Contrary to our previous beliefs, identical twins are not genetically identical. This surprising finding may be of great significance for research on hereditary diseases and for the development of new diagnostic methods. How can it be that one identical twin might develop Parkinson's disease, for instance, but not the other? Until now, the reasons have been sought in environmental factors. The current study complicates the picture.

The researchers studied 19 pairs of monozygotic, or identical, twins and found differences in copy number variation in DNA. Copy number variation (CNV) occurs when a set of coding letters in DNA are missing, or when extra copies of segments of DNA are produced. Humans receive one chromosome from their mother and one from their father, providing for two copies of the genome. In some cases, bits of DNA are missing from a chromosome, leaving the offspring with just one copy of that bit of DNA. In other instances, mutations may produce three, four or more copies of a particular bit of DNA. In most cases, variation in the number of copies likely has no impact on health or development. But in others, it may be one factor in the likelihood of developing a disease. Researchers at UAB( University of Alabama), Leiden University Medical Center and VU University, The Netherlands; and Uppsala University and Karolinska Institutet, Sweden recently published their findings.* “The presumption has always been that identical twins are identical down to their DNA,” said Carl Bruder, Ph.D. and Jan Dumanski, Ph.D., of UAB’s Department of Genetics and the study’s lead authors. “That’s mostly true, but our findings suggest that there are small, subtle differences due to CNV. Those differences may point the way to better understanding of genetic diseases when we study so-called discordant monozygotic twins….a pair of twins where one twin has a disorder and the other does not.” Bruder points out that one twin might develop a particular disease…Parkinson’s, for example…while the other does not. Previously, it was thought that environmental factors were the likely culprits, not genetics. Bruder and Dumanski think their findings indicate that CNV may play a critical role and this can be efficiently studied in identical twins. “More importantly, changes in CNV may tell us if a missing gene, or multiple copies of a gene, are implicated in the onset of disease,” Bruder said. “If twin A develops Parkinson’s and twin B does not, the region of their genome where they show differences is a target for further investigation to discover the basic genetic underpinnings of the disease.” The UAB lab is one of the few worldwide that can make the full genome BAC (bacterial artificial chromosome) arrays that are used to find the changed DNA regions.

The findings were published Feb. 14 online in the American Journal of Human Genetics.http://eproofing.dartmouthjournals.com/pdfproofing/ajhg0069r.pdf

The research was funded by support from UAB, the Swedish Cancer Society, the Swedish Children’s Cancer Foundation, the U.S. Army Research and Material Command, National Institutes of Health, The Netherlands Genomics Initiative and the National Institutes of Health.