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 ß80%. 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.

Epigenetic discrimination of identical twins from blood under the forensic scenario

“…There is increasing evidence that MZ twins can demonstrate a very small degree of genetic differences, in terms of single nucleotide polymorphisms (SNPs) [2], copy number variations (CNVs) [3][4][5], Y-chromosome satellite DNA [6], and bone-marrow-derived memory B lymphocytes DNA sequences [7]. However, these sequence differences are extremely rare and difficult to locate.…”

Chromosomal scale length variation of germline DNA can predict individual cancer risk

“…Twin studies assume that monozygotic twins are genetically identical. This assumption, however, does not hold for copy number variation (27,28). Substantial difference in copy number variation occurs after conception.…”

Somatically acquired structural genetic differences: a longitudinal study of elderly Danish twins

“…6 So far, this strategy has been applied in a number of studies of phenotypically discordant as well as healthy or unselected MZ twins, and both mosaic and non-mosaic differences have been found. [6][7][8] In this study, we attempt to further explore the plasticity of the aging genome by searching for somatic structural variants acquired over a 10-year period in longitudinal samples from 86 elderly Danish MZ and dizygotic (DZ) twins. Furthermore, in a subset analysis, the genomes of the MZ twin pairs are compared to identify postzygotically acquired somatic structural variants.…”