Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes
- Rachel E. Ellsworth*,
- D. Curtis Jamison*,
- Jeffrey W. Touchman†,
- Stephanie L. Chissoe‡,
- Valerie V. Braden Maduro*,
- Gerard G. Bouffard†,
- Nicole L. Dietrich†,
- Stephen M. Beckstrom-Sternberg†,
- Leslie M. Iyer*,
- Lauren A. Weintraub*,
- Marc Cotton‡,
- Laura Courtney‡,
- Jennifer Edwards‡,
- Rachel Maupin‡,
- Philip Ozersky‡,
- Theresa Rohlfing‡,
- Patricia Wohldmann‡,
- Tracie Miner‡,
- Kimberley Kemp‡,
- Jason Kramer‡,
- Ian Korf‡,
- Kimberlie Pepin‡,
- Lucinda Antonacci-Fulton‡,
- Robert S. Fulton‡,
- Patrick Minx‡,
- LaDeana W. Hillier‡,
- Richard K. Wilson‡,
- Robert H. Waterston‡,
- Webb Miller§, and
- Eric D. Green*,†,¶
- *Genome Technology Branch and †National Institutes of Health Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; ‡Genome Sequencing Center, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110; and §Department of Computer Science and Engineering, Pennsylvania State University, University Park, PA 16802
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Communicated by Francis S. Collins, National Institutes of Health, Bethesda, MD (received for review September 17, 1999)
Abstract
The identification of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous advances in elucidating the function of the encoded protein and the physiological basis of cystic fibrosis. However, numerous areas of cystic fibrosis biology require additional investigation, some of which would be facilitated by information about the long-range sequence context of the CFTR gene. For example, the latter might provide clues about the sequence elements responsible for the temporal and spatial regulation of CFTR expression. We thus sought to establish the sequence of the chromosomal segments encompassing the human CFTR and mouse Cftr genes, with the hope of identifying conserved regions of biologic interest by sequence comparison. Bacterial clone-based physical maps of the relevant human and mouse genomic regions were constructed, and minimally overlapping sets of clones were selected and sequenced, eventually yielding ≈1.6 Mb and ≈358 kb of contiguous human and mouse sequence, respectively. These efforts have produced the complete sequence of the ≈189-kb and ≈152-kb segments containing the human CFTR and mouse Cftr genes, respectively, as well as significant amounts of flanking DNA. Analyses of the resulting data provide insights about the organization of the CFTR/Cftr genes and potential sequence elements regulating their expression. Furthermore, the generated sequence reveals the precise architecture of genes residing near CFTR/Cftr, including one known gene (WNT2/Wnt2) and two previously unknown genes that immediately flank CFTR/Cftr.
Footnotes
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↵ ¶ To whom reprint requests should be addressed at: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Building 49, Room 2A08, Bethesda, MD 20892. E-mail: egreen{at}nhgri.nih.gov.
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Data deposition: The sequences reported in the paper have been deposited in the GenBank database (accession nos. AC002542, AC003987, AC006326, AC002465, AC003045, AC000111, AC000061, AC004240, AC002431, AC003084, AC004536, AC006389, AC007874, AC004029, AC006926, AC002529, and AF162137).
- Abbreviations:
- CF,
- cystic fibrosis;
- BAC,
- bacterial artificial chromosome;
- PAC,
- P1-derived artificial chromosome;
- PIP,
- percent identity plot;
- STS,
- sequence-tagged site
- Copyright © 2000, The National Academy of Sciences
