Human housekeeping genes, revisited.

Motivation: Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression.

Results: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62 839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index τ, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 50% of all expression patterns. We developed a binary classification, indicating for every gene the IB tissues in which it is overly expressed, and the 12 - IB tissues in which it shows low expression. The 85 dominant midrange patterns with IB = 2--11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny.

Availability: All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803.

Contact: doron.lancet@weizmann.ac.il

Supplementary information: Four tables available at the above site.

/pdf/genome-wide-midrange-transcription-profiles-reveal-1zh7dxkavq.pdf

Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification

Quantitative gene expression data are often normalized to the expression levels of control or so-called “housekeeping” genes. An inherent assumption in the use of housekeeping genes is that express...

GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues

Human housekeeping genes are compact

Usually the reference genes used in gene expression analysis have been chosen for their known or suspected housekeeping roles, however the variation observed in most of them hinders their effective use. The assessed lack of validated reference genes emphasizes the importance of a systematic study for their identification. For selecting candidate reference genes we have developed a simple in silico method based on the data publicly available in the wheat databases Unigene and TIGR.

/pdf/identification-and-validation-of-reference-genes-for-264cxr8ams.pdf

Identification and validation of reference genes for quantitative RT-PCR normalization in wheat

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

/pdf/a-compendium-of-gene-expression-in-normal-human-tissues-5b7b1ol4mf.pdf

A compendium of gene expression in normal human tissues.

Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-d-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABA(A) receptor subunits alpha3, beta1, beta2, and beta3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel K(V)2.1, hK(V)beta3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.

https://www.physiology.org/doi/pdf/10.1152/physiolgenomics.2001.5.1.21

Differential gene expression profiling in human brain tumors.

At the forefront of the revolution in human genomics is DNA microarray technology, which evaluates expression levels or genotypes of thousands of genes simultaneously, by means of miniaturization and parallel processing. Furthermore, advances in bioinformatics will result in the creation of large databases, which will require complex software programming for structural analysis. Over the next decade, DNA microarrays, combined with sophisticated informatics and genomic databases, will provide molecular fingerprints of disease processes and prognoses. This review provides an update on DNA microarray technology and its application to renal diseases.

Robert L. Hong

Papers

A compendium of gene expression in normal human tissues.

Differential gene expression profiling in human brain tumors.

Prospective use of DNA microarrays for evaluating renal function and disease.

tumorsgene expression profiling in human brain