Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.
Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.
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通过控制 Apoa2 等位基因效应在小鼠中鉴定出 HDL 水平的新 QTL：确认同源品系中的 6 号染色体位点。
DOI：
10.1152/physiolgenomics.00124.2003
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Lusis,AldonsJ
中科院分区：
文献类型：
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作者：
Welch,CarrieL;Bretschger,Sara;Wen,Ping-Zi;Mehrabian,Margarete;Latib,Nashat;Fruchart-Najib,Jamila;Fruchart,JeanCharles;Myrick,Christy;Lusis,AldonsJ
动脉粥样硬化是一种由多种基因相互作用引起的复杂疾病，包括导致血脂异常的基因。已确定的致病基因相对较少。此前，我们确定Apoa2是小鼠模型中高密度脂蛋白胆固醇（HDL-C）水平的主要决定因素。为了确定额外的 HDL-C 水平数量性状基因座 (QTL)，同时控制 Apoa2 基因座的影响，我们对源自品系 BALB/cJ 和 B6.C-H25c（携带 BALB/cApoa2 等位基因的同源品系）的 179 只标准饮食喂养的 F2 小鼠进行了连锁分析。鉴定出 3 个显着 QTL 和 1 个提示性基因座。映射到 6 号染色体 (Chr 6) 的女性特异性基因座也表现出对血浆非 HDL-C、载脂蛋白 AII (apoAII)、apoB 和 apoE 水平的影响。在相关同源菌株中独立分离出 Chr 6 QTL（C57BL/6J 与 B6.NODc6：HDL-C 和非 HDL-C 水平分别为 P= 0.003 和 P= 0.0001）。这些数据与小鼠模型中 HDL-C 水平的多基因遗传一致，并为人类 HDL-C 和非 HDL-C 水平测定提供了候选基因座。
Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identifiedApoa2as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of theApoa2locus, we performed linkage analysis in 179 standard diet-fed F2mice derived from strains BALB/cJ and B6.C-H25c(a congenic strain carrying the BALB/cApoa2allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6:P= 0.003 andP= 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.