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Nature Genetics
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The Fanconi anaemia group G geneFANCGis identical withXRCC9

Nature Geneticsvolume 20, pages281–283 (1998)Cite this article

Abstract

Fanconi anemia (FA) is an autosomal recessive disease with diverse clinical symptoms including developmental anomalies, bone marrow failure and early occurrence of malignancies1. In addition to spontaneous chromosome instability, FA cells exhibit cell cycle disturbances and hypersensitivity to cross-linking agents1. Eight complementation groups (A-H) have been distinguished2, each group possibly representing a distinct FA gene3. The genes mutated in patients of complementation groups A (FANCA; Refs4,5) and C (FANCC; ref.6) have been identified, andFANCD has been mapped to chromosome band 3p22-26 (ref.7). An additional FA gene has recently been mapped to chromosome 9p (ref.8). Here we report the identification of the gene mutated in group G,FANCG, on the basis of complementation of an FA-G cell line and the presence of pathogenic mutations in four FA-G patients. We identified the gene as humanXRCC9, a gene which has been shown to complement the MMC-sensitive Chinese hamster mutant UV40, and is suspected to be involved in DNA post-replication repair or cell cycle checkpoint control9,10. The gene is localized to chromosome band 9p13 (ref.9), corresponding with a known localization of an FA gene.

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Figure 1: Complementation of cross-linker hypersensitivity by pFAG9.
Figure 2: The 5' UTR ofFANCG cDNA inserts recovered from transfected MMC-resistant EUFA143.
Figure 3: Family FA15BER and detection of the IVS13-1G→C mutation inFANCG.
Figure 4:FANCG mRNA expression.

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ArticleOpen access09 September 2021

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References

  1. Auerbach, A.D., Buchwald, M. & Joenje, H. Fanconi anemia. inThe Genetic Basis of Human Cancer (eds Vogelstein, B. & Kinzler, K.W.) 317– 332 (McGraw-Hill, New York, 1998).

    Google Scholar 

  2. Joenje, H. et al. Evidence for at least eight Fanconi anemia genes. Am. J. Hum. Genet.61, 940–944 (1997).

    Article CAS  Google Scholar 

  3. Buchwald, M. Complementation groups: one or more per gene?Nature Genet. 11, 228–230 (1995).

    Article CAS  Google Scholar 

  4. Lo ten Foe, J.R. et al. Expression cloning of a cDNA for the major Fanconi anemia gene, FAA.Nature Genet.14, 320– 323 (1996).

    Article CAS  Google Scholar 

  5. The Fanconi anemia/Breast cancer consortium. Positional cloning of Fanconi anemia group A gene.Nature Genet. 14, 324–328 (1996).

  6. Strathdee, C.A., Gavish, H., Shannon, W.R. & Buchwald, M. Cloning of cDNAs for Fanconi's anaemia by functional complementation. Nature356, 763–767 (1992).

    Article CAS  Google Scholar 

  7. Whitney, M. et al. Microcell mediated chromosome transfer maps the Fanconi anemia group D gene to chromosome 3p.Nature Genet.11, 341–343 (1995).

    Article CAS  Google Scholar 

  8. Saar, K.et al. Localisation of a Fanconi anaemia gene to chromosome 9p. Eur. J. Hum. Genet.6, 501–508 (1998).

    Article CAS  Google Scholar 

  9. Liu, N. et al. The humanXRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells.Proc. Natl Acad. Sci. USA94, 9232–9237 (1997).

    Article CAS  Google Scholar 

  10. Busch, D.B. et al. A CHO mutant, UV40, that is sensitive to diverse mutagens and represents a new complementation group of mitomycin C sensitivity. Mutat. Res.363, 209–221 (1996).

    Article  Google Scholar 

  11. Ishida, R. & Buchwald, M. Susceptibility of Fanconi's anemia lymphoblasts to DNA cross-linking and alkylating agents.Cancer Res.42, 4000–4006 (1982).

    CAS PubMed  Google Scholar 

  12. Schindler, D. & Hoehn, H. Fanconi anemia mutation causes cellular susceptibility to ambient oxygen.Am. J. Hum. Genet. 43, 429–435 (1988).

    CAS PubMed PubMed Central  Google Scholar 

  13. Kupfer, G.M. et al. The Fanconi anemia proteins, FAA and FAC, interact to form a nuclear complex.Nature Genet.17, 487–490 (1997).

    Article CAS  Google Scholar 

  14. Hoatlin, M.E. et al. The Fanconi anemia group C gene product is located both in the nucleus and cytoplasm of human cells.Blood91, 1418–1425 (1998).

    CAS PubMed  Google Scholar 

  15. Carreau, M. & Buchwald, M. Fanconi's anemia: what have we learned from the genes so far?Mol. Med. Today4, 201–206 (1998).

    Article CAS  Google Scholar 

  16. Kinzler, K.W. & Vogelstein, B. Gatekeepers and caretakers. Nature386, 761–763 (1997).

    Article CAS  Google Scholar 

  17. Levran, O. et al. Sequence variation in the Fanconi anemia geneFAA.Proc. Natl Acad. Sci. USA94, 13051– 13056 (1997).

    Article CAS  Google Scholar 

  18. Auerbach, A.D. & Verlander, P.C. Disorders of DNA replication and repair.Curr. Opin. Pediatr. 9, 600–616 (1997).

    Article CAS  Google Scholar 

  19. Chen, M.et al. Inactivation ofFac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anemia. Nature Genet.12, 448–451 (1996).

    Article CAS  Google Scholar 

  20. Whitney, M.A. et al. Germ cell defects and hematopoietic hypersensitivity to γ interferon in mice with a targeted disruption of the Fanconi anemia C gene.Blood88, 49–58 (1996).

    CAS PubMed  Google Scholar 

  21. Strathdee, C.A., Duncan, A.M.V. & Buchwald, M. Evidence for at least four Fanconi anemia genes including FACC on chromosome 9.Nature Genet.1, 196–198 (1992).

    Article CAS  Google Scholar 

  22. Joenje, H. et al. Classification of Fanconi anemia patients by complementation analysis: evidence for a fifth genetic subtype.Blood 86, 2156–2160 (1995).

    CAS PubMed  Google Scholar 

  23. Savov, A., Angelicheva, D., Jorfanova, A., Eigel, A. & Kalaydjieva, L. High percentage acrylamide gels improve resolution in SSCP analysis.Nucleic Acids Res. 20, 6741–6742 (1992).

    Article CAS  Google Scholar 

  24. Moshell, A.N., Tarone, R.E., Newfield, S.A., Andrews, A.D. & Robbins, J.H. A simple and rapid method for evaluating the survival of xeroderma pigmentosum lymphoid lines after irradiation with ultraviolet light.In Vitro17, 299–307 (1981).

    Article CAS  Google Scholar 

  25. Seyschab, H. et al. Comparative evaluation of diepoxybutane sensitivity and cell cycle blockage in the diagnosis of Fanconi anemia.Blood 85, 2233–2237 (1995).

    CAS PubMed  Google Scholar 

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Acknowledgements

We thank R. Dietrich and the FA families who participated in this research project, without whose cooperation this study would have been impossible. We are grateful to B. Schmalenberger, W. Ebell, U. Schulte-Overberg-Schmidt and U. Glöckel for referring patients. We also thank J. Steltenpool and L. van der Weel for technical assistance. This project was supported by the Dutch Cancer Society (project VU-97-1565), the Fanconi Anemia Research Fund Inc., the Commission of the European Union (EUFAR contract PL931562), the National Institutes of Health (HL50131), the Medical Research Council of Canada (MRC) and the Fritz-Thyssen-Stiftung (1997/2061).

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Author notes

  1. Johan P. de Winter and Quinten Waisfisz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Human Genetics, Free University, Van der Boechorststraat 7, Amsterdam, NL-1081 BT, The Netherlands

    Johan P. de Winter, Quinten Waisfisz, Martin A. Rooimans, Carola G.M. van Berkel, Jan C. Pronk, Fré Arwert & Hans Joenje

  2. Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue

    Lucine Bosnoyan-Collins, Noa Alon, Madeleine Carreau & Manuel Buchwald

  3. Department of Molecular and Medical Genetics, The University of Toronto, Toronto, Ontario, Canada

    Lucine Bosnoyan-Collins, Noa Alon, Madeleine Carreau & Manuel Buchwald

  4. Institut für Humangenetik, Charité-Campus Virchow-Klinikum, Humboldt Universität Berlin, Augustenburger Platz 1, Berlin, D-13353, Germany

    Olaf Bender, Ilja Demuth & Martin Digweed

  5. Institut für Humangenetik, Universität Würzburg, Biozentrum Am Hubland, Würzburg, D-8700, Germany

    Detlev Schindler & Holger Hoehn

Authors
  1. Johan P. de Winter

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  2. Quinten Waisfisz

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  4. Carola G.M. van Berkel

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  5. Lucine Bosnoyan-Collins

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  7. Madeleine Carreau

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Correspondence toHans Joenje.

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de Winter, J., Waisfisz, Q., Rooimans, M.et al. The Fanconi anaemia group G geneFANCGis identical withXRCC9.Nat Genet20, 281–283 (1998). https://doi.org/10.1038/3093

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