Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 3, 763-771, 14 February 2008
doi:10.1016/j.ajhg.2007.12.011
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Phenotypically Concordant and Discordant Monozygotic Twins Display Different DNA Copy-Number-Variation Profiles
Carl E.G. Bruder1, 
, 
, Arkadiusz Piotrowski1, Antoinet A.C.J. Gijsbers2, 3, Robin Andersson4, Stephen Erickson5, Teresita Diaz de Ståhl6, Uwe Menzel6, Johanna Sandgren7, Desiree von Tell1, Andrzej Poplawski1, Michael Crowley1, Chiquito Crasto1, E. Christopher Partridge1, Hemant Tiwari5, David B. Allison1, 5, Jan Komorowski4, Gert-Jan B. van Ommen2, 3, Dorret I. Boomsma8, Nancy L. Pedersen9, Johan T. den Dunnen2, 3, Karin Wirdefeldt9 and Jan P. Dumanski1, 6
1 Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-0024, USA
2 Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands
3 Center for Medical Systems Biology, 2300 RA Leiden, The Netherlands
4 Linnaeus Centre for Bioinformatics, Uppsala University, SE-75124 Uppsala, Sweden
5 Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Ryals Public Health Building, Suite 327, Birmingham, Alabama 35294-0022, USA
6 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden
7 Department of Surgical Sciences, Uppsala Academic Hospital, Uppsala University, SE-751 85 Uppsala, Sweden
8 Department of Biological Psychology, VU University, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands
9 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden
Corresponding authorAbstract
The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.
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