Defensins are a large family of host defense peptides expressed in leukocyt
es and epithelia. Using P1 and BAC clones, we have determined the organizat
ion 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 pe
ptides in parentheses) is HDEFA5 (HD-5), HDEFA1/A (HNP-1/3), HDEFA4 (HNP-4)
, HDEFA6 (HD-6), and HDEFB1 (HBD-1). These genes span a region of approxima
tely 450 kb. Genes encoding intestinal Paneth cell defensins (HDEFA5 and HD
EFA6) flank the myeloid defensin gene cluster (HDEFA1, HDEFA1A, HDEFA4). Ba
sed on our previous studies, the remaining known defensin gene, HDEFB2 (HBD
-2), is about 400 kb centromeric to HDEFB1. This map supports the hypothesi
s, originally proposed because of sequence similarities, that myeloid alpha
-defensin genes evolved by reduplication and divergence from Paneth cell de
fensin genes, and identifies regions and clones, which should be useful in
the search for new defensin genes. (C) 1999 Elsevier Science B.V. All right
s reserved.