The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Clin Chem. 2010 Feb;56(2):202-11. doi: 10.1373/clinchem.2009.134858. Epub 2009 Nov 19.
Diversity in human proteins often gives rise to pluralities of structurally similar but functionally distinct proteins. Such microheterogeneity generally escapes proteomics discovery technologies, as well as conventional immunometric assays. As an intermediate between these 2 technological approaches, targeted, full-length characterization of proteins using mass spectrometry is a suitable means of defining microheterogeneity evident in human populations.
We describe and explore the implications of microheterogeneity using the exemplar of human vitamin D binding protein (Gc-Globulin) as observed in cohorts of 400 individuals. Our investigations yielded: (a) population frequency data comparable to genotyping; (b) population frequency data for protein variants, with and without genotype linkage; (c) reference values for the different protein variants per cohort and genotype; and (d) associations between variant, frequency, relative abundance, and diseases.
With the exception of the genotype frequency, such population data are unique and illustrate a need to more fully understand the exact full-length qualitative and quantitative idiosyncrasies of individual proteins in relation to health and disease as part of the standardized biomarker development and clinical proteomic investigation of human proteins.
人类蛋白质的多样性通常会产生多种结构相似但功能不同的蛋白质。这种微观异质性通常会逃避蛋白质组学发现技术以及传统的免疫计量测定法。作为这两种技术方法之间的中间产物，使用质谱法对全长蛋白质进行靶向、全面的特征描述是定义人群中明显存在的微观异质性的合适方法。
我们以人类维生素 D 结合蛋白（Gc-球蛋白）为例，描述并探讨了微观异质性的含义，该蛋白在 400 个人的队列中得到了观察。我们的研究结果包括：（a）与基因分型相当的人群频率数据；（b）具有和不具有基因型连锁的蛋白质变异体的人群频率数据；（c）每个队列和基因型的不同蛋白质变异体的参考值；以及（d）变异体、频率、相对丰度与疾病之间的关联。
除了基因型频率之外，此类人群数据是独特的，这表明需要更全面地了解个体蛋白质在健康和疾病方面的全长定性和定量特征，这是标准化生物标志物开发和人类蛋白质临床蛋白质组学研究的一部分。
