CNV Concordance in 1,097 MZ Twin Pairs

Area of Science:

• Genetics
• Developmental Biology
• Twin Studies

Background:

• Monozygotic (MZ) twins offer a unique model for studying somatic mutations due to their identical genetic makeup at conception.
• Copy number variants (CNVs) are a significant source of genetic variation with high mutation rates, potentially influencing phenotypic differences.
• Understanding de novo CNVs in MZ twins is crucial for dissecting genetic and environmental contributions to variation.

Purpose of the Study:

• To conduct a genome-wide survey for post-twinning de novo CNVs in a large cohort of MZ twin pairs.
• To compare CNV concordance rates between different DNA sources (blood and buccal epithelium).
• To explore potential associations between concordant CNVs and neurodevelopmental traits like thought problems (TP) and attention problems (AP).

Main Methods:

• Genome-wide analysis of 1,097 MZ twin pairs using Affymetrix 6.0 microarrays to detect CNVs.
• Utilized two CNV calling algorithms and performed quantitative PCR (qPCR) for validation of selected de novo CNVs.
• Compared CNV concordance rates across DNA sources and conducted gene-enrichment analyses for TP and AP.

Main Results:

• Identified 153 putative post-twinning de novo CNVs greater than 100 kb, with a majority located in the 15q11.2 region.
• Validated two de novo CNVs in one MZ twin pair via qPCR; 17 of 18 remaining putative CNVs were concordant deletions/duplications.
• Observed approximately 80% CNV concordance for calls not equal to two copies; buccal DNA showed slightly higher concordance, while blood DNA yielded more concordant CNVs per pair.

Conclusions:

• Post-twinning de novo CNVs are rare in MZ twins, with most identified variants being concordant deletions or duplications.
• DNA source impacts CNV detection and concordance rates, with buccal and blood DNA exhibiting distinct characteristics.
• No significant associations were found between concordant CNVs and thought or attention problems, suggesting other factors may be more influential for these traits.