Unique epigenetic profile found in identical twins

Identical twins carry a unique epigenetic signature on their DNA, providing potential clues as to how and why identical twinning occurs.

Identical or 'monozygotic' twins occur when a single embryo splits in two soon after fertilisation, leading to the development of two embryos with the same DNA. They occur at a rate of three to four per 1000 births, and it has been thought that splitting is a random event. Researchers in the Netherlands studying the DNA of thousands of identical twins have now found that they all share a clear 'signature' on their DNA.

'This is the first time that we have found a biological marker of this phenomenon in humans. The explanation appears not to lie in the genome, but in its epigenome,' said Professor Dorret Boomsma from the Vrije Universiteit Amsterdam (VU), lead author on the study, published in Nature Communications.

The epigenome is a term used to describe the pattern of chemical markers and modifications on the DNA, across the whole genome of an individual. These modifications act as regulators, controlling gene activation. This ensures that the right genes are switched on in the right tissues at the right time in development, or in response to specific environmental triggers.

Researchers examined the epigenomes from more than 3000 people who were monozygotic twins, and a similar number from people who were fraternal twins (non-identical twins that result from two different embryos). They found that identical twins uniquely shared a specific pattern of chemical modifications – known as DNA methylation – at 834 locations across their genomes.

Around 12 percent of pregnancies start out with multiple embryos, although only around two percent lead to multiple births – this is known as vanishing twin syndrome. The identified epigenetic signature can correctly determine whether someone is a monozygotic twin in around 80 percent of cases, even if they had lost a twin in the womb or been separated at birth. The researchers were not able to determine if someone was or had been a fraternal twin.

It is unknown whether these marks are a cause, a consequence, or a by-product, of the original embryo splitting. They seem to be located close to genes involved in embryo growth and development, including at genes that regulate cell-cell adhesion. The authors suggest that this may provide a possible explanation as to why these embryos are more prone to splitting. They hope that their research may help to shed light on why identical twins are predisposed to certain birth defects, such as spina bifida.

'These locations in the DNA are involved in functions in early embryonic development. In addition to insights into the fabrics of monozygotic twins, our results may lead to a better understanding of congenital abnormalities that occur more often in monozygotic twins in the future,' said co-author Dr Jenny van Dongen, also from VU.