Comparative analyses of multi-species sequences from targeted genomic regions

Thomas, J. W.; Touchman, J. W.; Blakesley, R. W.; Bouffard, G. G.; Beckstrom-Sternberg, S. M.; Margulies, E. H.; Blanchette, M.; Siepel, A. C.; Thomas, P. J.; McDowell, J. C.; Maskeri, B.; Hansen, N. F.; Schwartz, M. S.; Weber, R. J.; Kent, W. J.; Karolchik, D.; Bruen, T. C.; Bevan, R.; Cutler, D. J.; Schwartz, S.; Elnitski, L.; Idol, J. R.; Prasad, A. B.; Lee-Lin, S.-Q.; Maduro, V. V. B.; Summers, T. J.; Portnoy, M. E.; Dietrich, N. L.; Akhter, N.; Ayele, K.; Benjamin, B.; Cariaga, K.; Brinkley, C. P.; Brooks, S. Y.; Granite, S.; Guan, X.; Gupta, J.; Haghighi, P.; Ho, S.-L.; Huang, M. C.; Karlins, E.; Laric, P. L.; Legaspi, R.; Lim, M. J.; Maduro, Q. L.; Masiello, C. A.; Mastrian, S. D.; McCloskey, J. C.; Pearson, R.; Stantripop, S.; Tiongson, E. E.; Tran, J. T.; Tsurgeon, C.; Vogt, J. L.; Walker, M. A.; Wetherby, K. D.; Wiggins, L. S.; Young, A. C.; Zhang, L.-H.; Osoegawa, K.; Zhu, B.; Zhao, B.; Shu, C. L.; De Jong, P. J.; Lawrence, C. E.; Smit, A. F.; Chakravarti, A.; Haussler, D.; Green, P.; Miller, W.; Green, E. D.

Comparative analyses of multi-species sequences from targeted genomic regions

J. W. Thomas, J. W. Touchman, R. W. Blakesley, G. G. Bouffard, S. M. Beckstrom-Sternberg, E. H. Margulies, M. Blanchette, A. C. Siepel, P. J. Thomas, J. C. McDowell, B. Maskeri, N. F. Hansen, M. S. Schwartz, R. J. Weber, W. J. Kent, D. Karolchik, T. C. Bruen, R. Bevan, D. J. Cutler, S. Schwartz, L. Elnitski, J. R. Idol, A. B. Prasad, S.-Q. Lee-Lin, V. V. B. Maduro, T. J. Summers, M. E. Portnoy, N. L. Dietrich, N. Akhter, K. Ayele, B. Benjamin, K. Cariaga, C. P. Brinkley, S. Y. Brooks, S. Granite, X. Guan, J. Gupta, P. Haghighi, S.-L. Ho, M. C. Huang, E. Karlins, P. L. Laric, R. Legaspi, M. J. Lim, Q. L. Maduro, C. A. Masiello, S. D. Mastrian, J. C. McCloskey, R. Pearson, S. Stantripop, E. E. Tiongson, J. T. Tran, C. Tsurgeon, J. L. Vogt, M. A. Walker, K. D. Wetherby, L. S. Wiggins, A. C. Young, L.-H. Zhang, K. Osoegawa, B. Zhu, B. Zhao, C. L. Shu, P. J. De Jong, C. E. Lawrence, A. F. Smit, A. Chakravarti, D. Haussler, P. Green, W. Miller and E. D. Green ()
Additional contact information
J. W. Thomas: National Human Genome Research Institute
J. W. Touchman: National Human Genome Research Institute
R. W. Blakesley: National Human Genome Research Institute
G. G. Bouffard: National Human Genome Research Institute
S. M. Beckstrom-Sternberg: National Human Genome Research Institute
E. H. Margulies: National Human Genome Research Institute
M. Blanchette: University of California
A. C. Siepel: University of California
P. J. Thomas: National Institutes of Health
J. C. McDowell: National Institutes of Health
B. Maskeri: National Institutes of Health
N. F. Hansen: National Institutes of Health
M. S. Schwartz: University of California
R. J. Weber: University of California
W. J. Kent: University of California
D. Karolchik: University of California
T. C. Bruen: University of California
R. Bevan: University of California
D. J. Cutler: Johns Hopkins University School of Medicine
S. Schwartz: The Pennsylvania State University
L. Elnitski: The Pennsylvania State University
J. R. Idol: National Human Genome Research Institute
A. B. Prasad: National Human Genome Research Institute
S.-Q. Lee-Lin: National Human Genome Research Institute
V. V. B. Maduro: National Human Genome Research Institute
T. J. Summers: National Human Genome Research Institute
M. E. Portnoy: National Human Genome Research Institute
N. L. Dietrich: National Institutes of Health
N. Akhter: National Institutes of Health
K. Ayele: National Institutes of Health
B. Benjamin: National Institutes of Health
K. Cariaga: National Institutes of Health
C. P. Brinkley: National Institutes of Health
S. Y. Brooks: National Institutes of Health
S. Granite: National Institutes of Health
X. Guan: National Institutes of Health
J. Gupta: National Institutes of Health
P. Haghighi: National Institutes of Health
S.-L. Ho: National Institutes of Health
M. C. Huang: National Institutes of Health
E. Karlins: National Institutes of Health
P. L. Laric: National Institutes of Health
R. Legaspi: National Institutes of Health
M. J. Lim: National Institutes of Health
Q. L. Maduro: National Institutes of Health
C. A. Masiello: National Institutes of Health
S. D. Mastrian: National Institutes of Health
J. C. McCloskey: National Institutes of Health
R. Pearson: National Institutes of Health
S. Stantripop: National Institutes of Health
E. E. Tiongson: National Institutes of Health
J. T. Tran: National Institutes of Health
C. Tsurgeon: National Institutes of Health
J. L. Vogt: National Institutes of Health
M. A. Walker: National Institutes of Health
K. D. Wetherby: National Institutes of Health
L. S. Wiggins: National Institutes of Health
A. C. Young: National Institutes of Health
L.-H. Zhang: National Institutes of Health
K. Osoegawa: Children's Hospital Oakland Research Institute
B. Zhu: Children's Hospital Oakland Research Institute
B. Zhao: Children's Hospital Oakland Research Institute
C. L. Shu: Children's Hospital Oakland Research Institute
P. J. De Jong: Children's Hospital Oakland Research Institute
C. E. Lawrence: New York State Department of Health
A. F. Smit: The Institute for Systems Biology
A. Chakravarti: Johns Hopkins University School of Medicine
D. Haussler: University of California
P. Green: University of Washington
W. Miller: The Pennsylvania State University
E. D. Green: National Human Genome Research Institute

Nature, 2003, vol. 424, issue 6950, 788-793

Abstract: Abstract The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding1,2,3,4,5,6 and conserved non-coding4,6,7 regions, including regulatory elements8,9,10, and provide insight into the forces that have rendered modern-day genomes6. As a complement to whole-genome sequencing efforts3,5,6, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Date: 2003
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DOI: 10.1038/nature01858

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