A University of Colorado at Boulder research team has completed a two-year mapping project of a human chromosome associated with various diseases as part of the international Human Genome Project.
Led by Professor Ken Krauter of the molecular, cellular and developmental biology department, the groupÂ’s map of chromosome 18 includes genes involved in colorectal cancer, pancreatic cancer, breast cancer, non-Hodgkin lymphoma, bipolar disorder and Nieman-Pick disease Type C, a neurological disorder.
“Our map is useful for cloning genes involved in disease and for diagnosing genetic diseases,” said Krauter. “Its applications for sequencing the chromosome are its most valuable aspect.”
The team presented its integrated physical map of human chromosome 18 at a national genome project meeting May 14-18 in Cold Spring Harbor, N.Y. Other team members are graduate student Deborah McDonough, research assistants Christie Friesen and Katie Lord, and research associate Alla Karnovsky.
Although various Colorado research groups are involved in the Human Genome Project, the ¶¶ÒõÂÃÐÐÉä-Boulder team is only the second in the state to map an entire chromosome. A team from ¶¶ÒõÂÃÐÐÉäÂ’s Health Sciences Center produced a map of chromosome 3 several years ago. The human body contains 23 chromosome pairs.
The genetic material in chromosomes, DNA, contains subunits called bases which, when strung together, form the genetic code. One of the goals of the Human Genome Project is to determine the complete sequence of bases comprising the DNA of each chromosome.
Maps like the one created by KrauterÂ’s group are precursors to sequencing a chromosome, said Krauter. Chromosome 18 contains about 80 million bases, but current techniques allow for sequencing only a few hundred bases at once.
To make human DNA manageable, a library of DNA clones was created by cutting human DNA into thousands of pieces and inserting them into yeast cells. The human DNA can then easily be replicated and manipulated.
Known sequences of DNA unique to chromosome 18 were used as markers and a technique called the polymerase chain reaction was used to locate these unique sequences in the DNA clones. Using powerful computer programs, the ¶¶ÒõÂÃÐÐÉä researchers determined the order of the markers and clones along the chromosome.
The next step is to correlate each DNA clone into several smaller, bacterially based clones that can be sequenced directly, said Krauter. Since the order of the clones is known, they can be sequenced individually and then strung together to form the sequence of the entire chromosome.
The international Human Genome Project was launched in October 1990 to discover and characterize all of the estimated 60,000 to 100,000 genes in the human genome. The project is directed jointly by the Department of Energy, the National Institutes of Health the National Center for Human Genome Research.
The Internet has played an integral role in the genome project, allowing data to be quickly updated and shared among researchers, said Krauter. By accessing information from other research teams electronically, KrauterÂ’s group was able to integrate many types of data into their map, adding to its confidence level.
At the current rate of progress, the Human Genome Project could be completed as early as 2002 -- three years ahead of schedule, said the researchers.
“The Human Genome Project will allow us to design new therapies for genetic diseases through understanding the mechanisms of disease,” said Krauter. “It also will aid our understanding of how humans develop and how multigene traits like behavior, hypertension and metabolic diseases are amenable to understanding through genetic analysis.”