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

Michael A. Hauser, Yi Ju Li, Satoshi Takeuchi, Robert Walters, Maher Noureddine, Melinda Maready, Tiffany Darden, Christine Hulette, Eden Martin, Elizabeth Hauser, Hong Xu, Don Schmechel, Judith E. Stenger, Fred Dietrich, Jeffery Vance

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)671-677
Number of pages7
JournalHuman molecular genetics
Volume12
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Hauser, M. A., Li, Y. J., Takeuchi, S., Walters, R., Noureddine, M., Maready, M., Darden, T., Hulette, C., Martin, E., Hauser, E., Xu, H., Schmechel, D., Stenger, J. E., Dietrich, F., & Vance, J. (2003). Genomic convergence: Identifying candidate genes for Parkinson's disease by combining serial analysis of gene expression and genetic linkage. Human molecular genetics, 12(6), 671-677. https://doi.org/10.1093/hmg/ddg070