TAILIEUCHUNG - Parkinson’s disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons

Parkinson’s disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson’s disease. Identification of gene(s), as part of the etiology of Parkinson’s disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria. Since several of the indentified Parkinson’s disease genes are expressed in substantia nigra pars compact of the midbrain,. | Vahedi et al. Journal of Biomedical Science 2010 17 66 http content 17 1 66 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Parkinson s disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons 1 1 12 2 Shahrooz Vahedi Mehrnoosh Rajabian Arman Misaghian Daniel Grbec Horst H Simon Kambiz N Alavian Abstract Background Parkinson s disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson s disease. Identification of gene s as part of the etiology of Parkinson s disease within the large number of genes residing in these loci can be achieved through several approaches including screening methods and considering appropriate criteria. Since several of the indentified Parkinson s disease genes are expressed in substantia nigra pars compact of the midbrain expression within the neurons of this area could be a suitable criterion to limit the number of candidates and identify PD genes. Methods In this work we have used the combination of findings from six rodent transcriptome analysis studies on the gene expression profile of midbrain dopaminergic neurons and the PARK loci in OMIM Online Mendelian Inheritance in Man database to identify new candidate genes for Parkinson s disease. Results Merging the two datasets we identified 20 genes within PARK loci 7 of which are located in an orphan Parkinson s disease locus and one which had been identified as a disease gene. In addition to identifying a set of candidates for further genetic association studies these results show that the criteria of expression in midbrain dopaminergic neurons may be used to narrow down the number of genes in PARK loci for such studies. Background Selective

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