Molecular genetics and structural genomics of the human protein kinase C gene module

BACKGROUND: Protein kinase C (PKC) has become a major focus among cell biologists interested in second-messenger signal transduction and much has been learned about differences in the cellular localization and function of its different isotypes. In this study we systematically address the genomic locations and gene structures of the human PKC gene module. RESULTS: We first carried out fine chromosomal mapping of all nine PKC genes by fluorescence in situ hybridization (FISH), using cosmid and BAC probes. The PKC genes are found to be dispersed throughout the genome, and in some positions distinct from those previously reported: PKCα is at 17q24, PKCβ at 16p12, PKCγ at 19q13.4, PKCδ at 3p21.2, PKCε at 2p21, PKCζ at 1p36.3, PKCη at 14q22-23, PKCθ at 10p15 and PKCι at 3q26. For PKCι, an additional FISH signal mapped on Xq21.3 revealed a pseudogene (derived by retrotransposition). PKCγ, ζ, and θ are found to map to the most distal positions on the chromosomes, potentially implicating telomere position effects in their expression. Using the complete human genome draft sequence and bioinformatics tools, we then carried out a systematic analysis of PKC gene structure, including determination of the occurrence of single-nucleotide polymorphisms corresponding to the PKC loci. CONCLUSION: This resource of genomic information now facilitates investigation of the PKC gene module in structural chromosomal abnormalities and human disease locus mapping studies.