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Twin Study Suggests Some Epigenetic Marks Heritable
January 19, 2009
By Andrea Anderson
Type size: - + Email Print RSS Feed NEW YORK (GenomeWeb News) – Epigenetic differences are widespread across the genome, even in identical twins. But despite this variability, new research demonstrates that identical, or monozygotic, twins share more epigenetic marks than non-identical twins — suggesting epigenetic patterns are at least partly heritable.

An international team of researchers used a combination of microarrays and sodium bisulfite sequencing to assess genome-wide methylation differences within and between identical and non-identical twin sets. They found differences across the epigenomes of monozygotic twins, though such changes were less common in regulatory regions of the genome.

Overall, the researchers found that the epigenomes of monozygotic twins were more similar than those of non-identical, or dizygotic, twins, suggesting monozygotic twins inherit and maintain some of the same epigenetic signatures. The paper appeared online yesterday in the advanced online edition of Nature Genetics.

“Our findings represent a new way to look for the molecular cause of disease, and eventually may lead to improved diagnostics and treatment,” senior author Art Petronis, a researcher affiliated with the University of Toronto and Toronto’s Centre for Addiction and Mental Health, said in a statement.

Despite the emphasis put on genetics for understanding human traits, even monozygotic twins — who share the same genetic sequences — can have different phenotypes and disease risks, Petronis told GenomeWeb Daily News. Potential explanations for this so-called discordance or phenotypic dissimilarity may be found in epigenetics and environmental factors.

But environmental exposures are often difficult to characterize and don’t always explain phenotypic differences, Petronis said, explaining that despite the research done in this field very few good environmental risk candidates have been discovered. Instead, he and his colleagues speculated that stochastic epigenetic changes may be more common than previously believed.

For the latest paper, Petronis and his co-workers used 12K CpG island microarrays to look at the methylation patterns in white-blood cells and buccal epithelial cells, the cells lining the inside of the cheek, for dozens of pairs of monozygotic and dizygotic twins. They also compared the epigenetic profiles in cells from gut biopsies in 114 monozygotic twins.

This microarray analysis gave the researchers a look at large-scale methylation patterns in the twins’ genomes, Petronis said. They verified some of these loci using bisulfite sequencing. Using this approach, the researchers found differences across the epigenomes of identical twins. “Now we see that these epigenetic differences are very common,” Petronis said.

Despite the differences in the epigenetic patterns from one twin to the other, some regions of the epigenome remained fairly similar. In particular, promoter regions and CpG islands had a high degree of conservation, which Petronis said might reflect the functional importance of these regions.

While he said it’s possible that environmental differences account for the epigenetic differences between twins, Petronis and his colleagues believe many of the epigenetic patterns arise spontaneously. Whereas DNA replication is a high fidelity process with very few errors, Petronis explained, epigenetic signals are lower fidelity — and, consequently, more prone to errors and changes.

This stochastic epigenetic variation would be consistent with animal studies suggesting animals with the same genes, raised in the same environment, had fairly wide phenotypic variance, Petronis noted.

For the second part of the study, the researchers compared epigenetic patterns in identical and non-identical twins. Because monozygotic twins have the same epigenome before the embryo splits, the team reasoned, comparing the epigenetic differences in monozygotic and dizygotic twins provides a peek into epigenomic inheritance and maintenance.

In general, the researchers found that monozygotic twins had more similar epigenomes than dizygotic twins, suggesting at least a certain degree of epigenetic heritability.

While a multi-billion dollar enterprise is dedicated to unraveling the DNA sequence of human and other genomes, Petronis argued, these inherited epigenetic patterns probably explain at least some of the heritability missing from existing genome-wide association studies.

Calling his team’s research a “preliminary, pilot study,” Petronis said he believes more research into the epigenome will complement the existing “DNA-centric paradigm.” In order to gain more confidence in the results and to understand how epigenetic patterns vary and influence certain parts of the genome, though, Petronis said he’d like to see similar studies done looking at the entire epigenome of many more sets of monozygotic and dizygotic twins.