Direct determination of molecular haplotypes by chromosome microdissection

Article metrics

Abstract

Direct observation of haplotypes is still technically challenging. Here we report a method for the determination of haplotypes through chromosome microdissection. We determined human long-range chromosomal haplotypes with more than 98.85% accuracy at 24,245 genome-wide heterozygous single-nucleotide polymorphism (SNP) loci.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The principle and results for chromosome 5 of the 7DDNA haplotyping method.

References

  1. 1

    Levenstien, M.A., Ott, J. & Gordon, D. PLoS Genet. 2, e127 (2006).

  2. 2

    Marchini, J. et al. Am. J. Hum. Genet. 78, 437–450 (2006).

  3. 3

    Stephens, M. & Donnelly, P. Am. J. Hum. Genet. 73, 1162–1169 (2003).

  4. 4

    Ragoussis, J. Annu. Rev. Genomics Hum. Genet. 10, 117–133 (2009).

  5. 5

    Xiao, M. et al. Nat. Methods 6, 199–201 (2009).

  6. 6

    Yan, H. et al. Nature 403, 723–724 (2000).

  7. 7

    Douglas, J.A., Boehnke, M., Gillanders, E., Trent, J.M. & Gruber, S.B. Nat. Genet. 28, 361–364 (2001).

  8. 8

    Mitra, R.D. et al. Proc. Natl. Acad. Sci. USA 100, 5926–5931 (2003).

  9. 9

    Zhang, K. et al. Nat. Genet. 38, 382–387 (2006).

  10. 10

    Liu, N., Zhang, K. & Zhao, H. Adv. Genet. 60, 335–405 (2008).

  11. 11

    The International HapMap Consortium. Nature 426, 789–796 (2003).

  12. 12

    Hodge, S.E., Boehnke, M. & Spence, M.A. Nat. Genet. 21, 360–361 (1999).

  13. 13

    Highsmith, W.E. Jr., Meyer, K.J., Marley, V.M. & Jenkins, R.B. In Curr. Protoc. Hum. Genet. 3.6 (John Wiley and Sons, Inc., 2007).

  14. 14

    Tjio, J.H. & Levan, A. Hereditas 42, 1–6 (1956).

  15. 15

    Jurka, J. Trends Genet. 16, 418–420 (2000).

Download references

Acknowledgements

This work was supported by US National Institutes of Health grants (HL003676, RR014758, RR003034, NS45012 and HG004436), an American Heart Association grant (09GRNT2300003) and in part by the Medical Research Service of the Department of Veterans Affairs. K.Z. was supported by National Institutes of Health (GM074913). We thank S.J. Kittner, R.A. Kittles, G. Newman and G.H. Gibbons for reading and discussing the manuscript, and the people who donated blood samples and members of the International HapMap project.

Author information

L.M. performed experiments and data analysis. Y.X. and Q.W. assisted with microdissection experiments. H.H. assisted with cytogenetic experiments. L.M. and W.R. performed computational data analysis. Y.F. contributed to data analysis and manuscript preparation. K.Z. conducted statistical analysis. Q.S. designed the experiments, performed data analysis and wrote the manuscript.

Correspondence to Qing Song.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4, Supplementary Tables 1, 3–7 and Supplementary Notes 1–2 (PDF 227 kb)

Supplementary Table 2

The 7DDNA haplotype report. (XLS 5608 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading