THE HUMAN OBESE (OB) GENE - RNA EXPRESSION PATTERN AND MAPPING ON THEPHYSICAL, CYTOGENETIC, AND GENETIC MAPS OF CHROMOSOME-7

The recently identified mouse obese [ob] gene apparently encodes a sec reted protein that may function in the signaling pathway of adipose ti ssue. Mutations in the mouse ob gene are associated with the early dev elopment of gross obesity. A detailed knowledge concerning the RNA exp ression pattern and precise genomic location of the human homolog, the OB gene, would facilitate examination of the role of this gene in the inheritance of human obesity. Northern blot analysis revealed that OB RNA is present at a high level in adipose tissue but at much lower le vels in placenta and heart. OB RNA is undetectable in a wide range of other tissues. Comparative mapping of mouse and human DNA indicated th at the ob gene is located within a region of mouse chromosome 6 that i s homologous to a portion of human chromosome 7q. We mapped the human OB gene on a yeast artificial chromosome [YAC] contig from chromosome 7q31.3 that contains 43 clones and 19 sequence-tagged sites [STSs]. Am ong the 19 STSs are eight corresponding to microsatellite-type genetic markers, including seven [CA](n) repeat-type Genethon markers. Becaus e of their close physical proximity to the human OB gene, these eight genetic markers represent valuable tools for analyzing families with e vidence of hereditary obesity and for investigating the possible assoc iation between OB mutations and human obesity.