ISOLATION AND CHROMOSOMAL MAPPING OF GENOMIC CLONES ENCODING THE HUMAN FATTY-ACID SYNTHASE GENE

We have isolated and sequenced 0.5- and 3.6-kb cDNA clones that cover the N-terminal and carboxy-terminal regions, respectively, of the huma n fatty acid synthase. To localize the fatty acid synthase gene and to define its genomic structure, we have also isolated overlapping genom ic clones by screening two human YAC libraries with PCR primers derive d from the fatty acid synthase cDNA sequences. The DNA inserts in thes e human fatty acid synthase YACs hybridized with human synthase-specif ic cDNA probes. Using biotin-labeled ALu-PCR products of the human syn thase YACs as probes for fluorescence in situ hybridization, we mapped the fatty acid synthase gene to chromosome 17q25. We also screened a chromosome 17-specific cosmid library with human synthase cDNA probes and isolated 12 cosmids, all of which had EcoRI fragments in common. D NA sequencing of an amplified PCR product from the fatty acid synthase cosmids confirmed that these genomic clones contained expressed fatty acid synthase sequences. Furthermore, the results of Southern analyse s suggested that a single 40-kb cosmid clone encompasses the entire co ding region of the fatty acid synthase gene. The synthase gene is loca ted on chromosome 17 near the q25 band, which is close to the telomere and could serve as an important marker in analysis of this chromosome . (C) 1994 Academic Press, Inc.