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Technology Insight: querying the genome with microarrays—progress and hope for neurological disease

Nature Clinical Practice Neurology volume 2, pages 147–158 (2006)Cite this article

Abstract

The ability to perform large-scale analysis of the genome at the level of gene sequence, gene copy number and messenger RNA transcript expression characterizes the post-genomic era. In the past decade, the microarray-based approach has emerged as one of the major tools in this area of genome biology, contributing to advances in the understanding of Mendelian and complex neurological disorders. Despite technical issues regarding design, data analysis and validation that have to be addressed in the planning and interpretation of a microarray study, microarray-based approaches for studying transcript expression, single-nucleotide-polymorphism genotyping and gene resequencing are becoming more widely adopted. Genomic microarrays are providing an unprecedented opportunity to dissect the genetic risk for complex neurological disorders. Numerous clinical and preclinical applications are likely to dominate the ambitious microarray agenda within the next decade.

Key Points

  • Microarrays were introduced to the scientific community in the mid-1990s as a method for screening a very large number of transcripts simultaneously

  • In the nervous system, microarrays provide opportunities to study the genetic basis and pathogenesis of disorders that show Mendelian or complex patterns of inheritance, and to provide more accurate diagnosis and more effective therapy

  • Expression profiling in models of Huntington's disease has contributed to the characterization of pathogenic gene expression changes, and indicated that some steps of Huntington's disease pathogenesis are shared among other polyglutamine disorders

  • Complex neurological disorders that are being studied using microarrays include Alzheimer's disease, Parkinson's disease, autism, amyotrophic lateral sclerosis and multiple sclerosis

  • Microarray experiments require a large analytical and follow-up component, and therefore need to be approached with considerable commitment of time, expertise and resources

  • Neuro-oncology provides a model for the use of microarrays in characterizing patients by prognosis and treatment response

  • Genomic microarrays are now being developed to study disease-associated changes in DNA sequences

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Figure 1: Microarray-based applications and neurological disorders.
Figure 2: Patient classification in neuro-oncology.
Figure 3: Gene resequencing.

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  1. G Coppola is an assistant researcher and DH Geschwind is a professor of neurology

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  1. psychiatry and genetics and Director of the Neurogenetics Program and the Center for Autism Research, at the University of California Los Angeles, CA, USA

    Giovanni Coppola & Daniel H Geschwind

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Correspondence to Daniel H Geschwind.

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Coppola, G., Geschwind, D. Technology Insight: querying the genome with microarrays—progress and hope for neurological disease. Nat Rev Neurol 2, 147–158 (2006). https://doi.org/10.1038/ncpneuro0133

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