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Evolutionary sequence comparisons using high-density oligonucleotide arrays

Abstract

We explored the utility of high-density oligonucleotide arrays (DMA chips) for obtaining sequence information from homologous genes in closely related species. Orthologues of the human BRCA1 exon 11, all approximately 3.4 kb in length and ranging from 98.2% to 83.5% nucleotide identity, were subjected to hybridization-based and conventional dideoxysequencing analysis. Retrospective guidelines for identifying high-fidelity hybridization-based sequence calls were formulated based upon dideoxysequencing results. Prospective application of these rules yielded base-calling with at least 98.8% accuracy over orthologous sequence tracts shown to have approximately 99% identity. For higher primate sequences with greater than 97% nucleotide identity, base-calling was made with at least 99.91 % accuracy covering a minimum of 97% of the sequence. Using a second-tier confirmatory hybridization chip strategy, shown in several cases to confirm the identity of predicted sequence changes, the complete sequence of the chimpanzee, gorilla and orangutan orthologues should be deducible solely through hybridization-based methodologies. Analysis of less highly conserved orthologues can still identify conserved nucleotide tracts of at least 15 nucleotides and can provide useful information for designing primers. DMA-chip based assays can be a valuable new technology for obtaining high-throughput cost-effective sequence information from related genomes.

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References

  1. Li, W.-H. Molecular evolution. (Sinauer Associates, Sunderland, Massachusetts, 1997).

  2. Tagle, D.A. et al. Embyonic ε and γ globin genes of a prosimian primate (Galago crassicaudatus) nucleotide and amino acid sequences, developmental regulation and phylogenetic footprints. J. Mol. Biol. 203, 439–455 (1988).

    Article  CAS  Google Scholar 

  3. Chee, M.S. et al. Accessing genetic information with high-density DNA arrays. Science 274, 610–614 (1996).

    Article  CAS  Google Scholar 

  4. Drmanac, R. et al. DNA sequence determination by hybridization: a strategy for efficient large-scale sequencing. Science 260, 1649–1652 (1993).

    Article  CAS  Google Scholar 

  5. Fodor, S.P.A. et al. Light-directed spatially addressable parallel chemical synthesis. Science 251, 767–773 (1991).

    Article  CAS  Google Scholar 

  6. Cronin, M.T. et al Cystic fibrosis mutation detection by hybridization to light-generated DNA probe arrays. Hum. Mut. 7, 244–255 (1996).

    Article  CAS  Google Scholar 

  7. Kozal, M.J. et al. Extensive polymorphisms observed in HIV-1 clade B protease gene using high density oligonucleotide arrays. Nature Med. 2, 753–759 (1996).

    Article  CAS  Google Scholar 

  8. Yershov, G. et al. DNA analysis and diagnostics on oligonucleotide microchips. Proc. Natal. Acad. Sci. USA 93, 4913–4918 (1996).

    Article  CAS  Google Scholar 

  9. Hacia, J.G. et al. Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis. Nature Genet. 14, 441–447 (1996).

    Article  CAS  Google Scholar 

  10. Lockhart, D. et al. Monitoring gene expression using high density oligonucleotide arrays. Nature Biotech. 14, 1675–1680 (1996).

    Article  CAS  Google Scholar 

  11. Shoemaker, D.D. et al Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar-coding strategy. Nature Genet. 14, 450–456 (1996).

    Article  CAS  Google Scholar 

  12. Milner, N. et al. Selecting effective antisense reagents on combinatorial oligonucleotide arrays. Nature Biotech. 15, 537–541 (1997).

    Article  CAS  Google Scholar 

  13. Miki, Y. et al A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).

    Article  CAS  Google Scholar 

  14. McConkey, E.H. & Goodman, M. A human genome evolution project is needed. Trends in Genet. 13, 350–351 (1997).

    Article  CAS  Google Scholar 

  15. Kruglyak, L. The use of a genetic map of biallelic markers in linkage studies. Nature Genet. 17, 21–24 (1997).

    Article  CAS  Google Scholar 

  16. Hoheisel, J.D. Sequence-independent and linear variation of oligonucleotide DNA binding stabilities. Nucleic Acids Res. 24, 430–432 (1996).

    Article  CAS  Google Scholar 

  17. Broude, N.E. Enhanced sequencing by hybridization. Proc. Natl. Acad. Sci. USA 91, 3072–3076 (1994).

    Article  CAS  Google Scholar 

  18. Szabo, C.I. et al. Human, canine, and murine BRCA1 genes: sequence comparison among species. Hum. Mol. Genet. 5, 1289–1298 (1996).

    Article  CAS  Google Scholar 

  19. Huang, X. On global sequence alignment. Comput Appl. Biosci. 10, 227–235 (1994).

    CAS  Google Scholar 

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Correspondence to Francis S. Collins.

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Hacia, J., Makalowski, W., Edgemon, K. et al. Evolutionary sequence comparisons using high-density oligonucleotide arrays. Nat Genet 18, 155–158 (1998). https://doi.org/10.1038/ng0298-155

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