Farber Charles R, Aten Jason E, Farber Emily A, de Vera Vincent, Gularte Rodrigo, Islas-Trejo Alma, Wen Pengzi, Horvath Steve, Lucero Michael, Lusis Aldons J, Medrano Juan F
Department of Medicine, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Physiol Genomics. 2009 May 13;37(3):294-302. doi: 10.1152/physiolgenomics.90245.2008. Epub 2009 Mar 31.
HG.CAST-(D9Mit249-D9Mit133) (HG9) congenic mice are homozygous for CAST/EiJ chromosome (Chr) 9 alleles from approximately 9 to 84 Mbp on a C57BL6/J-hg/hg (HG) background. This region contains the carcass fat in high growth mice (Carfhg2) quantitative trait locus (QTL), and while its obesity-promoting effects have been confirmed in HG9 mice, its underlying genetic basis remains elusive. To refine the location of Carfhg2, we preformed a linkage analysis in two congenic F2 intercrosses and progeny-tested a recombinant F2 male. These analyses narrowed Carfhg2 to between 33.0 and 40.8 Mbp on Chr 9. To identify candidate genes we measured the expression of 44 transcripts surrounding the Carfhg2 peak in adipose, brain, liver, and muscle tissues from F2 mice using Biomark 48.48 Dynamic Arrays. In total, 68% (30 of the 44) of genes were regulated by a significant expression QTL (eQTL) in at least one tissue. To prioritize genes with eQTL we used Network Edge Orienting, a causality modeling tool. These analyses advance our goal of identifying the molecular basis of Carfhg2.
HG.CAST-(D9Mit249-D9Mit133) (HG9) 同源基因小鼠在C57BL6/J-hg/hg (HG) 背景下，对于CAST/EiJ 9号染色体（Chr）上约9至84 Mbp的等位基因是纯合的。该区域包含高生长小鼠的胴体脂肪（Carfhg2）数量性状基因座（QTL），虽然其促进肥胖的作用已在HG9小鼠中得到证实，但其潜在的遗传基础仍然难以捉摸。为了细化Carfhg2的定位，我们在两个同源F2杂交中进行了连锁分析，并对一只重组F2雄性小鼠进行了后代测试。这些分析将Carfhg2定位在9号染色体上33.0至40.8 Mbp之间。为了鉴定候选基因，我们使用Biomark 48.48动态阵列测量了F2小鼠脂肪、脑、肝和肌肉组织中围绕Carfhg2峰值的44个转录本的表达。总共，68%（44个中的30个）的基因在至少一种组织中受到显著表达数量性状基因座（eQTL）的调控。为了对具有eQTL的基因进行优先级排序，我们使用了因果关系建模工具Network Edge Orienting。这些分析推进了我们确定Carfhg2分子基础的目标。
