BN phenome: detailed characterization of the cardiovascular, renal, and pulmonary systems of the sequenced rat
BN phenome: detailed characterization of the cardiovascular, renal, and pulmonary systems of the sequenced rat
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DOI：
10.1152/physiolgenomics.00288.2005
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发表时间：
2006-04-13
影响因子：
4.6
通讯作者：
Cowley, AW
中科院分区：
文献类型：
--
作者：
Kwitek, AE;Jacob, HJ;Cowley, AW
后基因组时代提供了将疾病表型与基因组序列联系起来的资源，即创建疾病“表型”。我们对测序的BN大鼠菌株（BN/NHsdMcwi）进行了详细的表征，为在测序基因组与其产生的生物学之间建立直接联系提供了第一次协同努力。为了使BN序列对研究人员具有广泛的价值，这些措施需要放在实验室大鼠光谱的背景下，以便它们的生理可以根据测序的BN作为基准。作为生成心血管和肺部疾病综合表型的重要一步，我们在测序的BN中测量了281个与心脏、肺和血液疾病相关的性状（http://www.pga.mcw.edu）。我们将这些数据与在多种遗传背景、两性和不同环境下测量的相同特征的数据进行了比较。我们表明，没有一个单一的菌株，近交或远交，可以被认为是生理控制菌株；什么是正常取决于被测量的性状和菌株的基因组背景。我们发现两性之间存在巨大差异，这也取决于基因组背景。通过结合所有研究菌株的值，我们为每个这些性状生成了一个“群体”平均值和正常范围的值，这些值比任何单个近交系或远交系的测量值更具遗传代表性。这些数据为与生物医学研究中研究的主要大鼠品系相比，测序后的BN大鼠的心血管、肺、血液和肾功能相关性状的生理比较提供了基线。
The postgenome era has provided resources to link disease phenotypes to the genomic sequence, i.e., creating a disease "phenome." Our detailed characterization of the sequenced BN rat strain (BN/NHsdMcwi) provides the first concerted effort in creating a direct link between a sequenced genome and its resulting biology. For the BN sequence to be of broad value to investigators, these measures need to be put into the context of the spectrum of the laboratory rats, so that their physiology can be benchmarked against the sequenced BN. As a major step in generating a comprehensive cardiovascular and pulmonary disease phenome, we measured 281 traits related to diseases of the heart, lung, and blood (http:// pga.mcw.edu) in the sequenced BN. We compared these data with those of the same traits measured across multiple genetic backgrounds, both genders, and differing environments. We show that no single strain, inbred or outbred, can be considered a physiological control strain; what is normal depends on what trait is being measured and the strains' genome backgrounds. We find vast differences between the genders, also dependent on genome background. By combining the values across all strains studied, we generated a "population" mean and normal range of values for each of these traits, which are more genetically representative than the measured values in any single inbred or outbred strain. These data provide a baseline for physiological comparison of traits related to cardiovascular, lung, blood, and renal function in the sequenced BN rats relative to the major strains of rats studied in biomedical research.