Recorded: 14 May 2004
Well, the problem was that we had a genetic disease which had pretty clear evidence that—unambiguous evidence—it was a single gene defect. And the phenotype for the most part was pretty clear as well. It was a very penetrant disease, the Lesch-Nyhan syndrome. And these children had devastating self-mutilation and profound mental retardation and short lives. But there is a milder form of the disease. And we really didn’t know if there was some subtle interplay between the mutational spectra in the gene and just how the phenotype unfolded.
And as well, there is so little known about the kind of mutations that caused human disease at that time that we wanted to establish some general rules about mutational spectra and the human phenotype. So that was the challenge; to figure out what exact changes were in these patients.
So when some of these molecular tests improved and we were able to take some of the methods and modify them and apply them and extract the nature of these changes in these genes in these patients, we were able to discover something about the correlation between the gene changes and the phenotype. Mostly what we found out was how the DNA worked, what things in the sequence would predispose it to certain types of mutations. But they were able, I think, for the first time to really get a handle on this connection between human variant gene sequence and this disease phenotype.
Richard A. Gibbs is currently the Director of the Human Genome Sequencing Center at Baylor College of Medicine (BCM) and the Wofford Cain Professor in the Department of Molecular and Human Genetics. He received a B.Sc. (Hons) in 1979 and a Ph.D. in Genetics and Radiation Biology in 1985 at the University of Melbourne in Australia. In 1990 he completed a postdoctoral fellowship at Houston’s Baylor College of Medicine, studying the molecular basis of human X-linked diseases and developing technologies for rapid genetic analysis. He developed several fundamental technologies for nucleic acid analysis. In 1991, he joined the BCM faculty and played a key role in the early planning and development phases of the Human Genome Project. In 1996, he established the BCM Human Genome Sequencing Center when Baylor was chosen as one of six programs to complete the final phase of the Human Genome Project. Dr. Gibbs has also made significant contributions to the deciphering of the fly, mouse, dictyostelium, and rat genomes. Among the numerous awards and honors received by Dr. Gibbs, he was awarded the Michael E. DeBakey, M.D., Excellence in Research Award in 2000.