A GENETIC ALGORITHM FOR DESIGNING GENE FAMILY-SPECIFIC OLIGONUCLEOTIDE SETS USED FOR HYBRIDIZATION - THE G-PROTEIN-COUPLED RECEPTOR PROTEINSUPERFAMILY

Motivation: Massive oligonucleotide hybridization is one of the most p romising technologies of functional genome analysis. The critical poin t is to design appropriate sets of oligonucleotides that can be used e ffectively in identification by hybridization. Results: Using a generi c algorithm approach, Mle hate attempted to design sets of oligo probe s capable of identifying new genes belonging to a defined gene family within a cDNA or genomic library. Ir is not limited by oligonucleotide length and admits the letter 'N' in the structure of the oligonucleot ides selected. One of the major advantages of this approach is the low homology required to identify functional families of sequences with l ittle homology. We have designed the oligonucleotide sets that are mos t selective for the cDNA clones of transmembrane G protein-coupled rec eptors (GPCRs), a large family of proteins that form? part of a modula r system of extracellular signal transduction to the intracellular sec ond messenger pathways. The accuracy of identification has been checke d on the EST library containing 713 870 cDNA sequences. A set of 15 ol igos between 7 and 14 bases in length has correctly identified 70% of the GPCR cDNA collection sequences with 0.02% Salse positives.