recent assembly of an imprinted domain from non-imprinted components最近印领域从non-imprinted组件的装配.pdfVIP

Recent Assembly of an Imprinted Domain from Non-Imprinted Components 1[ 1[ 2 3 3 3 Robert W. Rapkins , Tim Hore , Megan Smithwick , Eleanor Ager , Andrew J. Pask , Marilyn B. Renfree , 4 4 5 1 1* Matthias Kohn , Horst Hameister , Robert D. Nicholls , Janine E. Deakin , Jennifer A. Marshall Graves 1 Australian Research Council Center for Kangaroo Genomics and Research School of Biological Sciences, Australian National University, Canberra, Australia, 2 Department of Genetics, La Trobe University, Melbourne, Australia, 3 Department of Zoology, University of Melbourne, Melbourne, Australia, 4 Department of Medical Genetics, University of Ulm, Ulm, Germany, 5 Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Genomic imprinting, representing parent-specific expression of alleles at a locus, raises many questions about how— and especially why—epigenetic silencing of mammalian genes evolved. We present the first in-depth study of how a human imprinted domain evolved, analyzing a domain containing several imprinted genes that are involved in human disease. Using comparisons of orthologous genes in humans, marsupials, and the platypus, we discovered that the Prader-Willi/Angelman syndrome region on human Chromosome 15q was assembled only recently (105–180 million years ago). This imprinted domain arose after a region bearing UBE3A (Angelman syndrome) fused with an unlinked region bearing SNRPN (Prader-Willi syndrome), which had duplicated from the non-imprinted SNRPB/B 9. This region independently acquired several retroposed gene copies and arrays of small nucleolar RNAs from different parts of the genome. In their or