Apr 1, 2005 12:00 PM

Drilling Down on DNA

The Human Genome Project was an international Apollo program for biology. It took thousands of scientists 13 years and billions of dollars to unravel the software of Homo sapiens. Now that we know the human genetic code has 3 billion "letters" and some 20,000 protein-coding genes, the real work can finally begin. Labs all over the world are picking up where the Genome Project left off, drilling down to learn how DNA, RNA, proteins, and various chemicals all collaborate to make a healthy person. Here are six of the most promising projects.

International HapMap Project Science: The human genome has 10 million places where one person's genes are likely to differ from another's by just one letter. These places are called single nucleotide polymorphisms, or SNPs (pronounced "snips"). Clusters of SNPs tend to be inherited together – what's known as a haplotype. Goal: Personalized preventive medicine. Haplotype maps will help predict what diseases a person is likely to face and which drugs might help. The International HapMap Project has sketched out the million or so most informative SNPs. A final map is due this year. Alternative Splicing Database Consortium Science: The RNA encoded by one gene can be rearranged or spliced to code for two or more proteins. That's how 20,000 genes can make 100,000 proteins. Goal: To track down the splicing errors that are likely culprits for Alzheimer's, cancer, and diabetes. Alternative splicing helps a cell adapt, and different cells can splice together different versions of the same protein. The consortium has made available computational tools and data from nine animal species; a DNA chip to study splice variants in cancer is expected in 2005. Protein Kinase Research Consortium Science: Proteins work in highly organized, intersecting pathways. Kinases are the master switches that turn these assembly lines on and off, controlling when cells divide, transmit signals, or die. Goal: New compounds to turn kinases on and off. Labs in 11 countries are funded through 2009, hoping to follow up on several new, better-targeted cancer drugs that go after kinases, which if left in the "on" position can allow uncontrolled cell growth. Human Epigenome Project Science: Added to DNA, a chemical tag called a methyl group tells the cell "ignore this gene"; changes in the environment – in the womb and throughout life – affect which genes get blanked. Goal: Treatment of obesity, some psychoses, and cancer might be linked to epigenetic errors. Researchers should be done poring over the epigenetics of 3,000 genes, about 15 percent of the total, by the end of the year. Human Proteome Organisation Science: If genes are software, then proteins are hardware – the meat in the machine. The proteome includes every protein the human body makes, plus metadata (the where, when, and how much of each). For instance, enzymes, insulin, and hemoglobin are all proteins. Goal: To compile baseline inventories of proteins in blood, brain, and liver. Dozens of labs worldwide hope to use this data to figure out who will get sick and what they can do about it. Consortium on Metabonomic Toxicity Science: Smaller, simpler molecules like glucose, histamine, and nitric oxide play major roles in metabolic and other processes. They're also the most accessible window on body functions. Goal: Analyzing the level of small molecules in blood samples could show whether a patient has, for example, the beginnings of Alzheimer's or a bad reaction to a drug. Consortium labs are looking this year at the ways particularly toxic drugs can cause harm. – Monya Baker and Stacy Lawrence