title: One CNV Discordance in NRXN1 Observed Upon Genome-wide Screening in 38 Pairs of Adult Healthy Monozygotic Twins.
abstract: Monozygotic (MZ) twins stem from the same single fertilized egg and therefore share all their inherited genetic variation. This is one of the unequivocal facts on which genetic epidemiology and twin studies are based. To what extent this also implies that MZ twins share genotypes in adult tissues is not precisely established, but a common pragmatic assumption is that MZ twins are 100% genetically identical also in adult tissues. During the past decade, this view has been challenged by several reports, with observations of differences in post-zygotic copy number variations (CNVs) between members of the same MZ pair. In this study, we performed a systematic search for differences of CNVs within 38 adult MZ pairs who had been misclassified as dizygotic (DZ) twins by questionnaire-based assessment. Initial scoring by PennCNV suggested a total of 967 CNV discordances. The within-pair correlation in number of CNVs detected was strongly dependent on confidence score filtering and reached a plateau of r = 0.8 when restricting to CNVs detected with confidence score larger than 50. The top-ranked discordances were subsequently selected for validation by quantitative polymerase chain reaction (qPCR), from which one single ~120kb deletion in NRXN1 on chromosome 2 (bp 51017111-51136802) was validated. Despite involving an exon, no sign of cognitive/mental consequences was apparent in the affected twin pair, potentially reflecting limited or lack of expression of the transcripts containing this exon in nerve/brain.
authors.affiliation: Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Department of Statistics,Ewha Womans University,Seoul,South Korea.
authors.forename: Donghwan
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Genetics,University of North Carolina,Chapel Hill,NC,USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Szatkiewicz
authors.affiliation: Institute of Statistics,Jakarta,Indonesia.
authors.forename: Setia
authors.initials: S
authors.lastname: Pramana
authors.affiliation: Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
authors.forename: Shumei
authors.initials: S
authors.lastname: Teo
authors.affiliation: Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Department of Immunology,Genetics and Pathology,Rudbeck Laboratory and Science for Life Laboratory,Uppsala University,Uppsala,Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.affiliation: Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
mesh_terms: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D011795:Surveys and Questionnaires; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules
keywords: NRXN1; PennCNV; copy number variation; monozygotic twins; quantitative polymerase chain reaction