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 approx90 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.