Abstract
Genomic imprinting in mammals results in the expression of genes from only one parental allele. Imprinting occurs as a consequence of epigenetic marks set down either in the father's or the mother's germ line and affects a very specific category of mammalian gene. A greater understanding of this distinctive phenomenon can be gained from studies using large genomic clones, called bacterial artificial chromosomes (BACs). Here, we review the important applications of BACs to imprinting research, covering physical mapping studies and the use of BACs as transgenes in mice to study gene expression patterns, to identify imprinting centres, and to isolate the consequences of altered gene dosage. We also highlight the significant and unique advantages that rapid BAC engineering brings to genomic imprinting research.
Highlights
Genomic imprinting describes a unique class of genes that are expressed from only one parental allele as a consequence of epigenetic marks set down either in the father’s or the mother’s germ line [12] (Figure 1)
The first evidence that individual genes were imprinted came from studies on the mouse Insulin-like growth factor 2 (Igf2) gene [13]
In short succession, allele-specific gene expression was demonstrated for three genes in mice
Summary
Genomic imprinting describes a unique class of genes that are expressed from only one parental allele as a consequence of epigenetic marks set down either in the father’s or the mother’s germ line [12] (Figure 1). A transgene-based approach can provide information both on the mechanism of imprinting and the functional consequences of increased gene expression in a single model. In this respect, transgenes based on bacterial artificial chromosomes (BACs) have been of particular value. BACs can be used to study the developmental consequence of accurate but excess expression of single genes Thirdly, their amenability to modification techniques to insert or delete sequences and to alter sequences as discrete as a single point mutation [40,41,42,43,44] makes them a powerful tool for addressing both mechanistic and functional questions. Modified BACs can provide an important additional tool, alongside traditional targeting of endogenous loci in embryonic stem (ES) cells
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