DNA chips: An array of possibilities

Marshall, A.C.; Hodgson, John

doi:10.1038/nbt0198-27

Cited by 355 publications

(174 citation statements)

References 3 publications

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“…The development of high-density synthetic oligonucleotide microarrays has enabled the relative expression of a broad range of genes to be determined in small samples of human tissue. 13 In addition to providing insight into the changes in gene expression that are associated with NASH, the identification of differential hepatic expression of genes that mediate mitochondrial function and/or insulin sensitivity would raise the possibility of a genetic predisposition to NAFLD and NASH.…”

Section: T He Term Nonalcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis

et al. 2003

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Although the molecular basis for the pathophysiology of nonalcoholic steatohepatitis (NASH) is poorly understood, insulin resistance and mitochondrial dysfunction are physiologic hallmarks of this condition. We sought evidence of a transcriptional or pretranscriptional basis for insulin resistance and mitochondrial dysfunction through measurement of hepatic gene expression (messenger RNA [mRNA]) using high-density synthetic oligonucleotide microarray analysis (Hu6800 GeneChip, Affymetrix, CA). Global hepatic gene expression was determined in snap-frozen liver biopsy specimens from 4 groups: (1) patients with cirrhotic-stage NASH (n ‫؍‬ 6), (2) patients with cirrhosis caused by hepatitis C virus (HCV) (n ‫؍‬ 6), (3) patients with cirrhosis secondary to primary biliary cirrhosis (PBC) (n ‫؍‬ 6), and (4) healthy controls (n ‫؍‬ 6). Genes were considered to be expressed differentially in NASH only if there was a greater than 2-fold difference in abundance of mRNA when compared with each of the control groups. Sixteen genes were uniquely differentially expressed (4 overexpressed and 12 underexpressed) in patients with cirrhotic-stage NASH. Genes that were significantly underexpressed included genes important for maintaining mitochondrial function (copper/zinc superoxide dismutase, aldehyde oxidase, and catalase). Glucose 6-phospatase, alcohol dehydrogenase, elongation factor-TU, methylglutaryl coenzyme A (CoA), acyl CoA synthetase, oxoacyl CoA thiolase, and ubiquitin also were underexpressed in NASH. Genes that were overexpressed in NASH included complement component C3 and hepatocyte-derived fibrinogen-related protein, potentially contributing to impaired insulin sensitivity. In conclusion, these studies provide evidence for a transcriptional or pretranscriptional basis for impaired mitochondrial function (attenuated capacity for the dismutation of reactive oxygen species) and diminished insulin sensitivity (increased acute phase reactants) in patients with histologically progressive NASH. Further studies are required to determine the mechanism and the physiologic significance of these findings. (HEPATOLOGY 2003;38:244-251.)

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Section: T He Term Nonalcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis

et al. 2003

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“…Updates will clearly be needed in the future, and other recent reviews offer alternative opinions. 52,[140][141][142][143] The technology option which is best will be driven by different criteria for different users. The relative importance of upfront and ongoing operational costs and how adaptable and generalizable a technology is will depend on whether one is in an academic biomedical research center, a clinical molecular diagnostics laboratory or the pharmaceutical industry, among other venues.…”

Section: Discussionmentioning

confidence: 99%

Parallel molecular genetic analysis

et al. 1998

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We describe recent progress in parallel molecular genetic analyses using DNA microarrays, gel-based systems, and capillary electrophoresis and utilization of these approaches in a variety of molecular biology assays. These applications include use of polymorphic markers for mapping of genes and disease-associated loci and carrier detection for genetic diseases. Application of these technologies in molecular diagnostics as well as fluorescent technologies in DNA analysis using immobilized oligonucleotide arrays on silicon or glass microchips are discussed. The array-based assays include sequencing by hybridization, cDNA expression profiling, comparative genome hybridization and genetic linkage analysis. Developments in non microarraybased, parallel analyses of mutations and gene expression profiles are reviewed. The promise of and recent progress in capillary array electrophoresis for parallel DNA sequence analysis and genotyping is summarized. Finally, a framework for decision making in selecting available technology options for specific molecular genetic analyses is presented.

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“…a wild-type strain's expressed genes) by hybridizing the labeled cDNA to the whole cell genome displayed on the DNA microarray. This methodology is extremely useful for studying pleiotropic regulatory effects, for example, those involved in stress response, in complex regulatory cascades and in resistance mechanisms against antibiotics, antimicrobial peptides, phages and/or industrial stress conditions [6,7,8 • , [14][15][16][17][18].…”

Section: Differential Gene Expressionmentioning

confidence: 99%