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

International 22q11.2 Brain and Behavior Consortium

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)616-622
Number of pages7
JournalAmerican Journal of Human Genetics
Volume101
Issue number4
DOIs
StatePublished - Oct 5 2017

Keywords

  • 22q11.2 deletion syndrome
  • 22q11.2DS
  • DiGeorge syndrome
  • Genomic disorder
  • VCFS
  • fiber-FISH
  • inversion polymorphism
  • low-copy repeats
  • microdeletion
  • segmental duplications

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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