title: CNV Concordance in 1,097 MZ Twin Pairs.
abstract: Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Abdel
authors.initials: A
authors.lastname: Abdellaoui
authors.affiliation: Avera Institute for Human Genetics,Avera McKennan Hospital & University Health Center,Sioux Falls,South Dakota,USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ehli
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Avera Institute for Human Genetics,Avera McKennan Hospital & University Health Center,Sioux Falls,South Dakota,USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Weber
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Mbarek
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Toos
authors.initials: T
authors.lastname: van Beijsterveldt
authors.affiliation: Department of Genetics,Rutgers,The State University of New Jersey,Piscataway,New Jersey,USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brooks
authors.affiliation: College of Medicine,University of Vermont,Burlington,Vermont,USA.
authors.forename: Jim J
authors.initials: JJ
authors.lastname: Hudziak
authors.affiliation: Department of Genetics,University of North Carolina,Chapel Hill,North Carolina,USA.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Eco J
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: Avera Institute for Human Genetics,Avera McKennan Hospital & University Health Center,Sioux Falls,South Dakota,USA.
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Davies
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D017209:Apoptosis / Q000235:genetics; D001288:Attention; D001773:Blood Cells / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D056915:DNA Copy Number Variations; D004200:Diseases in Twins / Q000235:genetics; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry; D009426:Netherlands; D055495:Neurogenesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013850:Thinking; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult
chemical_list: D004247:DNA
keywords: attention problems