Comprehensive analysis of structural variants in breast cancer genomes using single molecule sequencing
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PROVIDER: PRJNA671422 | ENA |
REPOSITORIES: ENA
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Project description:Comprehensive analysis of structural variants in breast cancer genomes using single molecule sequencing
| PRJNA671422 | ENA
Project description:Pathogenic Structural Variants in Leukemia Genomes
| PRJEB50975 | ENA
Project description:Genetic variation amongst individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single-nucleotide changes. In this manuscript we explore variation on an intermediate scale-particularly insertions, deletions, and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number among individuals. Sequencing of a subset of structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence-map of human structural variation-an important standard for genotyping platforms and a prelude to future individual genome sequencing projects. Keywords: comparitive genomic hybridization, copy number variation, structural variation, fosmid end sequencing CGH analysis targeted against sites identified by fosmid end sequencing. 8 HapMap samples (sources of libraries ABC7-ABC14) are hybed against NA15510 (source of fosmid library G248).
2008-05-01 | E-GEOD-10037 | biostudies-arrayexpress
Project description:Genetic variation amongst individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single-nucleotide changes. In this manuscript we explore variation on an intermediate scale-particularly insertions, deletions, and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number among individuals. Sequencing of a subset of structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence-map of human structural variation-an important standard for genotyping platforms and a prelude to future individual genome sequencing projects. Keywords: comparitive genomic hybridization, copy number variation, structural variation, fosmid end sequencing
2008-05-01 | GSE10037 | GEO
Project description:Genetic variation amongst individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single-nucleotide changes. In this manuscript we explore variation on an intermediate scale-particularly insertions, deletions, and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number among individuals. Sequencing of a subset of structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence-map of human structural variation-an important standard for genotyping platforms and a prelude to future individual genome sequencing projects. Keywords: comparative genomic hybridization
2008-05-01 | GSE10008 | GEO
Project description:Structural characterization of ribosome variants
| PRJNA414663 | ENA
Project description:Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.
2022-10-04 | GSE147123 | GEO
Project description:Genetic variation amongst individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single-nucleotide changes. In this manuscript we explore variation on an intermediate scale-particularly insertions, deletions, and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number among individuals. Sequencing of a subset of structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence-map of human structural variation-an important standard for genotyping platforms and a prelude to future individual genome sequencing projects. Keywords: comparative genomic hybridization The DNA samples are a panel of 8 Hapmap samples, described by E. Eichler et al. (2007, Nature 447, 161-165). This set of 7 female, and one male samples are from from the Coriell Cell Repository, and is comprised of samples from four populations: four Yoruban, two CEPH, one Chinese, and one Japanese. The reference sample, NA15510, is female and also from the Corriel Cell Repository. This sample has been extensively characterized, (for example in Tuzan et al. 2005, Nature Genetics 10, p1038) and has been recommended for use in CNV detection programs to allow meaningful comparison of data between studies (discussed in Scherer, et al. 2007, Nature Genetics Supplement 39: S7-S15). Each of these samples was hybridized in pairs with the reversed labeling polarities. Additionally, 3 self-self control hybridizations were carried out for the reference sample, NA15510, one on each hybridization date.
2008-05-01 | E-GEOD-10008 | biostudies-arrayexpress
Project description:Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long span paired-end-tag (PET) sequencing approach using 10 Kb genomic DNA inserts to study human genome structural variations (SVs). The use of 10 Kb insert size allows the identification of breakpoints within repetitive or homology containing regions of a few Kb in size and results in a higher physical coverage compared to small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and 2 non-cancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germline SVs, whereas tandem duplications, unpaired inversions, inter-chromosomal translocations, and complex rearrangements are overrepresented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures which are compatible with breakage-fusion-bridge cycles, and discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers. Structural variations of 15 human cancer samples and 2 human normal samples were identified by long span paired-end sequencing
2011-04-06 | E-GEOD-26954 | biostudies-arrayexpress
Project description:Adaptive Structural Variants Contributing to Human Brain Development Revealed by 1,026 Rhesus Macaque Genomes
| PRJNA916866 | ENA