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ENG prof: DNA forensics can spot guilty twin By Tim Stoddard
When Darrin Fernandez was charged this spring with raping a young woman in Dorchester in 2001, his lawyers argued that DNA evidence linking him to the crime wasn’t as damning as it seemed: Darrin’s twin brother, Damien, could be the rapist, they said, because identical twins have the same genetic profile. “But that’s just not true,” says Cassandra Smith, an ENG professor of biomedical engineering. “It’s simply incorrect to say that you cannot distinguish identical twins at the DNA level. It’s a common misconception, and it needs to be corrected.” Smith called the district attorney’s office this past May and offered to help. Research techniques she’s developed at BU, she said, could identify the subtle genetic differences between identical twins that crime labs cannot. A week before the case went to trial in June, she testified before a judge that she could determine whether it was Darrin’s or Damien’s DNA that was recovered from the victim. But because such tests could take between six months and two years to complete, and cost up to $100,000, the judge decided to forgo them and proceed with the trial. When the jury was unable to reach a verdict, the judge ordered a retrial for later this year. Meanwhile, Smith, who is also deputy director of the Center for Advanced Biotechnology and a professor at the School of Medicine, may soon be called in as an expert witness in a similar rape trial involving identical twins in Grand Rapids, Mich. As the district attorneys there consider whether to use Smith’s DNA tests, she is trying to design a faster and cheaper method. A closer look DNA fingerprinting was discovered 20 years ago this month, and while it has become widely accepted in the judicial system, Smith says that the standard tests used by the FBI and police are not detailed enough to distinguish between identical twins. In most crime labs, a technician extracts DNA from an evidentiary sample such as blood, semen, bone, or hair, and locates 13 different markers, or stretches of DNA, that vary in length from person to person. Each marker in the sample is measured and compared with the complementary marker in a suspect’s DNA. The chances are extremely small that two people in a random population will match at all 13 sites. But among first-degree relatives such as fathers and sons, the chances of a match are much higher, and according to Smith, identical twins will almost certainly match at all 13 sites. The only way to distinguish identical twins at the DNA level is to look elsewhere in the genome, a person’s entire genetic blueprint. Monozygotic (identical) twins are the product of one sperm fertilizing one egg, which then splits into two identical embryos with the same genome. But soon after the split, each twin begins accruing unique changes in his or her DNA. “As we live and breathe, we accumulate mutations,” says Smith. “The trick is finding them.” Locating these mutations in the genome is daunting, because they could be within almost any of the 3.1 billion units in the genetic code. Smith and her colleagues have developed a two-step process to expedite the search. The first stage is mostly reconnaissance: a quick scan of both twins’ genome turns up hundreds of markers that may be unique to each. Then they take a closer look at those areas using conventional DNA sequencing techniques. Changes occur in many ways. Each time a cell divides, it makes a complete copy of its DNA, which is passed on to the daughter cell. The template DNA is often incorrectly copied, and small errors are passed on. Chemicals in the environment and ultraviolet radiation can also cause DNA to mutate. Other processes can effect changes in the DNA of certain cells. If one twin develops an infection, for example, his immune system will manufacture antibodies to neutralize the specific virus or bacterium. Antibodies are produced by a white blood cell, and to custom-fit each antibody to its target, certain genes in these cells rearrange slightly, producing a signature DNA sequence. Smith is also using this technique to study the genetic causes of schizophrenia. She’s identified sets of identical twins in which only one has developed the disease. Her goal is to determine the genetic changes that lead to the onset of schizophrenia, and perhaps some day develop preventive treatments. Smith may also use these techniques to launch a business for analyzing the DNA of cloned animals. Companies cloning animals and plants for research and agriculture currently do little genetic quality control, she says. A clone is supposed to be an exact replica of its parent, but researchers do not have the resources to test whether a clone’s DNA is a complete and accurate copy of its parent’s DNA. In many cases, an apparently healthy cloned fish or sheep may harbor unseen genetic defects. Smith’s company would be able to identify those problems early on, stemming potential financial and environmental calamities. In the coming months, Smith hopes to help solve the rape cases in Boston and in Grand Rapids. She would like to collaborate with researchers in Europe who may help her develop faster and cheaper tests. She is confident that her technique, or one very similar to it, will soon improve DNA forensics. “In my view, the testing will be done,” she says. “The only question is when.” |
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17
September 2004 |