Article Text

U-type exchange is the most frequent mechanism for inverted duplication with terminal deletion rearrangements
  1. L R Rowe1,
  2. J-Y Lee2,
  3. L Rector1,
  4. E B Kaminsky2,
  5. A R Brothman1,3,4,
  6. C L Martin2,
  7. S T South1,3
  1. 1
    Institute for Clinical and Experimental Pathology, Associated Regional and University Pathologists (ARUP) Laboratories, Salt Lake City, Utah, USA
  2. 2
    Department of Human Genetics, Emory University, Atlanta, Georgia, USA
  3. 3
    Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA
  4. 4
    Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA
  1. Correspondence to Dr S T South, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA; sarah.south{at}


Background: Chromosomal rearrangements resulting in an interstitial inverted duplication with concomitant terminal deletion were first described for the short arm of chromosome 8 in 1976. Since then, this type of alteration has been identified and characterised for most chromosome arms. Three mechanisms are commonly proposed to explain the origin of this type of rearrangement. All three mechanisms involve formation of a dicentric chromosome that then breaks in a subsequent meiotic division to produce a monocentric duplicated and deleted chromosome. However, the events leading to the formation of the dicentric chromosome differ between the mechanisms. In one mechanism, either parent carries a paracentric inversion. This results in formation of a loop during meiotic pairing with a recombination event occurring in the loop. In the second mechanism, inverted low copy repeats in the same chromosome arm allow partial folding of one homologue onto itself with a recombination event between the inverted repeats. The third mechanism involves a pre-meiotic double-strand break with subsequent fusion, or U-type exchange, between the sister chromatids. The first two mechanisms require a single copy region to exist between the duplicated and deleted regions on the derivative chromosome, and therefore high resolution analysis of the rearrangement can be used to distinguish between these mechanisms.

Methods and results: Using G-banded chromosome analysis, fluorescence in situ hybridisation (FISH) and array comparative genomic hybridisation (CGH), we describe 17 new cases of inverted duplication with terminal deletion of 2q, 4p, 5p, 6q, 8p, 9p, 10q, 13q, 15q, 18p, 18q, and 22q.

Conclusions: These new cases, combined with previously described cases, demonstrate that U-type exchange is the most frequent mechanism for this rearrangement and can be observed on most, or perhaps all, chromosome arms.

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  • Funding This study was funded in part by the ARUP Institute for Clinical and Experimental Pathology and a grant from the Children’s Health Research Center at the University of Utah.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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