Sequence and Comparative Analysis of the Mouse 1-Megabase Region Orthologous to the Human 11p15 Imprinted Domain

  1. Patrick Onyango1,2,
  2. Webb Miller3,
  3. Jessica Lehoczky4,
  4. Cheuk T. Leung1,5,
  5. Bruce Birren4,
  6. Sarah Wheelan5,7,
  7. Ken Dewar4, and
  8. Andrew P. Feinberg1,2,5,6,8
  1. 1Institute of Genetic Medicine and 2Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 3Department of Computer Science and Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA; 4Whitehead Institute/MIT Center for Genome Research, Cambridge, Massachusetts 02141, USA; 5Department of Molecular Biology and Genetics and 6Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 7Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20894, USA

Abstract

A major barrier to conceptual advances in understanding the mechanisms and regulation of imprinting of a genomic region is our relatively poor understanding of the overall organization of genes and of the potentially important cis-acting regulatory sequences that lie in the nonexonic segments that make up 97% of the genome. Interspecies sequence comparison offers an effective approach to identify sequence from conserved functional elements. In this article we describe the successful use of this approach in comparing a ∼1-Mb imprinted genomic domain on mouse chromosome 7 to its orthologous region on human 11p15.5. Within the region, we identified 112 exons of known genes as well as a novel gene identified uniquely in the mouse region, termed Msuit, that was found to be imprinted. In addition to these coding elements, we identified 33 CpG islands and 49 orthologous nonexonic, nonisland sequences that met our criteria as being conserved, and making up 4.1% of the total sequence. These conserved noncoding sequence elements were generally clustered near imprinted genes and the majority were between Igf2 andH19 or within Kvlqt1. Finally, the location of CpG islands provided evidence that suggested a two-island rule for imprinted genes. This study provides the first global view of the architecture of an entire imprinted domain and provides candidate sequence elements for subsequent functional analyses.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF313042 to AF313150.]

Footnotes

  • 8 Corresponding author.

  • E-MAIL afeinberg{at}jhu.edu; FAX (410) 614-9819.

  • Article and publication are at www.genome.org/cgi/doi/10.1101/gr.161800.

    • Received August 24, 2000.
    • Accepted September 19, 2000.
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