Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

Journal Article (Journal Article)

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.

Full Text

Duke Authors

Cited Authors

  • Demaerel, W; Hestand, MS; Vergaelen, E; Swillen, A; López-Sánchez, M; Pérez-Jurado, LA; McDonald-McGinn, DM; Zackai, E; Emanuel, BS; Morrow, BE; Breckpot, J; Devriendt, K; Vermeesch, JR; International 22q11.2 Brain and Behavior Consortium,

Published Date

  • October 5, 2017

Published In

Volume / Issue

  • 101 / 4

Start / End Page

  • 616 - 622

PubMed ID

  • 28965848

Pubmed Central ID

  • PMC5630191

Electronic International Standard Serial Number (EISSN)

  • 1537-6605

Digital Object Identifier (DOI)

  • 10.1016/j.ajhg.2017.09.002


  • eng

Conference Location

  • United States