Neurogenetics

, Volume 7, Issue 2, pp 67–80

Gene expression analyses reveal molecular relationships among 20 regions of the human CNS

Authors

    • Department of Molecular Medicine, Neurocrine Biosciences, Incorporated
  • Peter Hevezi
    • Department of Molecular Medicine, Neurocrine Biosciences, Incorporated
  • Jerry Lee
    • Department of Molecular Medicine, Neurocrine Biosciences, Incorporated
  • Dorian Willhite
    • Department of Molecular Medicine, Neurocrine Biosciences, Incorporated
  • Sandra M. Lechner
    • Department of Neuroscience, Neurocrine Biosciences, Incorporated
  • Alan C. Foster
    • Department of Neuroscience, Neurocrine Biosciences, Incorporated
  • Albert Zlotnik
    • Department of Molecular Medicine, Neurocrine Biosciences, Incorporated
Original Article

DOI: 10.1007/s10048-006-0032-6

Cite this article as:
Roth, R.B., Hevezi, P., Lee, J. et al. Neurogenetics (2006) 7: 67. doi:10.1007/s10048-006-0032-6

Abstract

Transcriptional profiling was performed to survey the global expression patterns of 20 anatomically distinct sites of the human central nervous system (CNS). Forty-five non-CNS tissues were also profiled to allow for comparative analyses. Using principal component analysis and hierarchical clustering, we were able to show that the expression patterns of the 20 CNS sites profiled were significantly different from all non-CNS tissues and were also similar to one another, indicating an underlying common expression signature. By focusing our analyses on the 20 sites of the CNS, we were able to show that these 20 sites could be segregated into discrete groups with underlying similarities in anatomical structure and, in many cases, functional activity. These findings suggest that gene expression data can help define CNS function at the molecular level. We have identified subsets of genes with the following patterns of expression: (1) across the CNS, suggesting homeostatic/housekeeping function; (2) in subsets of functionally related sites of the CNS identified by our unsupervised learning analyses; and (3) in single sites within the CNS, indicating their participation in distinct site-specific functions. By performing network analyses on these gene sets, we identified many pathways that are upregulated in particular sites of the CNS, some of which were previously described in the literature, validating both our dataset and approach. In summary, we have generated a database of gene expression that can be used to gain valuable insight into the molecular characterization of functions carried out by different sites of the human CNS.

Keywords

Central nervous systemHumanTranscriptional profilingMicroarrayNetwork analysis

Abbreviations

ADORA2A

Adenosine A2a receptor

AMPH

Amphiphysin (Stiff–Man syndrome with breast cancer 128 kDa autoantigen)

CACNA1A

Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit

CACNA1B

Calcium channel, voltage-dependent, L type, alpha 1B subunit

CNS

Central nervous system

CRTAM

Class I MHC-restricted T cell-associated molecule

CTP

Cytosine triphosphate

DLG2

Discs, large homologue 2, chapsyn-110 (Drosophila)

DLG4

Discs, large homologue 4 (Drosophila)

DLGAP1

Discs, large (Drosophila) homologue-associated protein 1

DNM1

Dynamin 1

DRD2

Dopamine receptor D2EDNRB-endothelin receptor type B

EPS15

Epidermal growth factor receptor pathway substrate 15

FOSB

FBJ murine osteosarcoma viral oncogene homologue B

FYN

FYN oncogene related to SRC, FGR, and YES

GABRA6

Gamma-aminobutyric acid (GABA) A receptor, alpha 6

GPCR

G-protein coupled receptor

GRIK2

Glutamate receptor, ionotropic, kainate 2

GRIN1

Glutamate receptor, ionotropic, N-methyl D-aspartate 1

GRM3

Glutamate receptor, metabotropic 3

IPKB

Ingenuity Pathways Knowledge Base

IVT

In vitro transcription

MBP

Myelin basic protein

PCA

Principal component analysis

PCR

Polymerase chain reaction

PMCH

Pro-melanin-concentrating hormone

PMI

Postmortem interval

PNS

Peripheral nervous system

PTPN5

Protein tyrosine phosphatase, nonreceptor type 5

qPCR

Quantitative polymerase chain reaction

RAB3A

RAB3A, member RAS oncogene family

RMA

Robust multiarray analysis; robust multichip average

RNA

Ribonucleic acid

SFRP4

Secreted frizzled-related protein 4

SLC1A3

Solute carrier family 1 (glial high affinity glutamate transporter), member 3

SNAP25

Synaptosomal-associated protein, 25 kDa

SYT1

Synaptotagmin I

SYT3

Synaptotagmin III

SYT4

Synaptotagmin IV

TH

Tyrosine hydroxylase

TOI

Target of interest

UTP

Uridine triphosphate

VAMP2

Vesicle-associated membrane protein 2 (synaptobrevin 2)

Supplementary material

10048_2006_32_MOESM1_ESM.pdf (57 kb)
Table S1(PDF 58 kb)
10048_2006_32_MOESM2_ESM.pdf (63 kb)
Table S2(PDF 65 kb)
10048_2006_32_MOESM3_ESM.pdf (68 kb)
Table S3(PDF 70 kb)

Copyright information

© Springer-Verlag 2006