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April 8, 2013

Twin DNA Differences

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Geneticists are discovering that identical twins don't have identical DNA. As this ScienCentral News video explains, this surprising research could help scientists better understand genetic diseases in the rest of us.


Interviewees: Julia & Claire Calzonetti, Identical twin; Jan Dumanski, University of Alabama at Birmingham
Length: 1 min 26 sec
Produced by Joyce Gramza & Jessica Tanenbaum
Edited by Jessica Tanenbaum/Chris Bergendorff
Copyright © ScienCentral, Inc.

One Zygote, Two Genomes

For identical twins, the equation always has been simple: same egg + same sperm = same DNA. But new research from the American Journal of Human Genetics says this formula is not quite right. According to geneticist Jan Dumanski and his colleagues, identical twins don't have matching DNA.

"In medical textbooks or in popular science books, it's very often written that identical twins are identical also in the DNA," says Dumanski. "And that's not true. We are challenging this dogma by finding these small subtle but clearly detectable differences in the DNA of identical twins."

Although researchers previously have documented a few, rare genetic differences between identical twins, Dumanski says such cases were considered exceptions. "It was, in the field, considered rather as a curiosity that they really differ. What we show is that these differences are actually very, very frequent," he explains. "We basically see those differences in every twin pair we looked at so far."

For their study, Dumanski and colleagues compared the genomes of 19 twin pairs using DNA chip technology. For some of their volunteer pairs, one twin had Parkinson's disease while the other was healthy. Until now, scientists would attribute such a difference to environment rather than genetics. But Dumanski's research shows genetics might play a role.

He found that while twin pairs had identical gene sequences, they differed in how many copies they had of certain genes. Recent research has shown that differences in gene copy number can be important to how our bodies function in health and disease.

Dumanski says that because of his team's findings, the large existing body of twin studies might need some revision, and predicts their work will certainly influence future twin studies. Scientific studies of twins typically rely on the assumption that identical twins have identical DNA. Any characteristics the twins don't share are therefore attributed to subtle differences in environment or life experience. But if twin DNA doesn't match, then scientists will need to take that into account in assessing whether nature or nurture causes two twins to diverge.

"We definitely do not overturn the influence of the environment on the outside characteristics or traits of identical twins," explains Dumanski. "We are just saying that this picture has to be a little modified—that we do have on top of environmental influences also genetics, which is important, or possibly important for development of the differences between identical twins," he says.

Because identical twins do have identical gene sequences, Dumanski says they are still special. "Identical twins are very well aware that they are very special, that they are very interesting experiments that nature is doing for us," he says. "And they are also well aware that possible differences in their outside characteristics might lead scientists to discover about disease predispositions. So they are very cooperative…I certainly would like to encourage all identical twins to continue these type of tight collaborations with scientists like me, in genetic research of common disorders."

For example, if one twin has a version of the well-known BRCA1 gene that greatly increases the risk of breast cancer, the other twin has it too. While twins do have the same genes, the new study shows that twins don't always have the same number of copies of those genes. That is, twin A could have three BRCA1 genes, while twin B only has one.

Dumanski says geneticists don't yet have a good handle on the consequences of having different numbers of copies of certain genes because this area of research is so new. "We still don't know how much exactly of those changes we have, not only between two identical twins, but also between two unrelated individuals," he says.

For some genes, one copy is healthy, but too many copies cause disease. For other genes, people with very different copy numbers can all be healthy. Studying identical twins, Dumanski says, could help geneticists figure out which genes tend to duplicate and how these duplications arise. "These findings might be important for our future studies of disease predisposition" in twins and non-twins alike, he says.

Identical twins Julia and Claire Calzonetti can't always tell themselves apart in childhood photos.
image: Julia and Claire Calzonetti
Dumanski's news might be a surprise for geneticists, but identical twins Claire and Julia Calzonetti have already accepted the fact that they're not truly identical—Claire had her appendix removed, for one thing. But on the outside, the two women look pretty darn similar. They say people regularly mix them up, despite any genetic differences Claire and Julia may have.

Julia says, "People get really confused. They're like, 'What? What? I just said hi to you like five minutes ago and now she's ignoring me.' " And Claire says she gets hugs from strangers who think she's Julia. "You don't know who to say hi to, because they're like waiting for you to say hi, but you don't know them," says Claire.

If people could instantly scan Julia and Claire's DNA, maybe they wouldn't be so confused.

This research was published in the American Journal of Human Genetics on March 3, 2008 and was funded by the University of Alabama at Birmingham Medical School, the Swedish Cancer Society, the Swedish Children's Cancer Foundation, the U.S. Army, and the Netherlands Genomics Initiative.

       email to a friend by Jessica Tanenbaum

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