Homo sapiens
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PROVIDER: PRJNA221240 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Somatic mosaicism for copy number variation in differentiated human tissues
| PRJNA103443 | ENA
Project description:Genetic variation is responsible for the generation of phenotypic diversity, including susceptibility to disease. Two major types of variation are known: single nucleotide polymorphisms (SNPs) and a more recently discovered structural variation, involving changes in copy number (CNVs) of kilobase- to megabase-sized chromosomal segments. Variation caused by CNVs has exceeded the amount of SNP-based differences expected to exist between two unrelated humans. Furthermore, many CNVs have been associated with disease predisposition. It is unknown whether CNVs arise in somatic cells, but it is, however, generally assumed that normal cells are genetically identical. Here we show that CNVs are frequent in healthy somatic cells of adult humans. We tested 34 tissue samples from three subjects and, having analyzed for each tissue <10-6 of all cells expected in an adult human, we observed at least six CNVs, affecting a single organ or one or more tissues of the same subject. The CNVs ranged from 82-176 kb, often encompassing known genes, potentially affecting gene function. Our results point to a paradigm shift in the genetics of somatic cells and indicate that humans are commonly affected by somatic mosaicism for stochastic CNVs, which occur in a substantial fraction of cells. A considerable number of phenotypes and diseases affecting humans are a consequence of a somatic process. Thus, our conclusions will be important for the delineation of genetic factors behind these phenotypes. Consequently, biobanks should consider sampling multiple tissues in order to better address mosaicism in the studies of somatic disorders. Furthermore, forensic medicine laboratories should be sensitized to the issue of underestimated frequency of somatic CNV mosaicism. Keywords: copy number variation (CNV), phenotype diversity, somatic cells
2008-09-16 | GSE9598 | GEO
Project description:Genetic variation is responsible for the generation of phenotypic diversity, including susceptibility to disease. Two major types of variation are known: single nucleotide polymorphisms (SNPs) and a more recently discovered structural variation, involving changes in copy number (CNVs) of kilobase- to megabase-sized chromosomal segments. Variation caused by CNVs has exceeded the amount of SNP-based differences expected to exist between two unrelated humans. Furthermore, many CNVs have been associated with disease predisposition. It is unknown whether CNVs arise in somatic cells, but it is, however, generally assumed that normal cells are genetically identical. Here we show that CNVs are frequent in healthy somatic cells of adult humans. We tested 34 tissue samples from three subjects and, having analyzed for each tissue <10-6 of all cells expected in an adult human, we observed at least six CNVs, affecting a single organ or one or more tissues of the same subject. The CNVs ranged from 82-176 kb, often encompassing known genes, potentially affecting gene function. Our results point to a paradigm shift in the genetics of somatic cells and indicate that humans are commonly affected by somatic mosaicism for stochastic CNVs, which occur in a substantial fraction of cells. A considerable number of phenotypes and diseases affecting humans are a consequence of a somatic process. Thus, our conclusions will be important for the delineation of genetic factors behind these phenotypes. Consequently, biobanks should consider sampling multiple tissues in order to better address mosaicism in the studies of somatic disorders. Furthermore, forensic medicine laboratories should be sensitized to the issue of underestimated frequency of somatic CNV mosaicism. Keywords: copy number variation (CNV), phenotype diversity, somatic cells 31 experiments; each experiment consists of two hybridizations, i.e. regular and dye-swap (62 hybridizations in total); cerebellum from corresponding subject was used as a reference; additionally 12 control self-self hybridizations are included (cerrebellum vs self)
2008-09-16 | E-GEOD-9598 | biostudies-arrayexpress
Project description:Somatic copy-number mosaicism in human skin revealed by induced pluripotent stem cells
| PRJNA177961 | ENA
Project description:This study examines genomic copy-number variation between two African cichlid species through array comparative genomic hybridization. Probe level hybridization ratios were compared to copy number variation identified in Illumina and Pacific Biosciences genome assemblies from both species. Array comparative genomic hybridization was performed with 3 samples (1 replicate array setup) of genomic DNA from Maylandia zebra vs. Orechromis niloticus XX clone genomic DNA from University of Stirling clonal lines.
2019-12-14 | GSE141976 | GEO
Project description:Somatic copy-number mosaicism in human skin revealed by induced pluripotent stem cells (sequencing)
| PRJNA178020 | ENA
Project description:Although it is known that cultured human cells acquire copy number variations over time, little is known about the mutation frequency in individual cells. Here we describe that human somatic and embryonic stem cell cultures show significant fractions of cells carrying unique chromosomal abnormalities, forming a non-clonal genetic mosaic. We studied 85 human single cells by array-based comparative genomic hybridisation and found that 14-31% of hESC and 8-26% of somatic cells are chromosomally abnormal. Remarkably, only 2 cells showed full-chromosome aneuploidy, while 93% of detected abnormalities were segmental, most of them telomere-spanning. Furthermore, fluorescent in situ hybridisation confirmed this finding and revealed an increased instability of the subtelomeric regions in hESC as compared to somatic cells.
2014-06-24 | GSE51126 | GEO
Project description:Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaic copy number gain of chromosome 1q is associated with cortical malformations, early-onset epilepsy, and developmental delay. Pathogenic brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in a neural progenitor cell during fetal development. However, in our cohort, in at least five of six patients with brain mosaic copy number gain of chromosome 1q, the alteration occurred pre-conception. We observed a third non-constitutive, but parentally-derived, haplotype for chromosome 1q in patient brain tissue, demonstrating that the copy number alteration occurred in a gamete pre-conception. The altered cells had no representation in parental buccal or proband blood or buccal samples, but were prominently observed in proband brain tissue, suggesting the copy number gain was lost in most cell lineages during embryonic development. Single-nuclei genotyping coupled with gene expression profiling revealed a strong enrichment of the chromosome 1q gain in astrocytes, which correlated with the unusual finding of hyaline astrocytic inclusions in all six cases.
2023-09-08 | GSE221849 | GEO
Project description:Clonal copy-number mosaicism in T-lymphocytes in NOD mice
| PRJNA472316 | ENA
Project description:Somatic mosaicism for DNA copy number alterations (SMC-CNA) is defined as gain or loss of chromosomal segments in mitotic cells within a single organism. As cells harboring SMC-CNA have the potential to undergo clonal expansion, SMC-CNA may be present in a substantial portion of cells in differentiated human tissues and may contribute to the predisposition of these cells to genetic disease including cancer. We characterized gross genomic alterations (>500 kbp) in uninvolved glandular tissue from 59 breast cancer patients and matched samples of primary tumors and lymph node metastases. Array based comparative genomic hybridization experiments showed 10% (6/59) of patients harbored 1 - 359 large SMC-CNA (mean: 1328 kbp; median: 961 kbp) in uninvolved glandular tissue. SMC-CNA were partially recurrent in tumors, albeit with considerable contribution of stochastic SMC-can, indicating genomic destabilization. Therefore, we hypothesized that the observed genomic destabilization is predetermined by mutations in genes related to maintenance of genomic integrity. Targeted resequencing of 301 known predisposition and somatic driver loci revealed mutations in the following genes: BRCA1 (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1 (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro) and TP53 (p.Arg306*). We demonstrated that gross SMC-CNA may be present in a substantial portion of glandular tissue cells, which are distant from that of the tumor cells, and may co-occur with point mutations in crucial cancer predisposing or somatic driver genes. Taken together, this highlights temporal and spatial neoplastic potential of uninvolved glandular tissue from breast cancer patients.
2015-07-31 | E-MTAB-3111 | biostudies-arrayexpress