%0 Journal Article
%T Dosage compensation and the global re-balancing of aneuploid genomes
%A Matthias Prestel
%A Christian Feller
%A Peter B Becker
%J Genome Biology
%D 2010
%I BioMed Central
%R 10.1186/gb-2010-11-8-216
%X Complex genomes are more than just the sum of their genes, but are rather complex regulatory systems in which the expression of each individual gene is a function of the activity of many other genes, so that the levels of their protein products are maintained within a narrow range. Such homeostasis favors the maintenance of the appropriate stoichiometry of subunits in multiprotein complexes or of components in signal transduction pathways, and defines the 'ground state' of a cell [1]. In diploid genomes, both alleles of a gene are usually active and this 'double dose' of each gene is figured into the equation. Thus, deviations from diploidy, such as the deletion or duplication of genes or of larger chromosomal fragments (aneuploidy), unbalance the finely tuned expression of the genome. Segmental aneuploidies of this kind can arise from failed or faulty repair of chromosomal damage due to irradiation, chemical insult or perturbation of replication, or from illegitimate recombination during meiosis. Loss or duplication of entire chromosomes (monosomy or trisomy, respectively) can arise from non-disjunction during cell division. Depending on the extent of the aneuploidy and on the genes affected, the fine balance of trans-acting factors and their chromosomal binding sites that define the gene-expression system is disturbed, and the fitness of the cell or organism challenged.Often, aneuploidies have been associated with a variety of developmental defects and malignant aberrations, such as Down syndrome or certain breast cancers (reviewed in [2,3]). The phenotypes associated with changes in gene copy number can not only be the result of the deregulation of the affected gene(s), but may also reflect trans-acting effects on other chromosomal loci or even more global alterations of the entire regulatory system. This is particularly true if genes coding for regulatory factors, such as transcription factors, are affected (reviewed in [4,5]).Genome-wide studies in different or
%U http://genomebiology.com/2010/11/8/216