TY - JOUR
T1 - Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and digeorge syndromes
AU - Delio, Maria
AU - Guo, Tingwei
AU - McDonald-Mcginn, Donna M.
AU - Zackai, Elaine
AU - Herman, Sean
AU - Kaminetzky, Mark
AU - Higgins, Anne Marie
AU - Coleman, Karlene
AU - Chow, Carolyn
AU - Jarlbrzkowski, Maria
AU - Bearden, Carrie E.
AU - Bailey, Alice
AU - Vangkilde, Anders
AU - Olsen, Line
AU - Olesen, Charlotte
AU - Skovby, Flemming
AU - Werge, Thomas M.
AU - Templin, Ludivine
AU - Busa, Tiffany
AU - Philip, Nicole
AU - Swillen, Ann
AU - Vermeesch, Joris R.
AU - Devriendt, Koen
AU - Schneider, Maude
AU - Dahoun, Sophie
AU - Eliez, Stephan
AU - Schoch, Kelly
AU - Hooper, Stephen R.
AU - Shashi, Vandana
AU - Samanich, Joy
AU - Marion, Robert
AU - Van Amelsvoort, Therese
AU - Boot, Erik
AU - Klaassen, Petra
AU - Duijff, Sasja N.
AU - Vorstman, Jacob
AU - Yuen, Tracy
AU - Silversides, Candice
AU - Chow, Eva
AU - Bassett, Anne
AU - Frisch, Amos
AU - Weizman, Abraham
AU - Gothelf, Doron
AU - Niarchou, Maria
AU - Van Den Bree, Marianne
AU - Owen, Michael J.
AU - Suñer, Damian Heine
AU - Andreo, Jordi Rosell
AU - Armando, Marco
AU - Vicari, Stefano
AU - Digilio, Maria Cristina
AU - Auton, Adam
AU - Kates, Wendy R.
AU - Wang, Tao
AU - Shprintzen, Robert J.
AU - Emanuel, Beverly S.
AU - Morrow, Bernice E.
N1 - Funding Information:
We thank all the individuals and family members for participating in this study. We also thank the many clinical support staff for their significant effort in obtaining informed consent and blood or saliva specimens. We appreciate technical assistance by Jidong Shan and Ms. Debbie Lewis in the Molecular Cytogenetics Core at the Albert Einstein College of Medicine. We appreciate the technical support from our summer student, Levi Teitz. We acknowledge Sylvie Laglois (BC Children’s Hospital, Vancouver, BC, Candada), Sarah Dyack (IWK Health Centre, Halifax, NS, Canada), and Rosanna Weksberg (Hispital for Sick Children, Toronto, ON, Canada) for collaboration with Eva Chow. We also thank David Reynolds and Kevin Lau for performing Sequenom assays in the Genomics Core at the Albert Einstein College of Medicine. We acknowledge National Institutes of Health grants HL84410 and HD070454, which provided funds for this research.
PY - 2013/3/7
Y1 - 2013/3/7
N2 - Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.
AB - Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.
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U2 - 10.1016/j.ajhg.2013.01.018
DO - 10.1016/j.ajhg.2013.01.018
M3 - Article
C2 - 23453669
AN - SCOPUS:84876416890
SN - 0002-9297
VL - 92
SP - 439
EP - 447
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -