Neurobiology of Disease (Oct 2001)
Gene Expression Profiling in Postmortem Rett Syndrome Brain: Differential Gene Expression and Patient Classification
- Carlo Colantuoni,
- Ok-Hee Jeon,
- Karim Hyder,
- Alex Chenchik,
- Anis H. Khimani,
- Vinodh Narayanan,
- Eric P. Hoffman,
- Walter E. Kaufmann,
- SakkuBai Naidu,
- Jonathan Pevsner
Affiliations
- Carlo Colantuoni
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Ok-Hee Jeon
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Karim Hyder
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Alex Chenchik
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Anis H. Khimani
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Vinodh Narayanan
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Eric P. Hoffman
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Walter E. Kaufmann
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- SakkuBai Naidu
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Jonathan Pevsner
- Department of Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Cognitive Neurology, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neurogenetics, Kennedy Krieger Institute, 707 North Broadway, Baltimore, Maryland, 21205; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205; CLONTECH Laboratories, Inc. Palo Alto, California, 94303; Perkin–Elmer NEN Life Science, Inc. Boston, Massachusetts, 02118; Department of Neurology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, 15213; Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.; Departments of Pathology and Psychiatry and Behavirol Science, Johns Hopkins Hospital, Baltimore, Maryland, 21205
- Journal volume & issue
-
Vol. 8,
no. 5
pp. 847 – 865
Abstract
The identification of mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MECP2) gene in Rett Syndrome (RTT) suggests that an inappropriate release of transcriptional silencing may give rise to RTT neuropathology. Despite this progress, the molecular basis of RTT neuropathogenesis remains unclear. Using multiple cDNA microarray technologies, subtractive hybridization, and conventional biochemistry, we generated comprehensive gene expression profiles of postmortem brain tissue from RTT patients and matched controls. Many glial transcripts involved in known neuropathological mechanisms were found to have increased expression in RTT brain, while decreases were observed in the expression of multiple neuron-specific mRNAs. Dramatic and consistent decreases in transcripts encoding presynaptic markers indicated a specific deficit in presynaptic development. Employing multiple clustering algorithms, it was possible to accurately segregate RTT from control brain tissue samples based solely on gene expression profile. Although previously achieved in cancers, our results constitute the first report of human disease classification using gene expression profiling in a complex tissue source such as brain.
