Genomic and post-genomic analyses of human prion diseases

Prion diseases share common features of neurodegenerative disorders, infectious diseases and pathologies linked to misfolded proteins. Whether these aspects are independently and fortuitously present in prion diseases or are somewhat linked together remains unsettled, but the contribution of genomic, proteomic, metabolomic and spectroscopic techniques might give insights into this puzzle, and likely give hope for therapy to patients. Although the prion protein gene (PRNP) governs most of the clinical and pathological features of prion diseases and plays a pivotal role in determining host susceptibility, there are still many uncertainties and unknown risk factors that need to be clarified and identified. Several genes, other than PRNP, have recently been found to be associated with a risk of developing sporadic or variant Creutzfeldt-Jakob disease, but these novel data have been produced in a relatively small number of patients and controls and, therefore, need further confirmation. The same criticism applies to the identification of the over 20 new cerebrospinal fluid or plasma markers of disease. Some of these markers seem related to the massive brain damage that occurs, rather than being specific to prion infection. Nevertheless, genomic and post-genomic approaches have shown that these techniques are very powerful, and the best way to overcome the scantiness of samples would be to encourage strong collaboration between different centers of excellence in prion diseases. In this review, we describe the most recent and outstanding advances offered by genomics and post-genomics analyses in the field of human prion diseases.