Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2

Parental imprinting is a phenomenon in mammals whereby the maternal and paternal alleles of a gene are differentially expressed. Three murine genes have been shown to display this type of allele-specific expression. Two of them, insulin-like growth factor-2 (Igf-2) and H19, map to the distal end of mouse chromosome 7, but are imprinted in opposite directions. Pulsed-field gel electrophoresis and large-fragment DNA cloning were utilized to establish a physical map that includes H19 and Igf-2. Igf-2 lies approximately 90 kilobases of DNA 5' to H19, in the same transcriptional orientation. This physical proximity is conserved in humans, based on pulsed-field gel analysis. We conclude that H19 and Igf-2 constitute an imprinted domain.