%0 Journal Article
%T Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements
%A Ann Swillen
%A Bernice E. Morrow
%A Beverly S. Emanuel
%A Donna M. McDonald-McGinn
%A Elaine Zackai
%A Elfi Vergaelen
%A International 22q11.2 Brain and Behavior Consortium
%A Jeroen Breckpot
%A Koenraad Devriendt
%A Luis A. P谷rez-Jurado
%A Marcos L車pez-S芍nchez
%A Matthew S. Hestand
%A Wolfram Demaerel
%J Archive of "American Journal of Human Genetics".
%D 2017
%R 10.1016/j.ajhg.2017.09.002
%X 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每D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A每B 22q11.2 deletion carry inversions of LCR22B每D or LCR22C每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
%K Genomic disorder
%K 22q11.2 deletion syndrome
%K 22q11.2DS
%K VCFS
%K DiGeorge syndrome
%K microdeletion
%K inversion polymorphism
%K fiber-FISH
%K low-copy repeats
%K segmental duplications
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630191/