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

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 beg...

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Bibliographic Details
Published in:PLoS genetics 2014-10, Vol.10 (10), p.e1004646
Main Authors: McCole, Ruth B, Fonseka, Chamith Y, Koren, Amnon, Wu, C-Ting
Format: Article
Language:English
Subjects:
Animals
Binding sites
Biology and Life Sciences
Cancer
Cancer cells
Cell culture
Chromosome Walking
Chromosomes
Conserved Sequence - genetics
Copy number variations
Datasets
DNA Copy Number Variations - genetics
Evolution, Molecular
Gene Dosage
Genetic aspects
Genetic research
Genome, Human
Genomes
Genomics
Humans
Induced Pluripotent Stem Cells
Mammals
Neoplasms - genetics
Neoplasms - pathology
Pluripotent Stem Cells - cytology
Sequence Deletion
Transcription factors
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Summary: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 through selection against UCE-disrupting CNVs without the requirement for meiotic divisions.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1004646