Identification of Parkinson's disease candidate genes

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The main pathological characteristic of the disease is the degeneration of dopaminergic neurons in Substantia Nigra pars compacta (SNpc). Familial linkage studies have linked thirteen human chromosomal loci, called PARK, which are to the disease and nine out of hundreds of genes located in these loci have been identified as PD genes. Identification of responsible gene(s) within large number of genes residing in these loci requires multiple approaches, including screening methods to narrow down the number of genes. Since several of the identified PD genes are expressed in the SNpc, expression within the neurons of this area could be a suitable criteria to limit the number of genes in PARK loci. In this work I have used the combination of findings from six transcriptome analysis studies, carried out in mice and rats, studying the gene expression profile of midbrain dopaminergic neurons, in addition to the PD linkage studies to identify further candidate genes for PD association studies. Merging the two sets of studies, I identified 20 genes in different PARK loci, 9 of which are located in orphan PD loci and one has been previously identified as a gene responsible for PD. This list expands the number of candidate genes, which can be further analyzed in genetic association studies and provide cues into the molecular and cellular basis for degeneration of mesencephalic dopaminergic neurons in SNpc, during the course of PD.