Genomics

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Segmental chromosomal imbalances arise at high frequency in human fibroblasts (SB)


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75089 | GEO | 2016/05/01

SECONDARY ACCESSION(S): PRJNA302483

REPOSITORIES: GEO

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