Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family

Hair keratin-associated proteins (KAP) are a major structural component of the hair fiber. In humans, five clusters of KAP genes have been identified, leading to the isolation of more than 80 individual KAP members. Of these, a cluster of high/ultrahigh sulfur KAP has been characterized on chromosome 17q12-21. Within this cluster, however, there was an incompletely sequenced region in which the ultrahigh sulfur KAP4 genes were located. A recently reported human bacterial artificial chromosome clone, AC100808, finally covered the gap, which enabled us to characterize the complete set of KAP4 genes in this cluster. Analysis of the nucleotide sequences of AC100808, together with PCR amplification, allowed us to identify numerous size polymorphisms in the KAP4 genes, which were mainly due to variations in the sequences encoding cysteine-rich repeat segments. Taken together, the data indicate that the polymorphic alleles of the KAP4 genes may have arisen through intragenic deletion and/or duplication of sequences encoding the repeat structures during evolution.