The purpose of this research project is to study, at the molecular level, the most common human deletion syndrome known, cri du chat. These studies will include defining, using recombinant DNA probes, the precise region on the short arm of chromosome 5 that is responsible, when deleted, for producing the clinical and phenotypic symptoms of the cri du chat syndrome. Once such a region is defined at the DNA level, we will attempt to identify the products (RNA transcripts and/or their polypeptide translation products) of the genes localized to this phenotypically relevant segment of the short arm of chromosome 5. In addition, in various persons with cri du chat syndrome in which the deleted chromosome has arisen de novo, we will determine whether the deleted chromosome is of paternal or maternal origin. At present, it is not possible to perform these kinds of analyses for any human deletion syndrome. The project utilizes a combination of somatic cell genetic and recombinant DNA technologies. The system we have established to study this disorder enables us to isolate, in interspecific somatic cell hybrids, altered chromosome 5 derivatives from persons with various deletions of this chromosome. This allows us to study the altered chromosome 5's, and DNA sequence deleted from them, apart from the normal chromosome 5 homolog present in cells from such persons. Futhermore, we have a recombinant genomic DNA library that is specific for the short arm of human chromosome 5, which will allow us to identify and localize unique DNA sequences to specific regions of this part of the human genome, including the region relevant to producing the symptoms of the cri du chat syndrome when it is deleted. This system provides a unique opportunity to gain a wealth of information about the most common human deletion syndrome and to study a complex biological and medical problem at a level that has not heretofore been possible.
