Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits
Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits
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DOI：
10.1016/j.cell.2012.08.012
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发表时间：
2012-09-14
期刊：
影响因子：
64.5
通讯作者：
Auwerx, Johan
中科院分区：
文献类型：
--
作者：
Andreux, Penelope A.;Williams, Evan G.;Auwerx, Johan
代谢稳态是通过复杂的分子和细胞网络来实现的，这些网络在个体之间存在显著差异，并且难以用经优化以研究单基因功能的基因工程小鼠系来建模。在这里，我们通过使用EUMODIC EMPReSS方案在一大批同基因但不同品系的小鼠（BXD型）中系统地获得代谢表型，以研究代谢的遗传控制。我们生成并分析了140个经典表型，并将其保存在系统遗传学开放访问的网络服务（www.genenetwork.org）中。利用数量性状基因座（QTL）和表达QTL定位方法，对性状的遗传力、性别影响和遗传修饰因子进行了单独和联合检测。性状和网络与包含已知变体和新候选基因的基因座相关，包括碱性磷酸酶（ALPL），此处与低磷酸酶症相关。组装和策划的表型提供了关键的资源和范例，可用于剖析复杂的代谢特征和疾病。
Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.