Oct 24, 2014

Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells

PLoS Genetics
Ruth B McColeC-Ting Wu

Abstract

Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell. Here we address the process by which CNVs become depleted of UCEs. We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established thro...Continue Reading

  • References124
  • Citations4

References

  • References124
  • Citations4

Citations

Mentioned in this Paper

Conserved Sequence
Tumor Suppressor Genes
Gene Dosage
UCE 1022
Pluripotent Stem Cells
DNA Copy Number Changes
Imbalance
Exons
Genome
Segmental Duplications, Genomic

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