ORGANIZATION OF THE HUMAN KERATIN TYPE-II GENE-CLUSTER AT 12Q13

Keratin proteins constitute intermediate filaments and are the major d ifferentiation products of mammalian epithelial cells. The epithelial keratins are classified into two groups, type I and type II and one me mber of each group is expressed in a given epithelial cell differentia tion stage. Mutations in type I and type II keratin genes have now bee n implicated in three different human genetic disorders, epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic palm oplantar keratoderma Members of the type I keratins are mapped to huma n chromosome 17, and the type II keratin genes are mapped to chromosom e 12. To understand the organization of the type II keratin genes on c hromosome 12, we isolated several yeast artificial chromosomes carryin g these keratin genes and examined them in detail. We show that eight already known type II keratin genes are located in a cluster at 12q13, and their relative organization reflects their evolutionary relations hip. We also determined that a type I keratin gene, KRT18, is located next to its partner, KRT8, in this cluster. Careful examination of the cluster also revealed that there may be a number of additional kerati n genes at this locus that have not been described previously. (C) 199 4 Academic Press,Inc.