MOLECULAR-CLONING AND MAPPING OF HUMAN SEMAPHORIN-F FROM THE CRI-DU-CHAT CANDIDATE INTERVAL

Cri-du-chat is a human contiguous gene deletion syndrome resulting fro m hemizygous deletions of chromosome 5p. Here we describe the isolatio n from within this interval of the human Semaphorin F (SEMAF) gene, a member of a family of proteins that has been implicated in axonal path finding. The human SEMAF gene covers at least 10% of the deleted regio n and defines a new class within this large gene family characterized by the presence of seven type 1 thrombospondin repeats. Prominent expr ession of murine semaphorin F (Semaf) was observed in the mouse brain, consistent with a role for semaphorin F as a signaling molecule that guides axons or migrating neuronal precursors during development. The known functions of semaphorins and the interesting pattern of expressi on for Semaf suggest that haploinsufficiency for SEMAF may disrupt nor mal brain development and might lead to some of the features of Cri-du -chat. (C) 1998 Academic Press.