Genomic convergence to identify candidate genes for Parkinson's disease

SAGE analysis of the substantia nigra

Maher A. Noureddine, Yi Ju Li, Joelle M. van der Walt, Robert Walters, Rita M. Jewett, Hong Xu, Tianyuan Wang, Jeffrey W. Walter, Burton L. Scott, Christine Hulette, Don Schmechel, Judith E. Stenger, Fred Dietrich, Jeffery M Vance, Michael A. Hauser

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671-677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239-2242] to analyze substantia nigra tissue from three PD patients and two age-matched controls. We find 933 differentially expressed genes (P < 0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5-fold higher in PD patients versus controls, without an increase in the corresponding nuclear-encoded mitochondrial components, suggesting an increase in mtDNA genomes in PD or a disjunction with nuclear expression. The next step in the genomic convergence process will be to screen these 50 high-quality candidate genes for association with PD risk susceptibility and genetic effects on AAO.

Original languageEnglish
Pages (from-to)1299-1309
Number of pages11
JournalMovement Disorders
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Fingerprint

Substantia Nigra
Parkinson Disease
Genes
Mitochondrial DNA
Viverridae
Gene Expression
Disease Susceptibility
Age of Onset
Genome

Keywords

  • Genomic convergence
  • Linkage
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Noureddine, M. A., Li, Y. J., van der Walt, J. M., Walters, R., Jewett, R. M., Xu, H., ... Hauser, M. A. (2005). Genomic convergence to identify candidate genes for Parkinson's disease: SAGE analysis of the substantia nigra. Movement Disorders, 20(10), 1299-1309. https://doi.org/10.1002/mds.20573

Genomic convergence to identify candidate genes for Parkinson's disease : SAGE analysis of the substantia nigra. / Noureddine, Maher A.; Li, Yi Ju; van der Walt, Joelle M.; Walters, Robert; Jewett, Rita M.; Xu, Hong; Wang, Tianyuan; Walter, Jeffrey W.; Scott, Burton L.; Hulette, Christine; Schmechel, Don; Stenger, Judith E.; Dietrich, Fred; Vance, Jeffery M; Hauser, Michael A.

In: Movement Disorders, Vol. 20, No. 10, 01.10.2005, p. 1299-1309.

Research output: Contribution to journalArticle

Noureddine, MA, Li, YJ, van der Walt, JM, Walters, R, Jewett, RM, Xu, H, Wang, T, Walter, JW, Scott, BL, Hulette, C, Schmechel, D, Stenger, JE, Dietrich, F, Vance, JM & Hauser, MA 2005, 'Genomic convergence to identify candidate genes for Parkinson's disease: SAGE analysis of the substantia nigra', Movement Disorders, vol. 20, no. 10, pp. 1299-1309. https://doi.org/10.1002/mds.20573
Noureddine, Maher A. ; Li, Yi Ju ; van der Walt, Joelle M. ; Walters, Robert ; Jewett, Rita M. ; Xu, Hong ; Wang, Tianyuan ; Walter, Jeffrey W. ; Scott, Burton L. ; Hulette, Christine ; Schmechel, Don ; Stenger, Judith E. ; Dietrich, Fred ; Vance, Jeffery M ; Hauser, Michael A. / Genomic convergence to identify candidate genes for Parkinson's disease : SAGE analysis of the substantia nigra. In: Movement Disorders. 2005 ; Vol. 20, No. 10. pp. 1299-1309.
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