학술논문
Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements
Document Type
Academic Journal
Author
Demaerel, Wolfram; Hestand, Matthew S.; Vergaelen, Elfi; Swillen, Ann; Lopez-Sanchez, Marcos; Perez-Jurado, Luis A.; McDonald-McGinn, Donna M.; Zackai, Elaine; Emanuel, Beverly S.; Morrow, Bernice E.; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R.; Antshel, Kevin; Arango, Celso; Armando, Marco; Bassett, Anne; Bearden, Carrie; Boot, Erik; Bravo-Sanchez, Marta; Breetvelt, Elemi; Busa, Tiffany; Butcher, Nancy; Campbell, Linda; Carmel, Miri; Chow, Eva; Crowley, T. Blaine; Cubells, Joseph; Cutler, David; Digilio, Maria Cristina; Duijff, Sasja; Eliez, Stephan; Emanuel, Beverly; Epstein, Michael; Evers, Rens; Fernandez Garcia-Moya, Luis; Fiksinski, Ania; Fraguas, David; Fremont, Wanda; Fritsch, Rosemarie; Garcia-Minaur, Sixto; Golden, Aaron; Gothelf, Doron; Guo, Tingwei; Gur, Ruben; Gur, Raquel; Heine-Suner, Damian; Hestand, Matthew; Hooper, Stephen; Kates, Wendy; Kushan, Leila; Laorden-Nieto, Alejandra; Maeder, Johanna; Marino, Bruno; Marshall, Christian; McCabe, Kathryn; McDonald-McGinn, Donna; Michaelovosky, Elena; Morrow, Bernice; Moss, Edward; Mulle, Jennifer; Murphy, Declan; Murphy, Kieran; Murphy, Clodagh; Niarchou, Maria; Ornstein, Claudia; Owen, Michael; Philip, Nicole; Repetto, Gabriela; Schneider, Maude; Shashi, Vandana; Simon, Tony; Tassone, Flora; Unolt, Marta; van Amelsvoort, Therese; van den Bree, Marianne; Van Duin, Esther; Vermeesch, Joris; Vicari, Stefano; Vingerhoets, Claudia; Vorstman, Jacob; Warren, Steve; Weinberger, Ronnie; Weisman, Omri; Weizman, Abraham; Zhang, Zhengdong; Zwick, Michael
Source
American Journal of Human Genetics. Oct 5, 2017, Vol. 101 Issue 4, 616
Subject
Language
English
ISSN
0002-9297
Abstract
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.ajhg.2017.09.002 Byline: Wolfram Demaerel (1), Matthew S. Hestand (1), Elfi Vergaelen (1), Ann Swillen (1), Marcos Lopez-Sanchez (2,3,4), Luis A. Perez-Jurado (2,3,4), Donna M. McDonald-McGinn (5,6), Elaine Zackai (5,6), Beverly S. Emanuel (5,6), Bernice E. Morrow (7), Jeroen Breckpot (1), Koenraad Devriendt (1), Joris R. Vermeesch [joris.vermeesch@kuleuven.be] (1,*), Kevin Antshel, Celso Arango, Marco Armando, Anne Bassett, Carrie Bearden, Erik Boot, Marta Bravo-Sanchez, Elemi Breetvelt, Tiffany Busa, Nancy Butcher, Linda Campbell, Miri Carmel, Eva Chow, T. Blaine Crowley, Joseph Cubells, David Cutler, Wolfram Demaerel, Maria Cristina Digilio, Sasja Duijff, Stephan Eliez, Beverly Emanuel, Michael Epstein, Rens Evers, Luis Fernandez Garcia-Moya, Ania Fiksinski, David Fraguas, Wanda Fremont, Rosemarie Fritsch, Sixto Garcia-Minaur, Aaron Golden, Doron Gothelf, Tingwei Guo, Ruben Gur, Raquel Gur, Damian Heine-Suner, Matthew Hestand, Stephen Hooper, Wendy Kates, Leila Kushan, Alejandra Laorden-Nieto, Johanna Maeder, Bruno Marino, Christian Marshall, Kathryn McCabe, Donna McDonald-McGinn, Elena Michaelovosky, Bernice Morrow, Edward Moss, Jennifer Mulle, Declan Murphy, Kieran Murphy, Clodagh Murphy, Maria Niarchou, Claudia Ornstein, Michael Owen, Nicole Philip, Gabriela Repetto, Maude Schneider, Vandana Shashi, Tony Simon, Ann Swillen, Flora Tassone, Marta Unolt, Therese van Amelsvoort, Marianne van den Bree, Esther Van Duin, Elfi Vergaelen, Joris Vermeesch, Stefano Vicari, Claudia Vingerhoets, Jacob Vorstman, Steve Warren, Ronnie Weinberger, Omri Weisman, Abraham Weizman, Elaine Zackai, Zhengdong Zhang, Michael Zwick Keywords Genomic disorder; 22q11.2 deletion syndrome; 22q11.2DS; VCFS; DiGeorge syndrome; microdeletion; inversion polymorphism; fiber-FISH; low-copy repeats; segmental duplications 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. Author Affiliation: (1) Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium (2) Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain (3) Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain (4) Centro de Investigacion Biomedica en Red de Enfermedades Raras, Barcelona, Spain (5) Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA (6) Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA (7) Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA * Corresponding author Article History: Received 22 February 2017; Accepted 16 August 2017 (miscellaneous) Published: September 28, 2017