IDENTIFICATION OF THE MURINE BEIGE GENE BY YAC COMPLEMENTATION AND POSITIONAL CLONING

The beige mutation is a murine autosomal recessive disorder, resulting in hypopigmentation, bleeding and immune cell dysfunction. The gene d efective in beige is thought to be a homologue of the gene for the hum an disorder Chediak-Higashi syndrome. We have identified the murine be ige gene by in vitro complementation and positional cloning, and confi rmed its identification by defining mutations in two independent mutan t alleles. The sequence of the beige gene message shows strong nucleot ide homology to multiple human ESTs, one or more of which may be assoc iated with the Chediak-Higashi syndrome gene. The amino acid sequence of the Beige protein revealed a novel protein with significant amino a cid homology to orphan proteins identified in Saccharomyces cerevisiae , Caenorhabditis elegans and humans.