June 29, 1998 DALLAS, Texas, June 23, 1998 -- A computer program recently developed at UT Southwestern Medical Center at Dallas has found the markers on all DNA sequenced so far in the international Human Genome Project, and the list is now available on the Internet.
A UT Southwestern study, which developed and validated the computer code known as POMPOUS, is described in today's issue of Proceedings of the National Academy of Sciences. Markers are small bits of deoxyribonucleic acid (DNA) that can vary among individuals but are usually inherited within related groups. Differences in markers are called polymorphisms, and they can alter how a gene affects the body. The markers are used in identifying diseases, predicting risk of disease and in forensics investigations.
"Because of all the information coming out of the genome project, there needs to be more and more effort in computational biology to extract value from the raw DNA sequences and relate it to the function of the 100,000 or so genes and all the medical implications of the variations in each gene," said senior author Dr. Harold "Skip" Garner, associate director of UT Southwestern's federally funded Genome Science and Technology Center and holder of the Philip O'Bryan Montgomery Jr., M.D., Distinguished Chair in Developmental Biology. "Our system facilitates the step between genomic sequencing and using the data to discover the impact of genes on the quality of life."
In a collaborative effort with Dr. John Minna -- director of the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research and the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics and holder of the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology, the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Lisa K. Simmons Distinguished Chair in Comprehensive Oncology -- the researchers applied POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) to a 750,000 base pair region on human chromosome 3P. Minna used this section of DNA to study small-cell lung carcinoma, one of the deadliest forms of cancer.
"We ran the code on this region, identified about 40 markers and tested them," said Garner, co-director of the Biomedical Inventions Center. "Then Dr. Minna used the markers that the computer predicted in his research. It accelerated his ability to analyze and identify the genes and the properties of the sequence region."
In the verification process the computer accurately predicted the markers 67 percent of the time. Garner said this development significantly enhances the discovery of gene function. In addition it costs only about $20 to $40 to find a marker using this method.
"Using a parallel supercomputer on loan from Hewlett-Packard, we have pre-calculated the markers in all the genes that have been sequenced thus far so we have a list of 13,000 to 14,0000 markers on our Web site; we basically are giving them away to the world," he said. "We also put a server on the Web site so that anyone can submit their own sequence, and the code will predict the marker and hand them back oligonucleotide sequences ( bits of DNA used to identify genes) pre-designed for the laboratory technician to test the sequence in the lab."
Other UT Southwestern researchers involved in the study were cell and molecular biology graduate student John Fondon; Hamon Center research assistant Gina Mele; Hamon Center postdoctoral fellow Dr. Ruth Brezinschek; a UT Southwestern Science Teachers' Access to Resources at Southwestern (STARS) researcher Donna Cummings; Eugene McDermott Center for Human Growth and Development graduate student Jonathan Wren; surgery student research assistant Ashwini Pande; McDermott Center postdoctoral fellow Dr. Kevin O'Brien; and McDermott Center senior research scientist, Kenneth Kupfer. Drs. Ming-Hui Wei and Michael Lerman of the Laboratory of Immunobiology at the National Cancer Center in Frederick, Md., were also part of the study group.
The research was supported by grants from the Whitaker Foundation, the National Cancer Institute, Specialized Program of Research Excellence (SPORE) in Lung Cancer, Texas ARP (Advanced Research Projects) and the G. Harold and Leila T. Mathers Charitable Foundation.
The list of markers is available at http://POMPOUS.swmed.edu/.
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