Relevance and limitations of public databases for microarray design: a critical approach to gene predictions

Lambert, Jean‐Charles; Testa, E; Cognat, Valérie; Soula, Julie; Hot, David; Lemoine, Yves; Gaypay, G; Amouyel, Philippe

doi:10.1038/sj.tpj.6500184

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…We first annotated 5849 ORFs but 3101 were excluded following a systematic bioinformatic analysis. 13 We demonstrated that these 3101 ORFs-even if referenced in the international databases-did not have a biological relevance. We noticed that a non-negligible part of them were nonetheless present on a commercial pan-genomic microarray such as the U133A affymetrix one.…”

Section: Design Strategymentioning

confidence: 84%

“…[9][10][11][12] Consequently, we assumed that genes located in one of the loci of interest defined by previous genome scans and exhibiting a differential expression between patients and controls, could constitute potential candidate genes for AD. We applied our strategy to nine different chromosomal regions previously identified by genome scan studies 13 and selected a candidate gene expressed in cases but not in controls, the ornithine transcarbamylase (OTC) located on Xp21.1. We then tested the plausibility for this gene to be associated in AD physiopathology.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

et al. 2007

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To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer's disease (AD), we have developed a customized microarray containing all the ORFs (n = 2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT-PCR. We also detected mRNA expression of all the other urea cycle enzymes in AD brains. Immunochemistry experiments revealed that the OTC expression was strictly restricted to vascular endothelial cells in brain. Furthermore, OTC activity was 880% increased in the CSF of probable AD cases compared with controls. We analysed the association of the OTC À389 G/A and À241 A/G promoter polymorphisms with the risk of developing AD. We observed that rare haplotypes may be associated with the risk of AD through a possible modulation of the methylation of the OTC promoter. In conclusion, our results suggest the involvement of a new pathway in AD brains involving the urea cycle.

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Section: Design Strategymentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

et al. 2007

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“…We recently reported results obtained from a customised microarray containing all the genes (n=2,741) located within 9 chromosomal regions of interest (10). Assessment of the levels of gene expression in total RNA from frontal brain tissue of AD patients and controls showed that 106 genes were differentially expressed (11).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease

et al. 2009

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The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the e4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n = 945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE e4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE e4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the Ab 40 peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation.

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“…This work also demonstrates that it is essential to examine closely the orientation of sequences selected for inclusion on an oligonucleotide microarray to ensure the reliability of microarray data. This study adds to a growing number of issues encountered when relying on public databases for microarray gene selection (4,22). …”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, the probe density of current arrays is sufficiently large to make a manual selection of the genes impractical at best. To date, the technical aspects of probe design have been the focus of considerable discussion (2,3), however, the selection of the genes included on an array (4,5), a critical first step in a custom-designed microarray experiment, has received less attention.…”

Section: Introductionmentioning

confidence: 99%

In Silico Gene Selection Strategy for Custom Microarray Design

2004

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Microarray technology has become an important tool for studying large-scale gene expression for a diversity of biological applications. However, there are a number of experimental settings for which commercial arrays are either unsuitable or unavailable despite the existence of sequence information. With the increasing availability of custom array manufacturing services, it is now feasible to design high-density arrays for any organism having sequence data. However, there have been relatively few reports discussing gene selection, an important first step in array design. Here we propose an in silico strategy for custom microarray gene selection that is applicable to a wide range of organisms, based on utilizing public domain microarray information to interrogate existing sequence data and to identify a set of homologous genes in any organism of interest. We demonstrate the utility of this approach by applying it to the selection of candidate genes for a custom Xenopus laevis microarray. A significant finding of this study is that 3%-4% of Xenopus expressed sequence tags (ESTs) are in an orientation contrary to that indicated in the public database entry (http://mssaha.people.wm.edu/suppMSS.html).

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Relevance and limitations of public databases for microarray design: a critical approach to gene predictions

Cited by 7 publications

References 11 publications

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease

In Silico Gene Selection Strategy for Custom Microarray Design

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