DIRECT SELECTION OF CONSERVED CDNAS FROM THE DIGEORGE CRITICAL REGION- ISOLATION OF A NOVEL CDC45-LIKE GENE

We have used a modified direct selection technique to detect transcrip ts that are both evolutionary conserved and developmentally expressed. The enrichment for homologous mouse cDNAs by use of human genomic DNA as template is shown to be an efficient and rapid approach for genera ting transcript maps. Deletions of human 22q11 are associated with sev eral clinical syndromes, with overlapping phenotypes, for example, vel ocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS). A large num ber of transcriptional units exist within the defined critical region, many of which have been identified previously by direct selection. Ho wever, no single obvious candidate gene for the VCFS/DGS phenotype has yet been found. Our technique has been applied to the DiGeorge critic al region and has resulted in the isolation of a novel candidate gene, Cdc4512, similar to yeast Cdc45p.