Abstract
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40–50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants.
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References
Beales, P. Curr. Opin. Genet. Dev. 15, 315–323 (2005).
Nishimura, D.Y. et al. Am. J. Hum. Genet. 77, 1021–1033 (2005).
Hichri, H. et al. Eur. J. Hum. Genet. 13, 607–616 (2005).
Katsanis, N. Hum. Mol. Genet. 13, R65–R71 (2004).
Katsanis, N. et al. Science 293, 2256–2259 (2001).
Ansley, S.J. et al. Nature 425, 628–633 (2003).
Ross, A.J. et al. Nat. Genet. 37, 1135–1140 (2005).
Blacque, O. et al. Genes Dev. 18, 1630–1642 (2004).
Kulaga, H.M. et al. Nat. Genet. 36, 994–998 (2004).
Kim, J.C. et al. J. Cell Sci. 118, 1007–1020 (2005).
Ditzel, L. et al. Cell 93, 125–138 (1998).
Badano, J.L. et al. Nature 439, 326–330 (2005).
Fan, Y. et al. Nat. Genet. 36, 989–993 (2004).
Chiang, A.P. et al. Am. J. Hum. Genet. 75, 475–484 (2004).
Li, J.B. et al. Cell 117, 541–552 (2004).
Acknowledgements
We thank the BBS families described here for their support and cooperation. We also thank the Centre National de Genotypage of Evry and the bioinformatics and microarray departments of the Institut de Génétique et de Biologie Moléculaire et Cellulaire, especially C. Thibault. In addition, we thank S. Fisher for continued advice on our zebrafish experiments. We acknowledge the financial support of the Programme Hospitalier de Recherche Clinique National 2002, RETINA France, Lion's Club du Kochersberg, Fédération des Maladies Orphelines and the Programme National de Recherches sur la Vision-Institut National de la Santé et de la Recherche Médicale (all to H.D.). This study was also funded with grants from the US National Institute of Child Health and Development (N.K.), the US National Institute of Diabetes, Digestive and Kidney disorders (N.K.), the Polycystic Kidney Disease Foundation (P.L.B., N.K.) and the Newlife (P.L.B.). P.L.B. is a Senior Wellcome Trust Fellow. R.A.L. is a Senior Scientific Investigator of Research to Prevent Blindness (New York), which provided unrestricted funds for these investigations.
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Supplementary information
Supplementary Fig. 1
C91fsX95 is an ancient mutation encompassed by a conserved haplotype block. (PDF 96 kb)
Supplementary Fig. 2
Comparative sequence identities and similarities of known BBS genes. (PDF 215 kb)
Supplementary Table 1
Mutations detected in BBS10. (PDF 89 kb)
Supplementary Table 2
Likely polymorphisms detected in BBS10. (PDF 56 kb)
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Stoetzel, C., Laurier, V., Davis, E. et al. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet 38, 521–524 (2006). https://doi.org/10.1038/ng1771
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DOI: https://doi.org/10.1038/ng1771
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