genome-wide analysis reveals a complex pattern of genomic imprinting in mice全基因组分析揭示了一个复杂的模式小鼠的基因组印记.pdfVIP

Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice 1 2 3 1 Jason B. Wolf *, James M. Cheverud , Charles Roseman , Reinmar Hager 1 Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom, 2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri, United States of America, 3 Department of Anthropology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America Abstract Parent-of-origin–dependent gene expression resulting from genomic imprinting plays an important role in modulating complex traits ranging from developmental processes to cognitive abilities and associated disorders. However, while gene- targeting techniques have allowed for the identification of imprinted loci, very little is known about the contribution of imprinting to quantitative variation in complex traits. Most studies, furthermore, assume a simple pattern of imprinting, resulting in either paternal or maternal gene expression; yet, more complex patterns of effects also exist. As a result, the distribution and number of different imprinting patterns across the genome remain largely unexplored. We address these unresolved issues using a genome-wide scan for imprinted quantitative trait loci (iQTL) affecting body weight and growth in mice using a novel three-generation design. We identified ten iQTL that display much more complex and diverse effect patterns than previously assumed, including four loci with effects similar to the callipyge mutation found in sheep. Three loci display a new phenotypic pattern that we refer to as bipolar dominance, where the two heterozygotes are different from each other while the two homozygotes