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      • One CNV Discordance in <i>NRXN1</i> Observed Upon Genome-wide Screening in 38 Pairs of Adult Healthy Monozygotic Twins

        Magnusson, Patrik K. E.,Lee, Donghwan,Chen, Xu,Szatkiewicz, Jin,Pramana, Setia,Teo, Shumei,Sullivan, Patrick F.,Feuk, Lars,Pawitan, Yudi Cambridge University Press 2016 TWIN RESEARCH AND HUMAN GENETICS - Vol.19 No.2

        <P>Monozygotic (MZ) twins stem from the same single fertilized egg and therefore share all their <I>inherited</I> 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 <I>r</I> = 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 <I>NRXN1</I> 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.</P>

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