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• W2096254048 abstract "The Intergenic Breakage Model, which is the current model of structural genome evolution, considers that evolutionary rearrangement breakages happen with a uniform propensity along the genome but are selected against in genes, their regulatory regions and in-between. However, a growing body of evidence shows that there exists regions along mammalian genomes that present a high susceptibility to breakage. We reconsidered this question taking advantage of a recently published methodology for the precise detection of rearrangement breakpoints based on pairwise genome comparisons.We applied this methodology between the genome of human and those of five sequenced eutherian mammals which allowed us to delineate evolutionary breakpoint regions along the human genome with a finer resolution (median size 26.6 kb) than obtained before. We investigated the distribution of these breakpoints with respect to genome organisation into domains of different activity. In agreement with the Intergenic Breakage Model, we observed that breakpoints are under-represented in genes. Surprisingly however, the density of breakpoints in small intergenes (1 per Mb) appears significantly higher than in gene deserts (0.1 per Mb).More generally, we found a heterogeneous distribution of breakpoints that follows the organisation of the genome into isochores (breakpoints are more frequent in GC-rich regions). We then discuss the hypothesis that regions with an enhanced susceptibility to breakage correspond to regions of high transcriptional activity and replication initiation.We propose a model to describe the heterogeneous distribution of evolutionary breakpoints along human chromosomes that combines natural selection and a mutational bias linked to local open chromatin state." @default.
• W2096254048 created "2016-06-24" @default.
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• W2096254048 date "2009-07-24" @default.
• W2096254048 modified "2023-10-10" @default.
• W2096254048 title "Analysis of fine-scale mammalian evolutionary breakpoints provides new insight into their relation to genome organisation" @default.
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• W2096254048 doi "https://doi.org/10.1186/1471-2164-10-335" @default.
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