Jones Byron C, Jellen Leslie C
Department of Genetics, Genomics, and Informatics, The University of Tennessee Health Science Center, 410J Translational Research, 71 South Manassas St., Memphis, TN, 38163, USA.
Methods Mol Biol. 2017;1488:467-480. doi: 10.1007/978-1-4939-6427-7_22.
In this contribution, we demonstrate the utility of the systems genetics-systems biology approach to the study of iron regulation while employing a comprehensive database. We describe our work in iron regulation in the brain and periphery under normal iron and iron-restricted dietary conditions in the BXD family of recombinant inbred mouse strains. Using multiple measures, we showed wide variation among the strains in the effect of being fed an iron-restricted diet for 100 days in every measure from brain and from the periphery. All data were entered into GeneNetwork ( www.genenetwork.org ), a database that contains genotypic, phenotypic, and gene expression data (Rosen et al., Methods Mol Biol 401:287-303, 2007). Using this resource, we were able to ask the following four questions concerning possible candidate genes underlying our measures: (1) what is the range of response for each of the measures? (2) Does the pattern of variability show continuous (additive genetic) or discrete (Mendelian) distribution across strains? (3) Are there genetic markers that are associated with the variability in the measures? (4) Are there genes in near the markers that contain associated allelic differences, and whose expression is related to the variability in the measures? Other questions that we could address include: (5) what is the association among the measures between the sexes? (6) What is the association among the measures, e.g., is liver iron status under the diets related to brain iron? (7) What is the relationship between our measures and other phenotypic parameters-i.e., is there an association between our brain iron measures and neurochemical phenotypes extant in the database? And finally, (8) are there gene networks that underlie single or combined measures?
在本论文中，我们展示了系统遗传学 - 系统生物学方法在利用综合数据库研究铁调节方面的实用性。我们描述了在BXD重组近交小鼠品系家族中，正常铁饮食和铁限制饮食条件下大脑和外周铁调节的研究工作。通过多种测量方法，我们发现，在喂食100天铁限制饮食后，各品系在大脑和外周的各项测量指标上存在广泛差异。所有数据都录入了GeneNetwork（www.genenetwork.org），这是一个包含基因型、表型和基因表达数据的数据库（Rosen等人，《分子生物学方法》401:287 - 303，2007）。利用这一资源，我们能够就测量指标潜在的候选基因提出以下四个问题：（1）每个测量指标的反应范围是多少？（2）变异性模式在各品系中呈现连续（加性遗传）还是离散（孟德尔）分布？（3）是否存在与测量指标变异性相关的遗传标记？（4）标记附近是否存在包含相关等位基因差异且其表达与测量指标变异性相关的基因？我们还可以解决的其他问题包括：（5）不同性别测量指标之间的关联是什么？（6）测量指标之间的关联是什么，例如饮食条件下肝脏铁状态与脑铁之间是否相关？（7）我们的测量指标与其他表型参数之间的关系是什么，即我们的脑铁测量指标与数据库中现有的神经化学表型之间是否存在关联？最后，（8）是否存在构成单个或综合测量指标基础的基因网络？
