Saturday, November 25, 2006


Genomic Imprinting in Mammals: Emerging Themes and Established Theories

An open access/free review paper from PLoS Genetics:

Genomic Imprinting in Mammals: Emerging Themes and Established Theories

Andrew J. Wood, Rebecca J. Oakey

The epigenetic events that occur during the development of the mammalian embryo are essential for correct gene expression and cell-lineage determination. Imprinted genes are expressed from only one parental allele due to differential epigenetic marks that are established during gametogenesis. Several theories have been proposed to explain the role that genomic imprinting has played over the course of mammalian evolution, but at present it is not clear if a single hypothesis can fully account for the diversity of roles that imprinted genes play. In this review, we discuss efforts to define the extent of imprinting in the mouse genome, and suggest that different imprinted loci may have been wrought by distinct evolutionary forces. We focus on a group of small imprinted domains, which consist of paternally expressed genes embedded within introns of multiexonic transcripts, to discuss the evolution of imprinting at these loci.


The process of sexual reproduction dictates that mammals inherit two copies of every gene, one from the mother and one from the father. At most loci, both alleles are actively transcribed and functionally equivalent. Imprinted genes represent an exception to this rule, as the transcriptional activity of each allele is determined by the gender of the parental germ line to which it was most recently exposed. This parental legacy is initiated by epigenetic modifications such as DNA methylation, which is established in the parental germ line and maintained throughout somatic development in the offspring. Individual germ-line marks can control the allele-specific silencing or activation of multiple neighbouring genes, which leads in many instances to clusters of imprinted transcripts. Such loci represent an attractive paradigm for the study of epigenetic transcriptional regulation, as both the active and silent allele are present in the same cell nucleus, and therefore potentially exposed to the same trans-acting regulatory factors. Epigenetic abnormalities at imprinted loci have been observed in cloned mammals [1], and their disruption has been reported in a number of human developmental disorders and cancers [2].

Defining the Extent of Imprinting

Since the identification of the first autosomal imprinted genes in the early 1990s [3–5], much speculation has surrounded the question of how many exist. Attempts to count the exact number have been complicated by difficulties in defining exactly what constitutes a gene, as in several cases multiple functional components are derived from a single core of genetic information [6]. A recent census identified 96 imprinted functional components (54 maternally expressed, 42 paternally expressed) arising from 71 transcriptional units [7], and the relevant literature is summarised on the Harwell and University of Otago online databases [8,9].

A number of different approaches have been employed to define the extent of imprinting in the mouse genome. Mouse stocks carrying translocation chromosomes were used to define chromosomal regions that show parent-of-origin effects on phenotype when uniparentally inherited, and at least 13 distinct regions on eight chromosomes have been identified by this approach (C. V. Beechey, personal communication; [8]). The phenotypes range from early embryonic lethality to postnatal effects on growth and development, and are likely to result from the misexpression of imprinted genes situated within the uniparentally duplicated region [10]. The subsequent identification of imprinted genes on chromosomes without obvious uniparental effects [11-13] suggests that imprinting may be more widespread than initially thought, and not limited to genes that are vital for development. This conclusion is supported by the involvement of imprinted genes in behavioural traits in the mouse [14,15].

Continued at "Genomic Imprinting in Mammals: Emerging Themes and Established Theories"

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