Gavaghan C L, Holmes E, Lenz E, Wilson I D, Nicholson J K
Biological Chemistry. Biomedical Sciences Division, Imperial College ofScience, University of London, UK.
FEBS Lett. 2000 Nov 10;484(3):169-74. doi: 10.1016/s0014-5793(00)02147-5.
As the human genome sequencing projects near completion, there is an active search for technologies that can provide insights into the genetic basis for physiological variation and interpreting gene expression in terms of phenotype at the whole organism level in order to understand the pathophysiology of disease. We present a novel metabonomic approach to the investigation of genetic influences on metabolic balance and metabolite excretion patterns in two phenotypically normal mouse models (C57BL10J and Alpk:ApfCD). Chemometric techniques were applied to optimise recovery of biochemical information from complex (1)H NMR urine spectra and to determine metabolic biomarker differences between the two strains. Differences were observed in tricarboxylic acid cycle intermediates and methylamine pathway activity. We suggest here a new 'metabotype' concept, which will be of value in relating quantitative physiological and biochemical data to both phenotypic and genetic variation in animals and man.
随着人类基因组测序项目接近完成，人们正在积极寻找能够深入了解生理变异的遗传基础，并在全生物体水平上根据表型解释基因表达，从而理解疾病病理生理学的技术。我们提出了一种新的代谢组学方法，用于研究两种表型正常的小鼠模型（C57BL10J和Alpk:ApfCD）中遗传因素对代谢平衡和代谢物排泄模式的影响。应用化学计量学技术优化从复杂的氢核磁共振尿液光谱中恢复生化信息，并确定两种品系之间的代谢生物标志物差异。观察到三羧酸循环中间体和甲胺途径活性存在差异。我们在此提出一个新的“代谢型”概念，这对于将定量生理和生化数据与动物和人类的表型及遗传变异联系起来具有重要价值。
