Rollins Jarod, Chen Yaoyu, Paigen Beverly, Wang Xiaosong
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Trends Cardiovasc Med. 2006 Oct;16(7):220-34. doi: 10.1016/j.tcm.2006.04.003.
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.
多项证据表明，提高血浆高密度脂蛋白胆固醇（HDL-C）水平可能抑制甚至逆转动脉粥样硬化。人类和小鼠均已进行数量性状基因座（QTL）分析。到目前为止，每个物种中已鉴定出约40个调节高密度脂蛋白（HDL）的QTL。为了比较人类和小鼠的HDL-C QTL，我们基于人类和小鼠的同源基因生成了人类-小鼠比较染色体图谱。比较图谱显示，大多数人类和小鼠的HDL-C QTL是一致的，这表明在小鼠中鉴定潜在的QTL基因将有助于在人类中鉴定其同源物。这些图谱还通过小鼠-人类同源QTL比较有助于缩小QTL范围。通过结合经典遗传学方法和更新的生物信息学工具（包括本研究中强调的比较基因组学），确定血浆HDL-C水平的新药物靶点比以往更具前景。
