The same in (almost) every way: Study shows identical twins are not genetically identical

While identical twins are the same in many ways, a new study shows that their genes are a surprising exception to the rule. Using the gene chips, Dr. Richard O’Reilly, psychiatrist at Lawson Health Research Institute, and Dr. Shiva Singh, molecular geneticist at The University of Western Ontario, have found that identical twins are not necessarily genetically identical.

During normal reproductive development, a single cell forms by combining an egg, genetic material from the mother, and sperm, genetic material from the father. Once the cell has formed, it multiplies, dividing and differentiating into different organs to gradually form a fetus. In the case of identical twins, however, the egg first divides into two genetically identical halves. The result: monozygotic twins.

Since the cells form based on genetically identical copies, the assumption has been that identical twins have genetically identical development. Any differences between identical twins were attributed exclusively to environment, such as a difference in upbringing or exposure to chemicals. Indeed, this has been the standard approach to disentangling genetic versus environmental causation of somatic and behavioural traits. Recent findings indicate, however, that environment may not be the only factor causing differences in identical twins.

According to Dr. O’Reilly, the human genome is not static. “In the last five or six years we’ve discovered a very interesting type of genetic change called copy number variation,” he explains. “This is where people have different numbers of genes in their genome.” Once cells begin to divide and differentiate, they can lose or acquire additional stretches of DNA resulting in profound changes to development. “If you’ve got extra genes, they will produce extra gene product – protein – which can actually affect the human phenotype, including disease potential, abilities, and behavior,” Dr. O’Reilly says, and twins are no exception.

In the past, the assumption has been that if monozygotic twins are genetically identical, they should be equally susceptibility to genetic diseases. Dr. O’Reilly and his team study schizophrenia. If genes cause the illness then, if one member of the identical twins has schizophrenia, the risk for the other twin should be 100 per cent. However, studies have shown that the risk of the disease in both twins is only 50 per cent. Based on these inconsistent expressions, Dr. O’Reilly had the ideal opportunity to investigate and compare the potential source of difference.

“Our strategy was to use identical twins that are discordant – one has schizophrenia and the other one doesn’t – and identify all the genetic differences,” Dr. O’Reilly says. “When we looked across many pairs of these identical twins, we can see that there are common genes and genetic pathways that are changed in the individuals who go on to develop the illness. “ In total, Dr. O’Reilly and his team examined about a million markers. The results indicated that a whopping 12 per cent of DNA can vary between identical twins, a milestone discovery that will shift the thought surrounding human variation and genetic research.

“The discovery of copy number variation, and the ability now to actually look right through a person’s genes by total genome sequencing, is a remarkable advance over where we were even ten years ago,” Dr. O’Reilly says. “The next step is to look at the function of the affected genes and gene pathway. This will lead the way to more focused treatment interventions. In addition, if we had a genetic test for schizophrenia, it could be applied early in the disease when it’s hard to make that diagnosis.”

Dr. O’Reilly’s research was funded through the Canadian Institutes of Health Research, the Ontario Mental Health Foundation, and the Schizophrenia Society of Ontario. The study is published in the April edition of PLoS ONE.