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

Wolfram Demaerel; Matthew S. Hestand; Elfi Vergaelen; Ann Swillen; Marcos Lopez-Sanchez; Luis A. Perez-Jurado; Donna M. McDonald-McGinn; Elaine Zackai; Beverly S. Emanuel; Bernice E. Morrow; Jeroen Breckpot; Koenraad Devriendt; Int 22q11 2 Brain & Behav Consort; Thérèse van Amelsvoort; Joris R. Vermeesch

doi:10.1016/j.ajhg.2017.09.002

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

Wolfram Demaerel, Matthew S. Hestand, Elfi Vergaelen, Ann Swillen, Marcos Lopez-Sanchez, Luis A. Perez-Jurado, Donna M. McDonald-McGinn, Elaine Zackai, Beverly S. Emanuel, Bernice E. Morrow, Jeroen Breckpot, Koenraad Devriendt, Int 22q11 2 Brain & Behav Consort, Thérèse van Amelsvoort, Joris R. Vermeesch^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	616-622
Number of pages	7
Journal	American Journal of Human Genetics
Volume	101
Issue number	4
DOIs	https://doi.org/10.1016/j.ajhg.2017.09.002
Publication status	Published - 5 Oct 2017

Keywords

WILLIAMS-BEUREN-SYNDROME
CARDIO-FACIAL SYNDROME
LOW-COPY REPEATS
HUMAN-GENOME
DELETION SYNDROME
SEGMENTAL DUPLICATIONS
DIGEORGE/VELOCARDIOFACIAL SYNDROME
STRUCTURAL VARIATION
COMMON INVERSION
SUSCEPTIBILITY

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10.1016/j.ajhg.2017.09.002

Cite this

Demaerel, W., Hestand, M. S., Vergaelen, E., Swillen, A., Lopez-Sanchez, M., Perez-Jurado, L. A., McDonald-McGinn, D. M., Zackai, E., Emanuel, B. S., Morrow, B. E., Breckpot, J., Devriendt, K., Int 22q11 2 Brain & Behav Consort, van Amelsvoort, T., & Vermeesch, J. R. (2017). Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements. American Journal of Human Genetics, 101(4), 616-622. https://doi.org/10.1016/j.ajhg.2017.09.002

@article{dfe8aa05d3f244268000dc14d52e6846,

title = "Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements",

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.",

keywords = "WILLIAMS-BEUREN-SYNDROME, CARDIO-FACIAL SYNDROME, LOW-COPY REPEATS, HUMAN-GENOME, DELETION SYNDROME, SEGMENTAL DUPLICATIONS, DIGEORGE/VELOCARDIOFACIAL SYNDROME, STRUCTURAL VARIATION, COMMON INVERSION, SUSCEPTIBILITY",

author = "Wolfram Demaerel and Hestand, {Matthew S.} and Elfi Vergaelen and Ann Swillen and Marcos Lopez-Sanchez and Perez-Jurado, {Luis A.} and McDonald-McGinn, {Donna M.} and Elaine Zackai and Emanuel, {Beverly S.} and Morrow, {Bernice E.} and Jeroen Breckpot and Koenraad Devriendt and {Int 22q11 2 Brain & Behav Consort} and {van Amelsvoort}, Th{\'e}r{\`e}se and Vermeesch, {Joris R.}",

year = "2017",

month = oct,

day = "5",

doi = "10.1016/j.ajhg.2017.09.002",

language = "English",

volume = "101",

pages = "616--622",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

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Demaerel, W, Hestand, MS, Vergaelen, E, Swillen, A, Lopez-Sanchez, M, Perez-Jurado, LA, McDonald-McGinn, DM, Zackai, E, Emanuel, BS, Morrow, BE, Breckpot, J, Devriendt, K, Int 22q11 2 Brain & Behav Consort, van Amelsvoort, T & Vermeesch, JR 2017, 'Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements', American Journal of Human Genetics, vol. 101, no. 4, pp. 616-622. https://doi.org/10.1016/j.ajhg.2017.09.002

TY - JOUR

T1 - Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements

AU - Demaerel, Wolfram

AU - Hestand, Matthew S.

AU - Vergaelen, Elfi

AU - Swillen, Ann

AU - Lopez-Sanchez, Marcos

AU - Perez-Jurado, Luis A.

AU - McDonald-McGinn, Donna M.

AU - Zackai, Elaine

AU - Emanuel, Beverly S.

AU - Morrow, Bernice E.

AU - Breckpot, Jeroen

AU - Devriendt, Koenraad

AU - Int 22q11 2 Brain & Behav Consort

AU - van Amelsvoort, Thérèse

AU - Vermeesch, Joris R.

PY - 2017/10/5

Y1 - 2017/10/5

N2 - 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.

AB - 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.

KW - WILLIAMS-BEUREN-SYNDROME

KW - CARDIO-FACIAL SYNDROME

KW - LOW-COPY REPEATS

KW - HUMAN-GENOME

KW - DELETION SYNDROME

KW - SEGMENTAL DUPLICATIONS

KW - DIGEORGE/VELOCARDIOFACIAL SYNDROME

KW - STRUCTURAL VARIATION

KW - COMMON INVERSION

KW - SUSCEPTIBILITY

U2 - 10.1016/j.ajhg.2017.09.002

DO - 10.1016/j.ajhg.2017.09.002

M3 - Article

SN - 0002-9297

VL - 101

SP - 616

EP - 622

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 4

ER -