A YEAST ARTIFICIAL CHROMOSOME CONTIG OF THE CRITICAL REGION FOR CRI-DU-CHAT SYNDROME

Cri-du-chat is a chromosomal deletion syndrome characterized by partia l deletion of the short arm of chromosome 5. The clinical symptoms inc lude growth and mental retardation, microcephaly, hypertelorism, epica nthal folds, hypotonia, and a high-pitched monochromatic cry that is u sually considered diagnostic for the syndrome. Recently, a correlation between clinical features and the extent of the chromosome 5 deletion s has identified two regions of the short arm that appear to be critic al for the abnormal development manifested in this syndrome. Loss of a small region in 5p15.2 correlates with all of the clinical features o f cri-du-chat with the exception of the cat-like cry, which maps to 5p 15.3. Here we report the construction of a YAC contig that spans the c hromosomal region in 5p15.2 that plays a major role in the etiology of the cri-duchat syndrome. YACs that span the 2-Mb cri-du-chat critical region have been identified and characterized. This YAC contig lays t he groundwork for the construction of a transcriptional map of this re gion and the eventual identification of genes involved in the clinical features associated with the cri-du-chat syndrome. It also provides a new diagnostic tool for cri-du-chat in the shape of a YAC clone that may span the entire critical region. (C) 1994 Academic Press, Inc.