Brief Communication | Published:

A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15

Nature Genetics volume 39, pages 11971199 (2007) | Download Citation

Subjects

Abstract

F cells measure the presence of fetal hemoglobin, a heritable quantitative trait in adults that accounts for substantial phenotypic diversity of sickle cell disease and β thalassemia. We applied a genome-wide association mapping strategy to individuals with contrasting extreme trait values and mapped a new F cell quantitative trait locus to BCL11A, which encodes a zinc-finger protein, on chromosome 2p15. The 2p15 BCL11A quantitative trait locus accounts for 15.1% of the trait variance.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Hemoglobin 22, 401–414 (1998).

  2. 2.

    , , & (eds.). Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management (Cambridge Univ. Press, Cambridge, 2001).

  3. 3.

    Blood 107, 435–443 (2006).

  4. 4.

    et al. Blood 95, 342–346 (2000).

  5. 5.

    et al. GeneScreen 1, 9–14 (2000).

  6. 6.

    et al. Proc. Natl. Acad. Sci. USA 104, 11346–11351 (2007).

  7. 7.

    & Twin Res. 5, 440–443 (2002).

  8. 8.

    , , & Behav. Genet. 35, 219–228 (2005).

  9. 9.

    & Biometrics 55, 997–1004 (1999).

  10. 10.

    , & PLoS Genet. 2, e190 (2006) (doi:10.1371/journal.pgen.0020190).

  11. 11.

    et al. Nat. Genet. 12, 58–64 (1996).

  12. 12.

    et al. Nat. Immunol. 4, 525–532 (2003).

  13. 13.

    International HapMap Consortium. Nature 437, 1299–1320 (2005).

  14. 14.

    , & Am. J. Hum. Genet. 66, 279–292 (2000).

  15. 15.

    , & Arch. Biochem. Biophys. 434, 316–325 (2005).

Download references

Acknowledgements

We thank C. Steward for help in preparation of the manuscript. This work was supported by a grant from the UK Medical Research Council (MRC; G0000111 and ID 51640) to S.L.T. and by the French Ministry of Higher Education and Research (M.L.). Twins UK is supported by the Wellcome Trust and Framework V EU (European Union) grant 'Genome EU Twin'.

Author information

Affiliations

  1. King's College London School of Medicine, Division of Gene and Cell Based Therapy, King's Denmark Hill Campus, London SE5 9PJ, UK.

    • Stephan Menzel
    • , Helen Rooks
    • , Steve Best
    •  & Swee Lay Thein
  2. University of California at Irvine, Epidemiology Division, Department of Medicine, Irvine, California 92697-7550, USA.

    • Chad Garner
  3. Centre National de Génotypage, Institut Génomique, Commissariat à l'Energie Atomique, 91006 Evry, France.

    • Ivo Gut
    • , Fumihiko Matsuda
    • , Masao Yamaguchi
    • , Simon Heath
    • , Mario Foglio
    • , Diana Zelenika
    • , Anne Boland
    •  & Mark Lathrop
  4. King's College London School of Medicine, Division of Genetics and Molecular Medicine, St. Thomas' Hospital, London SE1 7EH, UK.

    • Tim D Spector
  5. The Wellcome Trust Centre for Human Genetics, Department of Cardiovascular Medicine, University of Oxford, Headington, Oxford OX3 7BN, UK.

    • Martin Farrall
  6. King's College Hospital, Department of Haematological Medicine, Denmark Hill, London SE5 9RS, UK.

    • Swee Lay Thein

Authors

  1. Search for Stephan Menzel in:

  2. Search for Chad Garner in:

  3. Search for Ivo Gut in:

  4. Search for Fumihiko Matsuda in:

  5. Search for Masao Yamaguchi in:

  6. Search for Simon Heath in:

  7. Search for Mario Foglio in:

  8. Search for Diana Zelenika in:

  9. Search for Anne Boland in:

  10. Search for Helen Rooks in:

  11. Search for Steve Best in:

  12. Search for Tim D Spector in:

  13. Search for Martin Farrall in:

  14. Search for Mark Lathrop in:

  15. Search for Swee Lay Thein in:

Contributions

S.M. performed research, analyzed data and wrote the paper; C.G. analyzed data; M.Y. and M. Foglio performed bioinformatics analyses; I.G. and S.H. performed genome-wide association genotyping; D.Z., A.B., H.R., and S.B. performed research; T.D.S. contributed material; M. Farrall performed statistical genetic analysis and wrote the paper; M.L. codirected the research, analyzed data and wrote the paper; S.L.T. codirected the research and wrote the paper.

Corresponding author

Correspondence to Swee Lay Thein.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Methods, Supplementary Tables 1–4, Supplementary Figures 1–3

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng2108

Further reading