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, approximately 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.
Rollins
Jarod
J
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Chen
Yaoyu
Y
Paigen
Beverly
B
Wang
Xiaosong
X
D000818:Animals; D002874:Chromosome Mapping; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D023281:Genomics; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics*; D051379:Mice; D040641:Quantitative Trait Loci / Q000235:genetics
D008075:Lipoproteins, HDL