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The Genetic Journey: Following DNA from Cell to Society

The Genetic Journey: Following DNA from Cell to Society

The Genetic Journey: Following DNA from Cell to Society

DNA's tiny chemical bonds make us individuals and influence the health of populations. Follow the thread of life as we trace its complexity and explain how Johns Hopkins Bloomberg School of Public Health researchers are uncovering new insights into disease and life.

By Brian W. Simpson

SNPs: Cut to the Chase
Nearly 6 million American adults suffer from bipolar disorder, which can cause dramatic swings from manic to depressive episodes. Genetic epidemiologist Peter P. Zandi is part of a National Institute of Mental Health project that is hunting the genes that increase susceptibility to the disorder, which runs in families. Decades ago, scientists hoped they would find a single gene that was responsible and then come up with a drug treatment. Now they believe that multiple genes (perhaps more than a dozen) as well as other factors cause bipolar disorder. The NIMH project is enrolling 4,000 people with bipolar disorder and plans to examine 500,000 DNA markers called single nucleotide polymorphisms, or SNPs. "We use the SNPs as signposts to help locate genes that cause bipolar disorder," he says. "And by identifying the genes, we hope to develop more effective ways to prevent and treat the disorder."

And Now, the Epigenome
600 Icelanders may spark a revolution in the study of disease origins. It's long been known that chemical modifications to DNA (such as methylation) control gene expression. And, like genes themselves, these DNA modifications play a role in cancer and other diseases. What isn't known is how and why these modifications change over a lifetime. Do they act as slow-burn fuses that ignite genetic disorders later in life? "We think it may be one way to explain the age-dependent nature of some genetic problems," says genetic epidemiologist M. Daniele Fallin. She is studying the methylation changes in the DNA found in blood samples taken in the early 1990s compared to those taken recently from surviving participants of the Reykjavik Heart Study. In addition to shedding light on the best ways to measure methylation, the study may show that researching the epigenome is as important as studying the genome itself.

End of the Molecular Line
Look at your shoestrings. Each end has a tiny plastic cap, called an aglet, to keep them from fraying. Your chromosomes are similarly protected by a long repetition of DNA letters. As you age or are exposed to toxins, your chromosomal aglets (known as telomeres) are shortened. It's not a problem until the protective DNA letters are used up and vital DNA is damaged. When this happens, the cell usually knows not to replicate its DNA. If it does, genetic material may be damaged, which can sometimes lead to cancer. With Alan Meeker and Angelo De Marzo from Hopkins Medicine, cancer epidemiologist Elizabeth Platz focuses on telomeres and prostate cancer. They want to know if shorter telomeres can predict risk of prostate cancer, or its aggressiveness. They also are examining whether different telomere lengths explain why African Americans have a 60 percent higher risk of prostate cancer than whites.

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