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Human Molecular Genetics, 2003, Vol. 12, No. 6 671-677
© 2003 Oxford University Press

Genomic convergence: identifying candidate genes for Parkinson's disease by combining serial analysis of gene expression and genetic linkage

Michael A. Hauser1,*, Yi-Ju Li1, Satoshi Takeuchi1, Robert Walters1, Maher Noureddine1, Melinda Maready1, Tiffany Darden1, Christine Hulette3, Eden Martin1, Elizabeth Hauser1, Hong Xu1, Don Schmechel4, Judith E. Stenger1, Fred Dietrich2 and Jeffery Vance1

1Center for Human Genetics, 2Department of Molecular Genetics and Microbiology, 3Department of Pathology, and 4Department of Medicine, Duke University, Durham, NC 27710, USA

Received November 25, 2002; Accepted January 22, 2003

We present a multifactorial, multistep approach called genomic convergence that combines gene expression with genomic linkage analysis to identify and prioritize candidate susceptibility genes for Parkinson's disease (PD). To initiate this process, we used serial analysis of gene expression (SAGE) to identify genes expressed in two normal substantia nigras (SN) and adjacent midbrain tissue. This identified over 3700 transcripts, including the three most abundant SAGE tags, which did not correspond to any known genes or ESTs. We developed high-throughput bioinformatics methods to map the genes corresponding to these tags and identified 402 SN genes that lay within five large genomic linkage regions, previously identified in 174 multiplex PD families. These genes represent excellent candidates for PD susceptibility alleles and further genomic convergence and analyses.

* To whom correspondence should be addressed at: Center for Human Genetics, Duke University Medical Center, DUMC, Box 2903, Durham, NC 27710-2903, USA. Tel: +1 9196843508; Fax: +1 9196840919; Email: mike.hauser{at}duke.edu


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