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Molecular & Cellular Proteomics 6:1183-1187, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Investigation of Human Protein Variants and Their Frequency in the General Population^*,S

Dobrin Nedelkov^,,¶, David A. Phillips, Kemmons A. Tubbs and Randall W. Nelson

From the Intrinsic Bioprobes Inc. and Institute for Population Proteomics, Tempe, Arizona 85284

Genetic variations and posttranslational modifications give rise to structural diversity in fully expressed human proteins. Structural modifications can also be induced during the life cycle of a protein and can lead to impaired functioning and pathological conditions. Although a large number of protein modifications have been discovered thus far, their incidence among the general population has not been determined. Here we show that human proteins exhibit a wide range of modifications present at various frequencies in the general population. The screening of 1,000 individuals from four geographical regions in the United States for five plasma proteins revealed the existence of 27 protein modifications. Some variants, such as those resulting from oxidation and single amino acid terminal truncations, were observed in the majority of individuals, whereas point mutations and extensive sequence truncations were detected in only a few individuals. Gender correlations were observed for two protein modifications. The data obtained reveal the extent of structural diversity in the general populace and represent the first such catalogue of structural protein modifications. Systematic studies of this kind will help redefine the normal human proteome and reveal the effects of these modifications in pathological processes.

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