNA genes comprising 51 anticodon families of largely unequal copy number. We examined tRNA gene copy number variation (tgCNV) in six individuals; two kindreds of two parents and a child, using high coverage whole genome sequence data. Such differences may be important because translation of some mRNAs is sensitive to the relative amounts of tRNAs and because tRNA competition determines translational efficiency vs. fidelity and production of native vs. misfolded proteins. We identified several tRNA gene clusters with CNV, which in some cases were part of larger iterations. In addition there was an isolated tRNALysCUU gene that was absent as a homozygous deletion in one of the parents. When assessed by semiquantitative PCR in 98 DNA samples representing a wide variety of ethnicities, this allele was found deleted in hetero- or homozygosity in all groups at ~50% frequency. This is the first report of copy number variation of human tRNA genes. We conclude that tgCNV exists at significant levels among individual humans and discuss the results in terms of genetic diversity and prior genome wide association studies (GWAS) that suggest the importance of the ratio of tRNALys isoacceptors in Type-2 diabetes.
| S-EPMC3941035 | biostudies-literature
Project description:Copy-number variants (CNVs) are large-scale amplifications or deletions of DNA that can drive rapid adaptive evolution and result in large-scale changes in gene expression. Whereas alterations in the copy number of one or more genes within a CNV can confer a selective advantage, other genes within a CNV can decrease fitness when their dosage is changed. Dosage compensation - in which the gene expression output from multiple gene copies is less than expected - is one means by which an organism can mitigate the fitness costs of deleterious gene amplification. Previous research has shown evidence for dosage compensation at both the transcriptional level and at the level of protein expression; however, the extent of compensation differs substantially between genes, strains, and studies. Here, we investigated sources of dosage compensation at multiple levels of gene expression regulation by defining the transcriptome, translatome and proteome of experimentally evolved yeast (Saccharomyces cerevisiae) strains containing adaptive CNVs.
2023-11-01 | PXD046587 | Pride