CLONING, EXPRESSION, AND CHROMOSOMAL LOCATION OF SHH AND IHH - 2 HUMAN HOMOLOGS OF THE DROSOPHILA SEGMENT POLARITY GENE HEDGEHOG

The hedgehog genes encode signaling molecules that play a role in regu lating embryonic morphogenesis, We have cloned and sequenced human cDN A copies of two of these genes, SHH and IHH. The SHH clone includes th e full coding sequence and encodes a protein 92.4% identical to its mu rine homologue, The IHH clone is 89% complete and encodes a protein 94 .6% identical to its murine homologue. IHH is expressed in adult kidne y and liver. SHH expression was not detected in adult tissues examined ; however, it is expressed in fetal intestine, liver, lung, and kidney . SHH mapped to chromosome 7q and IHH to chromosome 2 by PCR with DNA from a panel of rodent-human somatic cell hybrids. To identify the chr omosomal location of SHH more precisely, a pi genomic clone of SHH was isolated. This phage contained a CA repeat sequence tagged site that was used to map SHH relative to a polysyndactyly disease locus, using DNA prepared from affected and unaffected members of a large pedigree, SHH is closely linked, but distinct from the polysyndactyly disease l ocus at 7q36 (maximum lod score = 4.82, theta = 0.05) tightly linked t o the EN2 locus, The murine homologues Shh, Ihh, and Dhh were mapped u sing (C57BL/6J x Mus spretus)F-1 x C57BL/6J interspecific backcross. S hh mapped to a position 0.6 cM distal to En2 and 1.9 cM proximal to Il 6 on mouse chromosome 5. This location is closely linked but distinct from the murine limb mutation Hx and syntenic to human chromosome 7q36 . (C) 1995 Academic Press, Inc.