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I.R.F. / Aging news / Cloning / 09110901

Cloning Procedure and Sub-chromosomal Mutations
Posted on: November 9, 2009

The mechanisms that have evolved to maintain genome stability during cell cycle progression are challenged when a somatic cell nucleus is placed in a meiotic environment such as the ooplasm. Chromosomal spindle aberrations ensue in the majority of reconstructed oocytes within 2 hours of transplantation, but it is not known if they recover or persist with the onset of embryonic divisions.

Scientists analyzed the chromosomal spindles and the karyotype of cumulus cell-derived mouse clones through the initial and hence most critical mitoses. Cloned embryos start out with less aneuploidy than fertilized embryos but surpass them after ES cell derivation, as measured by frequencies of chromosome trisomies and structural rearrangements.

Despite the limited proportion of cloned mouse embryos that reach late gestation, a phenotypic mutation lacking a karyotypic mark was found in a newborn mouse cloned in 2002 and has been inherited since by its offspring. These data concur with a prevalent epigenetic, rather than genetic, basis for cloned embryo failure, but they also warn against the temptation to think that all conditions of clones are epigenetic and recover during gametogenesis.

The cloning procedure is defenseless towards pre-existing or induced sub-chromosomal mutations that are below the experimental detection limit of the cytogenetic assay.

Source: Balbach ST, Jauch A, Bohm-Steuer B, Cavaleri FM, Han YM, Boiani M.; Chromosome stability differs in cloned mouse embryos and derivative ES cells.; Dev Biol. 2007 Aug 15;308(2):309-21. Epub 2007 Jun 2.
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