STRUCTURE, CHROMOSOMAL LOCATION, AND EXPRESSION PROFILE OF EXTR1 AND EXTR2, NEW MEMBERS OF THE MULTIPLE EXOSTOSES GENE FAMILY

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterized by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses. Genetical heterogeneities h ave segregated at least on chromosome 8, 11, and 19 and been designate d EXT1, EXT2, and EXT3, respectively. Recently, the responsible genes for EXT1 and EXT2 have been isolated and appeared to define a structur ally related gene family. In the present study, we have identified nov el genes which share significant sequence homologies with the EXT gene s. The predicted protein products of the novel EXT-related genes, EXTR 1 and EXTR2 (for EXT-related genes 1 and 2), consist of 919 and 330 am ino acid residues, respectively. These genes were transcribed ubiquito usly in various tissues. Based on PCR-assisted analyses of both a huma n/rodent mono-chromosomal hybrid cell panel and a radiation hybrid map ping panel, EXTR1 was localized to the chromosome 8p21 region, where l oss of heterozygosity has been frequently observed in various tumors, and EXTR2 was assigned to the chromosome 1p21 region, where osteopetro sis, a dominant hereditary disease of bone, has been mapped by genetic linkage analysis, implying that the protein products of these two EXT -related genes, as well as of the EXT genes, have potential tumor supp ressor activity. (C) 1998 Academic Press.