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Analysis of allelic differential expression in the human genome using allele-specific serial analysis of gene expression tags

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Abstract:

Recent reports have demonstrated that a significant proportion of human genes display allelic differential expression (ADE). ADE is associated with phenotypic variability and may contribute to complex genetic diseases. Here, we present a computational analysis of ADE using allele-specific serial analysis of gene expression (SAGE) tags representing 1295 human genes. We identified 472 genes for which unequal representation (>3-fold) of allele-specific SAGE tags was observed in at least one SAGE library, suggesting the occurrence of ADE. For 235 out of these 472 genes, the difference in the expression level between both allele-specific SAGE tags was statistically significant (p < 0.05). Eleven candidate genes were then subjected to experimental validation and ADE was confirmed for 8 out of these 11 genes. Our results suggest that at least 25% of the human genes display ADE and that allele-specific SAGE tags can be efficiently used for the identification of such genes.

De récents travaux ont démontré qu’une proportion significative des gènes humains présentent une expression allélique différentielle (ADE). L’ADE est associée à la variabilité phénotypique et pourrait contribuer à des maladies génétiques complexes. Dans ce travail, les auteurs présentent une analyse bioinformatique de l’ADE au moyen d’étiquettes SAGE allèle-spécifiques pour 1295 gènes humains. Les auteurs ont identifié 472 gènes pour lesquels une abondance différentielle (>3 fois) d’étiquettes SAGE allèle-spécifiques a été observée au sein d’au moins une banque d’étiquettes SAGE; ce qui suggère l’occurrence du phénomène d’ADE. Pour 235 de ces 472 gènes, la différence quant au niveau d’expression des deux étiquettes SAGE était statistiquement significative (p < 0,05). Onze gènes candidats ont ensuite été assujettis à une validation expérimentale et l’ADE a été confirmée pour 8 de ces 11 gènes. Ces résultats suggèrent qu’au moins 25 % des gènes humains présentent de l’ADE et que les étiquettes SAGE allèle-spécifiques constituent un outil efficace pour identifier de tels gènes.

Document Type: Research Article

Publication date: February 1, 2011

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  • From its inception in 1957, this international cytogenetics journal has catered to the research areas of the members of the Genetics Society of Canada; traditionally, these have included agriculture, entomology, genetics/cytogenetics, and evolutionary mechanisms. The contents of the journal have evolved as contributors developed new technologies and interests. A 20-member Editorial Board is composed of scientists from around the world. Reviews and commentary from respected experts are often featured.
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nrc/gen/2011/00000054/00000002/art00004
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