Parkinson's disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons.
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 identified 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.
Vahedi
Shahrooz
S
The Bahá'í Institute for Higher Education, Tehran, Iran.
Rajabian
Mehrnoosh
M
Misaghian
Arman
A
Grbec
Daniel
D
Simon
Horst H
HH
Alavian
Kambiz N
KN
D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics*; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology*
D009419:Nerve Tissue Proteins