Biomedical subjects

Michael L Mimmack

Publications and source records attributed to Michael L Mimmack.

3 recordsLinked to original sources

PubMed2004

Quantitative polymerase chain reaction: validation of microarray results from postmortem brain studies.

Quantitative polymerase chain reaction (Q-PCR) is now considered the "technique of choice" for validating gene expression changes identified with ribonucleic acid-based expression profiling technologies (especially micro- and macroarray techniques). The identification of altered gene expression profiles with microarrays is best viewed as the first step in the determination of potential disease-associated genes; however, the false-positive rate can be high, particularly with small sample sets and in view of the typically small differences observed in brain expression studies. Quantitative PCR is a rapid and highly sensitive technique for accurate quantification of microarray results; however, careful consideration of experimental design, quality of primer/probe design, internal standards, and normalization procedures are pivotal, particularly when the work involves postmortem tissue.

Apolipoprotein L1↗

PubMed2003

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↗

PubMed2002

Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22.

We screened a custom-made candidate gene cDNA array comprising 300 genes. Genes chosen have either been implicated in schizophrenia, make conceptual sense in the light of the current understanding of the disease, or are located on high-susceptibility chromosome locations. The array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control brains revealed robust up-regulation of apolipoprotein L1 (apo L1) by 2.6-fold. The finding was cross-validated in a blinded quantitative PCR study using prefrontal cortex tissue from the Stanley Foundation brain collection, Bethesda, MD. This collection consists of 15 schizophrenia, 15 bipolar disorder, 15 major depression, and 15 control individuals, all 60 brains being well-matched on conventional parameters, with antipsychotic drug exposure in the schizophrenia and bipolar disorder groups. Significant up-regulation of apo L1 gene expression in schizophrenia was confirmed. Using quantitative PCR, expression profiles of other members of the apo L family (apo L2-L6) were investigated, showing that apo L2 and L4 were highly significantly up-regulated in schizophrenia. Results were then confirmed in an independent set of 20 schizophrenia and 20 control brains from Japan and New Zealand. Apo L proteins belong to the group of high density lipoproteins, with all six apo L genes located in close proximity to each other on chromosome 22q12, a confirmed high-susceptibility locus for schizophrenia and close to the region associated with velocardiofacial syndrome that includes symptoms of schizophrenia.

Apolipoprotein L1↗