whole genome sequencing data for mice and cows Genome sequencing

Chromosomal abnormalities in mammalian preimplantation embryos are common but their molecular origin is not well understood. It was previously shown that segmental aneuploidy was linked to replication-dependent DNA damage in gene-poor regions of the genome. To better understand DNA replication patterns in preimplantation development, we performed analysis of DNA replication timing and correlated those with origin density, gene density, sites of G2 DNA synthesis, and with the location of both spontaneous and aphidicolin-induced chromosome breakage. We find that both bovine and mouse preimplantation embryos replicate gene poor regions late in the cell cycle relative to gene rich regions. Late replication timing and low gene density in the embryo correlates with a paucity of origins in mouse germ cells. Furthermore, low doses of aphidicolin treatment in mice, which slows replication below physiological speeds, is most limiting in late replicating regions with low origin density, and results in chromosome breakage in gene poor regions. Furthermore, sites of spontaneous chromosome breakage in bovine embryos are enriched in gene poor late replicating regions. Thus, low gene density, low origin density and late replication timing predispose specific regions to chromosome breakage during preimplantation development.