Journal
GENES & DEVELOPMENT
Volume 29, Issue 9, Pages 898-903Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.261743.115
Keywords
aneuploidy; dosage-sensitive genes; Down syndrome; proliferation
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Funding
- National Institutes of Health [GM056800]
- Grants-in-Aid for Scientific Research [26290069, 25640115, 25108717] Funding Source: KAKEN
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Aneuploidy-the gain or loss of one or more whole chromosome-typically has an adverse impact on organismal fitness, manifest in conditions such as Down syndrome. A central question is whether aneuploid phenotypes are the consequence of copy number changes of a few especially harmful genes that may be present on the extra chromosome or are caused by copy number alterations of many genes that confer no observable phenotype when varied individually. We used the proliferation defect exhibited by budding yeast strains carrying single additional chromosomes (disomes) to distinguish between the few critical genes hypothesis and the mass action of genes hypothesis. Our results indicate that subtle changes in gene dosage across a chromosome can have significant phenotypic consequences. We conclude that phenotypic thresholds can be crossed by mass action of copy number changes that, on their own, are benign.
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