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.