A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster

We performed a systematic BLAST analysis of 929 human disease gene entries associated with at least one mutant allele in the Online Mendelian Inherita nce in Man (OMIM) database against the recently completed genome sequence o f Drosophila melanogaster. The results of this search have been Formatted a s an updateable and searchable on-line database called Homophila. Our analy sis identified 714 distinct human disease genes (77% of disease genes searc hed) matching 548 unique Drosophila sequences, which we have summarized by disease category. This breakdown into disease classes creates a picture of disease genes that are amenable to study using Drosophila as the model orga nism. Of the 548 Drosophila genes related to human disease genes, 153 are a ssociated with known mutant alleles and 56 more are tagged by P-element ins ertions in or near the gene. Examples of how to use the database to identif y Drosophila genes related to human disease genes are presented. We anticip ate that cross-genomic analysis of human disease genes using the power of D rosophila second-site modifier screens will promote interaction between hum an and Drosophila research groups, accelerating the understanding of the pa thogenesis of human genetic disease. The Homophila database is available at http://homophila.sdsc.edu.