TY - JOUR
T1 - Phenotypically Concordant and Discordant Monozygotic Twins Display Different DNA Copy-Number-Variation Profiles
AU - Bruder, Carl E.G.
AU - Piotrowski, Arkadiusz
AU - Gijsbers, Antoinet A.C.J.
AU - Andersson, Robin
AU - Erickson, Stephen
AU - Diaz de Ståhl, Teresita
AU - Menzel, Uwe
AU - Sandgren, Johanna
AU - von Tell, Desiree
AU - Poplawski, Andrzej
AU - Crowley, Michael
AU - Crasto, Chiquito
AU - Partridge, E. Christopher
AU - Tiwari, Hemant
AU - Allison, David B.
AU - Komorowski, Jan
AU - van Ommen, Gert Jan B.
AU - Boomsma, Dorret I.
AU - Pedersen, Nancy L.
AU - den Dunnen, Johan T.
AU - Wirdefeldt, Karin
AU - Dumanski, Jan P.
N1 - Funding Information:
This study was supported by funds from the Health Services Foundation and the General Endowment Fund (HSF, GEF) from the University of Alabama at Birmingham Medical School, the Swedish Cancer Society, the Swedish Children's Cancer Foundation, and the U.S. Army Medical Research and Materiel Command (award no. W81XWH-04-1-0269 to J.P.D), as well as by Netherlands Genomics Initiative funds to the Center for Medical Systems Biology supporting A.A.C.H.G., J.T.d.D., D.I.B., and G.J.B.v.O. The twin specimens and phenotypic data were collected with the support of National Institutes of Health (NIH) grant ES10758 to N.L.P. S.E. acknowledges the support of NIH grant 5T32HL072757-04, and D.B.A. acknowledges the support of NIH grants 3P30DK056336-05S2 and 5R01ES009912-08.We thank Drs. Eline Slagboom and Claudia Ruivenkamp for sample contribution, guidance, and discussions, as well as Drs. Bruce A. Korf, Lisa Guay-Woodford, Jay McDonald, and Marco Marra for critical comments on the manuscript. We also thank Dr. Doug Horsman for valuable advice about the genetics of CLL.
PY - 2008/3/3
Y1 - 2008/3/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=40849109768&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2007.12.011
DO - 10.1016/j.ajhg.2007.12.011
M3 - Article
C2 - 18304490
AN - SCOPUS:40849109768
VL - 82
SP - 763
EP - 771
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -