Structural organization and genetic localization of the human bone morphogenetic protein 1/mammalian tolloid gene.

Bone morphogenetic protein 1 (BMP1) is a putative protease purified from extracts capable of inducing ectopic bone formation. A single mammalian gene apparently encodes alternatively spliced transcripts for BMP1, for a longer protein with a domain structure identical to that of the Drosophila dorsal-ventral patterning gene product tolloid (Tld), and for a third species of low abundance. Here we describe the organization of the 46-kb, 22-exon human BMP1/mTld gene that encodes these forms. Exons corresponding to each of the alternatively spliced transcripts are identified, and comparison with the Drosophila Tld gene reveals alignment of introns at only three positions. The major BMP1/mTld transcription start site is found only 706 bp downstream of the polyadenylation site of the SFTP2 surfactant gene, and a previously reported highly polymorphic CA repeat is found within the BMP1/mTld first intron. These two findings place the BMP1/mTld gene between markers D8S298 and D8S5 on the genetic map.