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

Wolfram Demaerel, Matthew S. Hestand, Elfi Vergaelen, Ann Swillen, Marcos López-Sánchez, Luis A. Pérez-Jurado, Donna M. McDonald-McGinn, Elaine Zackai, Beverly S. Emanuel, Bernice E. Morrow, Jeroen Breckpot, Koenraad Devriendt, Zhengdong Zhang

Research output: Contribution to journalArticle

4 Citations (Scopus)

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)
JournalAmerican Journal of Human Genetics
DOIs
StateAccepted/In press - 2017

Fingerprint

Homologous Recombination
Chromosomes
Genomic Segmental Duplications
DiGeorge Syndrome

Keywords

  • 22q11.2 deletion syndrome
  • 22q11.2DS
  • DiGeorge syndrome
  • Fiber-FISH
  • Genomic disorder
  • Inversion polymorphism
  • Low-copy repeats
  • Microdeletion
  • Segmental duplications
  • VCFS

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Demaerel, W., Hestand, M. S., Vergaelen, E., Swillen, A., López-Sánchez, M., Pérez-Jurado, L. A., ... Zhang, Z. (Accepted/In press). Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements. American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2017.09.002

Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements. / Demaerel, Wolfram; Hestand, Matthew S.; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A.; McDonald-McGinn, Donna M.; Zackai, Elaine; Emanuel, Beverly S.; Morrow, Bernice E.; Breckpot, Jeroen; Devriendt, Koenraad; Zhang, Zhengdong.

In: American Journal of Human Genetics, 2017.

Research output: Contribution to journalArticle

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 & Zhang, Z 2017, 'Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements', American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2017.09.002
Demaerel, Wolfram ; Hestand, Matthew S. ; Vergaelen, Elfi ; Swillen, Ann ; López-Sánchez, Marcos ; Pérez-Jurado, Luis A. ; McDonald-McGinn, Donna M. ; Zackai, Elaine ; Emanuel, Beverly S. ; Morrow, Bernice E. ; Breckpot, Jeroen ; Devriendt, Koenraad ; Zhang, Zhengdong. / Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements. In: American Journal of Human Genetics. 2017.
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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.",
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AU - López-Sánchez, Marcos

AU - Pérez-Jurado, Luis A.

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AU - Emanuel, Beverly S.

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AU - Breckpot, Jeroen

AU - Devriendt, Koenraad

AU - Zhang, Zhengdong

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