Fly (F), worm (W), and yeast (Y) genes showing similarity to human disease genes. This collection of human disease genes was selected to represent a cross section of human pathophysiology and is not comprehensive. The selection criteria require that the gene is actually mutated, altered, amplified, or deleted in a human disease, as opposed to having a function deduced from experiments on model organisms or in cell culture. Due to redundancy in gene and protein sequence databases, a single reference sequence for each gene had to be chosen. Most reference sequences represent the longest mRNA of several alternatives in GenBank. Authoritative sources in the literature and electronic databases [Online Mendelian Inheritance in Man (OMIM)] were also consulted. In all, 289 protein sequences met these criteria. These were used as queries to search a database consisting of the sum total of gene products (38,860) found in the complete genomes of fly, worm, and yeast. 12,953 was used as the effective database size (the z parameter in BLAST). BLASTP searches were conducted as described for full genome searches, except for the z parameter. To control for potential frameshift errors in the Drosophila genome sequence, searches against a six-frame translation of the entire genome (using TBLASTN) were also conducted with the disease gene sequences using the z parameter above. Only two cases in which matches to genomic sequence were better than to the predicted protein were found, and these were manually corrected to reflect the better TBLASTN scores in the table. Results are scaled according to various levels of statistical significance, reflecting a level of confidence in either evolutionary homology or functional similarity. White boxes represent BLAST E values >1 × 10−6, indicating no or weak similarity; light blue boxes represent E values in the range of 1 × 10−6 to 1 × 10−40; purple boxes represent E values in the range of 1 × 10−40 to 1 × 10−100; and dark blue boxes represent E values <1 × 10−100, indicating the highest degree of sequence conservation. Actual E values can be found in the Web supplement to this figure (62), where links to OMIM and GenBank may also be found. A plus sign indicates our best estimate that the corresponding Drosophila gene product is the functional equivalent of the human protein, based on degree of sequence similarity, InterPro domain composition, and supporting biological evidence, when available. A minus sign indicates that we were unable to identify a likely functional equivalent of the human protein.