CDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family

The insertion of double bonds into specific positions of fatty acids is ach ieved by the action of distinct desaturase enzymes. Here we report the clon ing and characterization of three members of the fatty acid desaturase (FAD S) gene family in humans. Initially identified as cDNA fragments by direct cDNA selection within a defined 1.4-Mb region in 11q12-q13.1, full-length f atty acid desaturase-1 (FADS1) and fatty acid desaturase-2 (FADS2) transcri pts were obtained by EST sequence assembly. A third member, fatty acid desa turase-3 (FADS3), was identified in silico revealing 62 and 70% nucleotide sequence identity with FADS1 and FADS2, respectively. The three genes are c lustered within 92 kb of genomic DNA located 2 kb telomeric to FEN1 and 50 kb centromeric to VMD2 and are likely to have arisen evolutionarily from ge ne duplication as they share a remarkably similar exon/ intron organization . Protein database searches identified FADS1, FADS2, and FADS3 as fusion pr oducts composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion. (C) 2000 Academic Press.