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Biomedical subjects

Matt Wayland

Publications and source records attributed to Matt Wayland.

2 recordsLinked to original sources

Application and optimization of microarray technologies for human postmortem brain studies.

A number of microarray investigations using human postmortem brain tissue have been published recently, exploring a multitude of human brain disorders with the aim of unraveling the underlying pathologies. Although the technology is still developing and lacks sufficient sensitivity with regard to detecting splice variants and low abundance transcripts, microarrays are becoming the prominent method for candidate gene screening in complex neuropsychiatric disorders. The use of postmortem tissue harbors a variety of potential pitfalls, however, which could result in unreliable or, at worst, meaningless results. During the course of our large-scale gene expression study on 150 human postmortem brain samples, using more than 200 Affymetrix GeneChips, we have identified several aspects within microarray experimental procedure that allows for the early identification of potentially unreliable samples. The general application of the guidelines and technical tips described here increase the efficiency, reliability, and amount of data generated by this powerful screening technology while reducing superfluous consumption of time and resources.

Brain Chemistry↗

Oligodendrocyte dysfunction in schizophrenia and bipolar disorder.

BACKGROUND: Results of array studies have suggested abnormalities in expression of lipid and myelin-related genes in schizophrenia. Here, we investigated oligodendrocyte-specific and myelination-associated gene expression in schizophrenia and bipolar affective disorder. METHODS: We used samples from the Stanley brain collection, consisting of 15 schizophrenia, 15 bipolar affective disorder, and 15 control brains. Indexing-based differential display PCR was done to screen for differences in gene expression in schizophrenia patients versus controls. Results were cross-validated with quantitative PCR, which was also used to investigate expression profiles of 16 other oligodendrocyte and myelin genes in schizophrenia and bipolar disorder. These genes were further investigated with an ongoing microarray analysis. FINDINGS: Results of differential display and quantitative PCR analysis showed a reduction of key oligodendrocyte-related and myelin-related genes in schizophrenia and bipolar patients; expression changes for both disorders showed a high degree of overlap. Microarray results of the same genes investigated by quantitative PCR correlated well overall. INTERPRETATION: Schizophrenia and bipolar brains showed downregulation of key oligodendrocyte and myelination genes, including transcription factors that regulate these genes, compared with control brains. These results lend support to and extend observations from other microarray investigations. Our study also showed similar expression changes to the schizophrenia group in bipolar brains, which thus lends support to the notion that the disorders share common causative and pathophysiological pathways.

Bipolar Disorder↗