HUMAN UTEROGLOBIN GENE - STRUCTURE, SUBCHROMOSOMAL LOCALIZATION, AND POLYMORPHISM

Human uteroglobin (hUG) or Clara cell 10-kD protein (cc10 kDa) is a st eroid-dependent, immunomodulatory, cytokine-like protein, It is secret ed by mucosal epithelial cells of all vertebrates studied, The cDNA en coding hUG and the 5' promoter region of the gene have been characteri zed previously, Here, we report that the structure of the entire hUG g ene is virtually identical to those of rabbit, rat, and mouse, It is l ocalized on human chromosome 11q12.3-13.1, a region in which several i mportant candidate disease genes have been mapped by linkage analyses, Our data indicate that candidate genes for atopic (allergic) asthma a nd Best's vitelliform macular dystrophy are in closest proximity to th e hUG gene, To determine whether hUG gene mutation may be involved in the pathogenesis of these diseases, we studied two isolated groups of patients, each afflicted with either atopy or Best's disease, respecti vely, We detected a single base-pair change in the hUG gene in Best's disease patients and normal controls but no such change was detected i n atopy patients, This alteration in hUG gene-sequence in Best disease family appears to be a polymorphism, Although the results of our inve stigation did not uncover mutations in hUG gene that could be causally related to the pathogenesis of either of these diseases, its conserva tion throughout vertebrate phyla implies that this gene is of physiolo gical importance, Moreover, the close proximity of this gene to severa l candidate disease genes makes it an important chromosomal marker in cloning and characterization of those genes.