Mosaic Analysis with Double Markers Reveals Cell-Type-Specific Paternal Growth Dominance

SummaryGenomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (14375 K)

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Extension of mosaic analysis with double markers (MADM) to chromosomes 7 and 12 ► Probing genomic imprinting with single-cell resolution using chromosome disomy ► Discovery of chromosome- and cell-type specificity of imprinting effects ► Key roles of IGF2 signaling in paternal growth dominance in chr. 7 disomy