Genotypes and phenotypes

Within the framework of a pilot project on the analysis of the mouse proteo me, we investigated C57BL/6 mice (Mus musculus), a standard inbred strain o f the mouse, starting with the analysis of brain, liver and heart proteins. Tissue extraction and the separation of proteins were performed with techn iques offering a maximum of resolution. Proteins separated were analyzed by mass spectrometry. Gene-protein identification was performed by genetic an alyses using the European Collaborative Interspecific Backcross (EUCIB), es tablished from the two mouse species Mus musculus and Mus spretus. On the b asis of protein polymorphisms we mapped hundreds of genes on the mouse chro mosomes, allowing us new insight into the relationship between genotype and phenotype of proteins. In particular, the results showed that protein modi fications can be genetically determined, therefore representing their own c lass of protein phenotypes. In this context, results are discussed suggesti ng that phenotypes of single protein species may result from several genes. Accordingly, proteins are considered as polygenic traits. In contrast, one example demonstrates that proteins may also have pleiotropic effects: a si ngle gene mutation (a single altered protein) may affect several other prot eins. From these studies we conclude that gene-related functional proteomic s will show in the future that genetic diseases, defined today by clinical symptoms and considered as etiological entireties, can be subdivided into d ifferent diseases according to different affected genes.