Small deletion variants have stable breakpoints commonly associated with Alu elements

de Smith, Adam J., Walters, Robin G., Coin, Lachlan J. M., Steinfeld, Israel, Yakhini, Zohar, Sladek, Rob, Froguel, Philippe and Blakemore, Alexandra I. F. (2008) Small deletion variants have stable breakpoints commonly associated with Alu elements. PLoS ONE, 3 8: e3104.1-e3104.11. doi:10.1371/journal.pone.0003104

Author de Smith, Adam J.
Walters, Robin G.
Coin, Lachlan J. M.
Steinfeld, Israel
Yakhini, Zohar
Sladek, Rob
Froguel, Philippe
Blakemore, Alexandra I. F.
Title Small deletion variants have stable breakpoints commonly associated with Alu elements
Formatted title
Small deletion variants have stable breakpoints commonly associated with Alu elements
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2008-08-01
Year available 2008
Sub-type Article (original research)
DOI 10.1371/journal.pone.0003104
Open Access Status DOI
Volume 3
Issue 8
Start page e3104.1
End page e3104.11
Total pages 11
Place of publication San Francisco, United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted abstract
Copy number variants (CNVs) contribute significantly to human genomic variation, with over 5000 loci reported, covering more than 18% of the euchromatic human genome. Little is known, however, about the origin and stability of variants of different size and complexity. We investigated the breakpoints of 20 small, common deletions, representing a subset of those originally identified by array CGH, using Agilent microarrays, in 50 healthy French Caucasian subjects. By sequencing PCR products amplified using primers designed to span the deleted regions, we determined the exact size and genomic position of the deletions in all affected samples. For each deletion studied, all individuals carrying the deletion share identical upstream and downstream breakpoints at the sequence level, suggesting that the deletion event occurred just once and later became common in the population. This is supported by linkage disequilibrium (LD) analysis, which has revealed that most of the deletions studied are in moderate to strong LD with surrounding SNPs, and have conserved long-range haplotypes. Analysis of the sequences flanking the deletion breakpoints revealed an enrichment of microhomology at the breakpoint junctions. More significantly, we found an enrichment of Alu repeat elements, the overwhelming majority of which intersected deletion breakpoints at their poly-A tails. We found no enrichment of LINE elements or segmental duplications, in contrast to other reports. Sequence analysis revealed enrichment of a conserved motif in the sequences surrounding the deletion breakpoints, although whether this motif has any mechanistic role in the formation of some deletions has yet to be determined. Considered together with existing information on more complex inherited variant regions, and reports of de novo variants associated with autism, these data support the presence of different subgroups of CNV in the genome which may have originated through different mechanisms.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
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