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

International 22q11.2 Brain and Behavior Consortium

Research output: Contribution to journalArticlepeer-review

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

Bibliographical note

Funding Information:
W.D. is a fellow at KU Leuven and is supported by IWT (131625). This work was made possible by grants from the KUL PFV/10/016 SymBioSys to J.R.V. and GOA/12/015 to J.R.V. and K.D, the FWO to J.V. (G.0E1117N), the National Institute of Mental Health (5U01MH101723-02), and the Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) program through the project IAP P7/43-BeMGI. L.A.P.J.?s lab was funded by the Marat? de TV3 (20153230), the Spanish Ministry of Economy and Competitiveness (Pi1302481), and the Catalan Department of Economy and Knowledge (2014SGR1468 and the ICREA Acad?mia award). J.V.R. was funded by the Jerome Lejeune Foundation (project #1665). The molar cell lines CHM1 and CHM13 were kindly provided by E. Eichler. D.M.M.-M has given lectures for Natera on 22q11.2 deletion syndrome. L.A.P.J. is a scientific advisor of qGenomics Laboratory, S.L..

Funding Information:
W.D. is a fellow at KU Leuven and is supported by IWT ( 131625 ). This work was made possible by grants from the KUL PFV/10/016 SymBioSys to J.R.V. and GOA/12/015 to J.R.V. and K.D, the FWO to J.V. ( G.0E1117N ), the National Institute of Mental Health ( 5U01MH101723-02 ), and the Belgian Science Policy Office Interuniversity Attraction Poles ( BELSPO-IAP ) program through the project IAP P7/43-BeMGI. L.A.P.J.’s lab was funded by the Marató de TV3 ( 20153230 ), the Spanish Ministry of Economy and Competitiveness ( Pi1302481 ), and the Catalan Department of Economy and Knowledge ( 2014SGR1468 and the ICREA Acadèmia award). J.V.R. was funded by the Jerome Lejeune Foundation (project # 1665 ). The molar cell lines CHM1 and CHM13 were kindly provided by E. Eichler. D.M.M.-M has given lectures for Natera on 22q11.2 deletion syndrome. L.A.P.J. is a scientific advisor of qGenomics Laboratory, S.L..

Publisher Copyright:
© 2017

Keywords

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

Fingerprint

Dive into the research topics of 'Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements'. Together they form a unique fingerprint.

Cite this