A 450-kb contig of defensin genes on human chromosome 8p23

Defensins are a large family of host defense peptides expressed in leukocytes and epithelia. Using P1 and BAC clones, we have determined the organization of the human alpha-defensin genes and the beta-defensin gene HDEFB1 on chromosome 8p23. From the telomere, the order of the genes (with encoded peptides in parentheses) is HDEFA5 (HD-5), HDEFA1/1A (HNP-1/3), HDEFA4 (HNP-4), HDEFA6 (HD-6), and HDEFB1 (HBD-1). These genes span a region of approximately 450kb. Genes encoding intestinal Paneth cell defensins (HDEFA5 and HDEFA6) flank the myeloid defensin gene cluster (HDEFA1, HDEFA1A, HDEFA4). Based on our previous studies, the remaining known defensin gene, HDEFB2 (HBD-2), is about 400kb centromeric to HDEFB1. This map supports the hypothesis, originally proposed because of sequence similarities, that myeloid alpha-defensin genes evolved by reduplication and divergence from Paneth cell defensin genes, and identifies regions and clones, which should be useful in the search for new defensin genes.