In the October 5 Science, Len Pennacchio and colleagues, at the Lawrence Berkeley National Laboratory in California, describe how interspecies sequence comparison of the human and mouse apolipoprotein gene cluster (APOAI/CIII/AIV) led to the identification of a novel apolipoprotein-like gene (APOAV)(Science 2001, 294:169-173). Transgenic mice overexpressing the human APOAV gene have reduced plasma triglyceride levels, whereas APOAV-deficient knockout animals had four-times higher levels than controls. Pennacchio et al. found that single nucleotide polymorphisms (SNPs) in the human APOAV gene were linked to changes in plasma triglyceride levels. Thus, APOAV polymorphisms may serve as prognostic indicators for hypertriglyceridemia susceptibility and cardiovascular disease risk. The authors emphasize that comparative sequence analysis was key to the identification of APOAV.