In Search of New Targets for Plasma High-Density Lipoprotein Cholesterol Levels: Promise of Human–Mouse Comparative Genomics

Many lines of evidence suggest that raising plasma high-density lipoprotein cholesterol (HDL-C) levels may inhibit, perhaps even reverse, atherosclerosis. Quantitative trait locus (QTL) analysis has been performed in both humans and mice. So far, ∼40 high-density lipoprotein (HDL)-regulating QTLs have been identified in each species. To compare human and mouse HDL-C QTLs, we generate human–mouse comparative chromosome maps based on homologous genes in humans and mice. The comparative maps reveal that most human and mouse HDL-C QTLs are concordant, which suggests that identifying the underlying QTL genes in mice will facilitate identifying their homologs in humans. The maps also help to narrow QTLs by mouse–human homologous QTL comparison. By using a combination of classic genetic approaches and newer bioinformatics tools (including comparative genomics as highlighted in this study), identifying new drug targets for plasma HDL-C levels holds more promise than ever.