Special Problems of Polymorphisms

Abstract

DR. RAY WHITE: The real objective of the recombinant DNA endeavor is to identify a segment of DNA which contains the gene of interest. Our approach uses arbitrary loci and linkage analysis because with many genetic diseases, specifically including Duchenne and the other muscular dystrophies, that is the best one can do at this point. I think the comments with respect to a need for a specific cell phenotype in order to define a DNA segment as having a specific genetic content are very much to the point. It may be possible to precisely locate a gene by deletion to saturate the region about a gene and hope to find something, although it does strike me as a rather difficult task. I must say, however, that the deletion that Dr. Francke found in Xp21 is intriguing. We are interested in that kind of approach to retinoblastoma. A consequence of having a gene as a probe doesn’t mean that you give up looking for polymorphism and genetic markers. It just means that the quality of the genetic markers you get is much better. The recombination frequencies between the β-globin, for example, and the Hpa I site should be very small. No one has yet observed a recombinant despite about 1000 tests. The reason for isolating the gene is not to develop such a marker but to work out the molecular mechanism of the disease.