Comparative analyses of multi-species sequences from targeted genomic regions

J. W. Thomas, J. W. Touchman, R. W. Blakesley, G. G. Bouffard, Stephen 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 & 51 others 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, E. D. Green

Research output: Contribution to journalArticle

482 Citations (Scopus)

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 coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, 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.

Original languageEnglish (US)
Pages (from-to)788-793
Number of pages6
JournalNature
Volume424
Issue number6950
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Genome
Vertebrates
DNA Transposable Elements
Chromosomes, Human, Pair 7
Nucleic Acid Regulatory Sequences
Human Chromosomes
Cystic Fibrosis
Primates
Genes
Sequence Analysis
Rodentia

ASJC Scopus subject areas

  • General

Cite this

Thomas, J. W., Touchman, J. W., Blakesley, R. W., Bouffard, G. G., Beckstrom-Sternberg, S. M., Margulies, E. H., ... Green, E. D. (2003). Comparative analyses of multi-species sequences from targeted genomic regions. Nature, 424(6950), 788-793. https://doi.org/10.1038/nature01858

Comparative analyses of multi-species sequences from targeted genomic regions. / Thomas, J. W.; Touchman, J. W.; Blakesley, R. W.; Bouffard, G. G.; Beckstrom-Sternberg, Stephen 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.

In: Nature, Vol. 424, No. 6950, 2003, p. 788-793.

Research output: Contribution to journalArticle

Thomas, JW, Touchman, JW, Blakesley, RW, Bouffard, GG, Beckstrom-Sternberg, SM, Margulies, EH, Blanchette, M, Siepel, AC, Thomas, PJ, McDowell, JC, Maskeri, B, Hansen, NF, Schwartz, MS, Weber, RJ, Kent, WJ, Karolchik, D, Bruen, TC, Bevan, R, Cutler, DJ, Schwartz, S, Elnitski, L, Idol, JR, Prasad, AB, Lee-Lin, SQ, Maduro, VVB, Summers, TJ, Portnoy, ME, Dietrich, NL, Akhter, N, Ayele, K, Benjamin, B, Cariaga, K, Brinkley, CP, Brooks, SY, Granite, S, Guan, X, Gupta, J, Haghighi, P, Ho, SL, Huang, MC, Karlins, E, Laric, PL, Legaspi, R, Lim, MJ, Maduro, QL, Masiello, CA, Mastrian, SD, McCloskey, JC, Pearson, R, Stantripop, S, Tiongson, EE, Tran, JT, Tsurgeon, C, Vogt, JL, Walker, MA, Wetherby, KD, Wiggins, LS, Young, AC, Zhang, LH, Osoegawa, K, Zhu, B, Zhao, B, Shu, CL, De Jong, PJ, Lawrence, CE, Smit, AF, Chakravarti, A, Haussler, D, Green, P, Miller, W & Green, ED 2003, 'Comparative analyses of multi-species sequences from targeted genomic regions', Nature, vol. 424, no. 6950, pp. 788-793. https://doi.org/10.1038/nature01858
Thomas JW, Touchman JW, Blakesley RW, Bouffard GG, Beckstrom-Sternberg SM, Margulies EH et al. Comparative analyses of multi-species sequences from targeted genomic regions. Nature. 2003;424(6950):788-793. https://doi.org/10.1038/nature01858
Thomas, J. W. ; Touchman, J. W. ; Blakesley, R. W. ; Bouffard, G. G. ; Beckstrom-Sternberg, Stephen 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. In: Nature. 2003 ; Vol. 424, No. 6950. pp. 788-793.
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AU - Thomas, J. W.

AU - Touchman, J. W.

AU - Blakesley, R. W.

AU - Bouffard, G. G.

AU - Beckstrom-Sternberg, Stephen M

AU - Margulies, E. H.

AU - Blanchette, M.

AU - Siepel, A. C.

AU - Thomas, P. J.

AU - McDowell, J. C.

AU - Maskeri, B.

AU - Hansen, N. F.

AU - Schwartz, M. S.

AU - Weber, R. J.

AU - Kent, W. J.

AU - Karolchik, D.

AU - Bruen, T. C.

AU - Bevan, R.

AU - Cutler, D. J.

AU - Schwartz, S.

AU - Elnitski, L.

AU - Idol, J. R.

AU - Prasad, A. B.

AU - Lee-Lin, S. Q.

AU - Maduro, V. V B

AU - Summers, T. J.

AU - Portnoy, M. E.

AU - Dietrich, N. L.

AU - Akhter, N.

AU - Ayele, K.

AU - Benjamin, B.

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AU - Guan, X.

AU - Gupta, J.

AU - Haghighi, P.

AU - Ho, S. L.

AU - Huang, M. C.

AU - Karlins, E.

AU - Laric, P. L.

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AU - Lim, M. J.

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AU - Masiello, C. A.

AU - Mastrian, S. D.

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AU - Young, A. C.

AU - Zhang, L. H.

AU - Osoegawa, K.

AU - Zhu, B.

AU - Zhao, B.

AU - Shu, C. L.

AU - De Jong, P. J.

AU - Lawrence, C. E.

AU - Smit, A. F.

AU - Chakravarti, A.

AU - Haussler, D.

AU - Green, P.

AU - Miller, W.

AU - Green, E. D.

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