CONSERVATION OF SYNTENY BETWEEN THE GENOME OF THE PUFFERFISH (FUGU-RUBRIPES) AND THE REGION ON HUMAN-CHROMOSOME-14 (14Q24.3) ASSOCIATED WITH FAMILIAL ALZHEIMER-DISEASE (AD3 LOCUS)

The genome of the pufferfish (Fugu rubripes) (400 Mb) is approximate t o 7.5 times smaller than the human genome, but it has a similar gene r epertoire to that of man, If regions of the two genomes exhibited cons ervation of gene order (i.e., were syntenic), it should be possible to reduce dramatically the effort required for identification of candida te genes in human disease loci by sequencing syntenic regions of the c ompact Fugu genome, We have demonstrated that three genes (dihydrolipo amide succinyltransferase, S31iii125, and S20i15), which are linked to FOS in the familial Alzheimer disease locus (AD3) on human chromosome 14, have homologues in the Fugu genome adjacent to Fugu cFOS, The rel ative gene order of cFOS, S31iii125, and S20i15 was the same in both g enomes, but in Fugu these three genes lay within a 12.4-kb region, com pared to >600 kb in the human AD3 locus, These results demonstrate the conservation of synteny between the genomes of Fugu and man and highl ight the utility of this approach for sequence-based identification of genes in human disease loci.