This is an incredible time for geneticists who only a decade ago looked at the human genome - the mammoth entirety of Homo sapiens' genetic blueprint - and began to decipher it. Amazingly, the worldwide initiative known as the Human Genome Project (HGP) is in the homestretch.
"We completed a rough draft of the entire genome this spring," said Susan L. Naylor, Ph.D., professor of cellular and structural biology at the Health Science Center and the faculty member who has been most involved with the HGP. "All data from the genome are in various databases such as ours and very soon will be assembled in the correct order to make a complete genome map."
The Health Science Center, in collaboration with other centers, will be known for playing a major role in ensuring that Human Chromosome 3 was "sequenced" - that the order of the genetic material in the chromosome was precisely revealed and catalogued. Chromosome 3, the third largest of the human chromosomes, accounts for 7 percent of a person's entire genetic blueprint. Increased knowledge of the genome is changing the face of disease prevention, diagnosis and treatment, and the revolution is just beginning.
"In our Health Science Center labs, we have proven that a gene on Chromosome 3 is linked to ovarian cancer," Dr. Naylor said. "We are working with many types of genes, including several that suppress formation of various cancers and others that are involved in bone development. Scientists worldwide come to us because we are the resource, the clearinghouse, for information on Chromosome 3."
The genome, composed of an amazing primordial acid called DNA, is found in the center of every cell. More complex than the most sophisticated computer software,
DNA programs the biology of development, puberty, adult life and death. It appears in structures, called chromosomes, located in the nucleus of every cell. DNA is made up of blocks of functional units called genes and contains four foundational amino acids, abbreviated as G, C, A and T. The order of these acids determines the very function of a sequence of DNA.
Dr. Naylor's lab provides "clones" (copies of DNA extracted from cells and grown in petri dishes) for two other centers that are sequencing Chromosome 3. She collaborates with Richard Gibbs, Ph.D., of the Baylor College of Medicine in Houston and Bob Waterston, Ph.D., of Washington University in St. Louis, Mo. When the sequence of a stretch of DNA is worked out, these centers ship the results to the Health Science Center for entry into its repository of information about Chromosome 3. San Antonio is the worldwide starting point and stopping place for almost all of the Chromosome 3 genetic findings.
Susan L. Naylor, Ph.D.,
professor of cellular and structural biology, is leading
the Health Science Center's participation in the worldwide
Human Genome Project.
"Think of the genome as a book, the chromosomes as chapters and genes as words," Dr. Naylor said. "The amino acids, G, C, A and T, are the letters of the words. To study this literary masterpiece, we scientists have pulled out the letters and are painstakingly putting the book back together. Our approach is to reconstruct the genome - and in our case, one chromosome - using letters we copied from the original prose," she said.
The book can be difficult to read. It contains repetitive DNA sequences that mystify researchers. During the Human Genome Project, Dr. Naylor and her colleagues around the world had to make sure that such sequences were not inserted in the wrong order in the reconstructed genome. Like librarians they pored over the collection; in fact, the entire genome has been sequenced four times to ensure accuracy, Dr. Naylor said.
The HGP scientists should reach a point of closure by 2003. "We'll be out of business, so to speak, but this effort is leading to new questions," she said. "For example, even though we have identified hundreds of genes, we still don't know how 90 percent of the genome works." Indeed, one of the next steps for scientists is to more clearly define and understand the three-dimensional structure of DNA.
"We are at an incredible point because there is such an explosion of knowledge," Dr. Naylor said. "This information is raising ethical questions faster than we can find answers. In some cases, physicians are able to predict whether someone will have a particular disease in the future. It's believed that everyone has at least three 'bad' genes, and cancer, heart disease, diabetes and all the diseases have huge genetic components. The amount of knowledge coming out now will keep us occupied for a long time."
Since science in the laboratory often presages clinical advancements, it's not unreasonable to think that one day, the Human Genome Project will be the foundation of dramatic clinical discoveries.