Segmental chromosomal imbalances arise at high frequency in human fibroblasts
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PROVIDER: PRJNA302485 | ENA |
REPOSITORIES: ENA
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Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75089 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75098 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75093 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75088 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75068 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75065 | GEO
Project description:Preservation of a balanced chromosomal content is regarded to be a key point for the success of multicellular organisms. Chromosomal segregation takes place under the strict control of well-orchestrated cell-cycle checkpoints, consequently leading to accurate transmission of intact chromosomes. Estimates of the whole chromosomal error rates per cell division based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. Recent sporadic studies of single cell genome wide CNV analysis suggested that the error rate might be higher than currently estimated. To obtain accurate measures of chromosomal error rates, we plated single fibroblast and analyzed the two daughter sister cells following a single cell division. In total 14 single fibroblasts derived from 7 mitoses carried segmental aneuploidies in a total of 178 cells from 5 different cell lines that were analyzed after a single cell division, indicating a mean frequency of 7.9% in vitro. In conclusion, the chromosomal stability is hundreds times lower than the current dogma, showing that chromosomal instability is a common place and putting the efficacy of the DNA-repair mechanisms and control checkpoints in question.
2016-05-01 | GSE75069 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-05-01 | GSE75116 | GEO
Project description:Segmental chromosomal imbalances arise at high frequency in human fibroblasts (S2)
| PRJNA302480 | ENA
Project description:Segmental chromosomal imbalances arise at high frequency in human fibroblasts (S1)
| PRJNA302477 | ENA