Gatti Daniel, Maki Akira, Chesler Elissa J, Kirova Roumyana, Kosyk Oksana, Lu Lu, Manly Kenneth F, Williams Robert W, Perkins Andy, Langston Michael A, Threadgill David W, Rusyn Ivan
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Hepatology. 2007 Aug;46(2):548-57. doi: 10.1002/hep.21682.
The liver is the primary site for the metabolism of nutrients, drugs, and chemical agents. Although metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variations in gene expression levels, introduces complexity into research on liver disease. This study dissected genetic networks that control liver gene expression through the combination of large-scale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive single-nucleotide polymorphism, haplotype, and phenotypic data are publicly available. We profiled gene expression in livers of naive mice of both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent oligonucleotide microarrays. These data were used to map quantitative trait loci (QTLs) responsible for variations in the expression of about 19,000 transcripts. We identified polymorphic local and distant QTLs, including several loci that control the expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL.
The data are available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of coregulated transcripts and correlated phenotypes, cross-tissue, and cross-species comparisons, as well as testing of a broad array of hypotheses.
肝脏是营养物质、药物和化学物质代谢的主要场所。尽管代谢途径复杂且受到严格调控，但个体间的基因变异，反映在基因表达水平的差异上，给肝病研究带来了复杂性。本研究通过将大规模定量mRNA表达分析与基因定位相结合，剖析了控制肝脏基因表达的遗传网络，研究对象是BXD重组近交小鼠品系的参考群体，该群体有广泛的单核苷酸多态性、单倍型和表型数据可供公开获取。我们使用安捷伦寡核苷酸微阵列对来自C57BL/6J、DBA/2J、B6D2F1和37个BXD品系的雌雄未处理小鼠肝脏中的基因表达进行了分析。这些数据用于定位负责约19,000个转录本表达变异的数量性状基因座（QTL）。通过比较物理转录本位置与控制QTL的位置，我们鉴定出了多态性的局部和远距离QTL，包括几个控制肝脏中大量基因表达的基因座。
这些数据可通过基于网络的公共资源（www.genenetwork.org）获取，该资源允许进行定制数据挖掘、鉴定共调控转录本和相关表型、跨组织和跨物种比较，以及对广泛的假设进行检验。
