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Comparative Study
. 2004 Jul;14(7):1268-74.
doi: 10.1101/gr.2090904.

Gene expression from the aneuploid chromosome in a trisomy mouse model of down syndrome

Robert Lyle  1 , Corinne Gehrig, Charlotte Neergaard-Henrichsen, Samuel Deutsch, Stylianos E Antonarakis
Affiliations
Comparative Study

Gene expression from the aneuploid chromosome in a trisomy mouse model of down syndrome

Robert Lyle et al. Genome Res. 2004 Jul.

Abstract

Trisomy 21 is the prototype of human aneuploidies. Since its discovery in 1959, the hypothesis has been that overexpression of the approximately 230 human chromosome 21 (Hsa21) genes result in the complex phenotype. However, the level of overexpression of Hsa21 genes in trisomic individuals is presently unknown. We have used Taqman real-time quantitative PCR to accurately measure expression of the mouse orthologs of Hsa21 in the partial trisomy mouse model Ts65Dn. The transcript levels of 78 protein-coding genes present in three copies in Ts65Dn and 21 control genes were compared between Ts65Dn and normal mouse littermates. The mean overexpression of the aneuploid genes is very close to the expected 1.5-fold in all six tissues studied. However, only approximately a third of the genes (37%) are expressed at the theoretical value of 1.5-fold. On average, 45% of the genes are expressed at significantly lower than 1.5-fold, and 9% are not significantly different from 1.0. Interestingly, 18% of the aneuploid genes were expressed at levels significantly greater than 1.5-fold. These data provide candidate genes that might be involved in the phenotypes of Down syndrome, and reveal a complex regulation of gene expression that is not only related to gene copy number.

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Figures

Figure 1
Figure 1
Example of Taqman real-time PCR amplification plot from P30 kidney of Ts65Dn and euploid mice. Two test genes (N6amt and C21orf18) and one normalization gene (Ppia) are shown. For each mouse genotype and gene there are five replicates. (Inset) The normalized relative expression of Ts65Dn to euploid (xΔe) and the standard error (SEM).
Figure 2
Figure 2
Normalized relative expression Ts/Eu (xΔe). The values are the expression of a gene for Ts65Dn relative to Eu for the tissues and stages shown. The colors represent expression relative to the theoretical values 1.5 and 1.0, based on 95% CI for the values.
Figure 3
Figure 3
Histogram of normalized relative expression Ts/Eu (xΔe). The values from Figure 2 are plotted into bins differing by 0.05. The dotted line indicates the position of the value 1.5.
Figure 4
Figure 4
Graphs of normalized relative expression Ts/Eu (xΔe). Points represent the values from Figure 2 and bars represent the 95% CI of these values. The x-axis has genes plotted along mouse Chromosome 16 for the test genes. The y-axis represents xΔe. The list and order of genes for each tissue is given in Figure 2.
See this image and copyright information in PMC

References

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WEB SITE REFERENCES

    1. www.ensembl.org; Ensembl homepage.
    1. www.jax.org; Jackson laboratories.

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