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Comparing three species to identify mechanisms of imprinting
Edward R. Winstead


Scientists have identified long stretches of DNA sequence near two imprinted genes that are virtually identical in three species—humans, mice, and sheep. The common sequences may contain genomic elements involved in regulating imprinted genes. Unlike most genes, imprinted genes are expressed exclusively from one parental chromosome. How this happens is not known, and the researchers are trying to identify common sequences that may represent evolutionarily conserved mechanisms for regulating these genes.

Detail from schematic of Dlk1-Gtl2 regions in mouse, human, and sheep. View larger

Anne Ferguson-Smith, of the University of Cambridge, U.K., led the study. Her team sequenced the regions containing the Dlk1 and Gtl2 genes in mice and sheep, and compared these to the corresponding region of human chromosome 14. The result was a precise map of the evolutionarily conserved sequences in three mammals that will be a tool for investigating imprinting mechanisms.

The researchers then compared the Dlk1-Gtl2 locus to another imprinted region in the mouse—the Igf2-H19 locus. They found some similarities but also significant differences. "This indicates that the regulation of imprinted gene expression may be different in both regions," the researchers write in Genome Research. The researchers also discovered a third human imprinted gene in the region (which is also present in mice and sheep).

Nearly 50 imprinted genes in humans and mice have been identified. It is not known whether genomes contain elements that distinguish imprinted regions from the vast majority of genes that can be expressed from either parental chromosome.

But one way to address this question is to "to look for genomic features common to imprinted domains within species and to conduct comparative genomic analysis of imprinted regions between species," the researchers write. "This approach becomes more feasible as more imprinted domains are being cloned and characterized and more mammalian genomic sequence is being generated."

See related GNN article
»The Legacy of Solid Gold: Comparing human and sheep genomic sequences reveals six imprinted genes at the callipyge locus

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Paulsen, M. et al. Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region. Genome Res 11, 2085-2094 (December 2001).

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