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Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements
Date
2017
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Article
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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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Citation
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. Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements. Am J Hum Genet. 2017 Oct 5;101(4):616-622.
Keywords
Genomic disorder, 22q11.2 deletion syndrome, 22q11.2DS,, VCFS, DiGeorge syndrome, Microdeletion, Inversion polymorphism, Ffiber-FISH, Low-copy repeats, Segmental duplications