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Genetics Influences Allelic Expression Patterns

« Back to Volume 24, Issue 2, November 2008 - Table of Contents

Maternal and paternal alleles of autosomal genes were historically assumed to be expressed at the same levels. However, recent observations suggest that their expression may differ, ie, differential allelic expression (DAE), and that this difference may contribute to variability of clinical phenotypes in dominantly inherited disorders. To determine if there is a genetic component to DAE, Cheung et al examined patterns of allele expression in monozygotic twins.

The authors studied lymphoblastoid B cells from 21 monozygotic twins and 10 unrelated individuals. They took advantage of single nucleotide polymorphisms (SNPs) that map to exons so that they could be detected in mRNA and identified 285 instances in which “A” and “B” alleles could be distinguished in the respective mRNA transcripts. To determine the extent of differential expression of these alleles regardless of twinning, they first examined DAE in one member of each twin pair and the unrelated individuals using deviation from equal expression of the 2 alleles as a measure of DAE. Deviation was considered nominally statistically significant for half of the allele pairs, and 17% displayed an expression difference of 2-fold or more for one allele over the other.

Next they searched for DAE in the monozygotic twins utilizing 211 SNPs that were found to be heterozygous in 5 or more twin pairs and did an analysis of variance to determine the significance of twin resemblance. The results revealed much greater similarity between twins than predicted by chance. In a few instances in which more than one informative SNPs mapped to the same gene, the results were concordant. Twin resemblance for DAE was detected not only for genes whose alleles deviated substantially from equal expression, but also for genes whose alleles are expressed at relatively similar levels.
The authors drew 2 conclusions from their results. First, at least 50% of genes expressed in lymphoblastoid B cells show some degree of DAE. The difference is greater than 2-fold for some genes. Second, much of the observed DAE seems to be under genetic control.

Cheung VG, Bruzel A, Burdick JT, Morley M, Devlin JL, Spielman RS. Monozyogotic twins reveal germline contribution to allelic expression differences. Am J Hum Genet. 2008. 82:1357-60.

Editor’s Comment

This investigation provides another explanation for why monozyogotic twins are so similar. A paper was recently reviewed in GGH^1,2 suggesting that patterns of epigenetic modification diverge in monozygotic twins as they age. Since epigenetic modification influences expression of genes, one wonders if DAE varies with age or correlates at all with such modifications. Similarly, it would be interesting to know the extent to which DAE occurs in cell types other than lymphoblastoid B cells.

William A. Horton, MD

References - (linked to )

« Back to Volume 24, Issue 2, November 2008 - Table of Contents

Last Updated: 2/2/2011