Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA135363 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Copy number variants (CNVs) are a major source of genetic variation in human health and disease. Previous studies have suggested replication stress, such as that caused by the polymerase inhibitor aphidicolin, as a causative factor in CNV formation, but existing data are technically limited in the quality of the comparisons which can be made to experimentally induced variants. Here we used 1M feature single-nucleotide polymorphism (SNP) arrays and mate-pair sequencing as high resolution methods for characterizing CNVs in a common set of samples, to compare both the properties of constitutional and induced CNVs as well as the utility of the two methods in an experimental setting. Although the optimized methods provided complementary information, sequencing was more sensitive to small variants and provided superior structural descriptions that allowed some CNVs to be associated with inversions, ectopic duplications or LINE insertions. The majority of constitutional and all aphidicolin-induced CNVs appear to be formed via homology-independent mechanisms, while aphidicolin-induced CNVs were of a larger median size than constitutional events even when mate-pair data were considered. Aphidicolin thus appears to stimulate formation of CNVs that closely resemble human pathogenic CNVs and the subset of larger nonhomologous constitutional CNVs. One untreated and one aphidicolin-treated subclone of human fibroblast cell line HGMDFN090 were analyzed by Illumina HumanOmni1-Quad SNP array and low-density mate-pair sequencing.
2010-12-18 | E-GEOD-26121 | biostudies-arrayexpress
Project description:Copy number variants (CNVs) are a major source of genetic variation in human health and disease. Previous studies have suggested replication stress, such as that caused by the polymerase inhibitor aphidicolin, as a causative factor in CNV formation, but existing data are technically limited in the quality of the comparisons which can be made to experimentally induced variants. Here we used 1M feature single-nucleotide polymorphism (SNP) arrays and mate-pair sequencing as high resolution methods for characterizing CNVs in a common set of samples, to compare both the properties of constitutional and induced CNVs as well as the utility of the two methods in an experimental setting. Although the optimized methods provided complementary information, sequencing was more sensitive to small variants and provided superior structural descriptions that allowed some CNVs to be associated with inversions, ectopic duplications or LINE insertions. The majority of constitutional and all aphidicolin-induced CNVs appear to be formed via homology-independent mechanisms, while aphidicolin-induced CNVs were of a larger median size than constitutional events even when mate-pair data were considered. Aphidicolin thus appears to stimulate formation of CNVs that closely resemble human pathogenic CNVs and the subset of larger nonhomologous constitutional CNVs.
2010-12-18 | GSE26121 | GEO
Project description:Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that in many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis.
2011-10-12 | GSE32711 | GEO
Project description:Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that in many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. We analyzed 16 tissue samples from four patients. For each patient we analyzed the DNA of a primary colon tumor sample, a normal colon tissue sample, a metastatic liver tumor sample and a normal liver tissue sample. The normal colon and normal liver samples serve as a control for the primary and metastatic tumor samples.
2011-10-11 | E-GEOD-32711 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Genomic prediction (GP) based on single nucleotide polymorphisms (SNP) has become a broadly used tool to increase the gain of selection in plant breeding. However, using predictors that are biologically closer to the phenotypes such as transcriptome and metabolome may increase the prediction ability in GP. The objectives of this study were to (i) assess the prediction ability for three phenotypic traits using different omic datasets including sequence variants (SV), deleterious SV (dSV), tolerant SV (tSV), expression presence/absence variation (ePAV), gene expression (GE), transcript expression (TE), and metabolites (M) as single predictors in comparison to those using a SNP array; (ii) investigate the improvement in prediction ability when combining multiple omic datasets information to predict phenotypic variation in barley breeding programs; (iii) explore the relationship between genes and metabolites to unravel the metabolic pathway of the three above mentioned phenotypic traits.</p><p><strong>RESULTS:</strong> The prediction ability from genomic best linear unbiased prediction (GBLUP) for the three traits using dSV information was higher than when using tSV, all SV information, or the SNP array. Any predictors from the transcriptome (GE, TE, as well as ePAV) and metabolome provided higher prediction abilities compared to the SNP array and SV on average across the three traits. In addition, some (di)-similarity existed between different omic datasets, and therefore provided complementary biological perspectives to phenotypic variation. Optimal combining the information of dSV, TE, ePAV, as well as metabolites into GP models could improve the prediction ability over that of the single predictors alone.</p><p><strong>CONCLUSIONS:</strong> The use of integrated omic datasets in GP model is highly recommended. Furthermore, we evaluated a cost-effective approach generating 3’end mRNA sequencing with transcriptome data extracted from seedling without losing prediction ability in comparison to the full-length mRNA sequencing, paving the path for the use of such prediction methods in commercial breeding programs.</p>
2022-03-18 | MTBLS1561 | MetaboLights
Project description:Affymetrix SNP array data for paediatric ependymoma and constitutional DNA
| PRJNA147557 | ENA
Project description:We used a Drosophila melanogaster line (a "double balancer") carrying balancer chromosomes for both the second (CyO) and third (TM3) chromosomes. We crossed the double balancer to an isogenic wild-type "virginizer" line to obtain trans-heterozygous adults from the F1 generation. Whole-genome sequencing and mate pair sequencing were used to identify Single Nucleotide Variants (SNVs) and Structural Variants (SVs) on both chromosomes.
2019-05-02 | E-MTAB-7510 | biostudies-arrayexpress