Research-Article

You have full text access to this OnlineOpen article

Genome-Wide Haplotype Association Mapping in Mice Identifies a Genetic Variant in CER1 Associated With BMD and Fracture in Southern Chinese Women†‡

  1. Paul LF Tang1,2,
  2. Ching-Lung Cheung2,3,
  3. Pak C Sham4,5,
  4. Philip McClurg6,
  5. Bob Lee1,
  6. Shut-Yan Chan1,
  7. David K Smith1,
  8. Julian A Tanner1,5,
  9. Andrew I Su6,
  10. Kathryn SE Cheah1,5,
  11. Annie WC Kung2,3,
  12. You-Qiang Song1,5,*

Article first published online: 29 DEC 2008

DOI: 10.1359/jbmr.081258

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 24, Issue 6, pages 1013–1021, June 2009

Additional Information

How to Cite

Tang, P. L., Cheung, C.-L., Sham, P. C., McClurg, P., Lee, B., Chan, S.-Y., Smith, D. K., Tanner, J. A., Su, A. I., Cheah, K. S., Kung, A. W. and Song, Y.-Q. (2009), Genome-Wide Haplotype Association Mapping in Mice Identifies a Genetic Variant in CER1 Associated With BMD and Fracture in Southern Chinese Women. J Bone Miner Res, 24: 1013–1021. doi: 10.1359/jbmr.081258

Author Information

  1. 1

    Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

  2. 2

    These authors contributed equally to this study

  3. 3

    Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

  4. 4

    Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

  5. 5

    Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

  6. 6

    Genomics Institute of the Novartis Research Foundation, San Diego, California, USA

*Address correspondence to: You-Qiang Song, Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

  1. †

    The authors state that they have no conflicts of interest.

  2. ‡

    Published online on December 29, 2008

Publication History

  1. Issue published online: 4 DEC 2009
  2. Article first published online: 29 DEC 2008
  3. Manuscript Accepted: 23 DEC 2008
  4. Manuscript Revised: 10 JUL 2008
  5. Manuscript Received: 1 APR 2008

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (764K)

REFERENCES

  • 1
    Kanis JA 1994 Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. WHO Study Group. Osteoporos Int 4: 368–381.
  • 2
    Huang QY, Kung AW 2006 Genetics of osteoporosis. Mol Genet Metab 88: 295–306.
  • 3
    Orwoll ES, Belknap JK, Klein RF 2001 Gender specificity in the genetic determinants of peak bone mass. J Bone Miner Res 16: 1962–1971.
    Direct Link:
  • 4
    Klein RF, Mitchell SR, Phillips TJ, Belknap JK, Orwoll ES 1998 Quantitative trait loci affecting peak bone mineral density in mice. J Bone Miner Res 13: 1648–1656.
    Direct Link:
  • 5
    Klein OF, Carlos AS, Vartanian KA, Chambers VK, Turner EJ, Phillips TJ, Belknap JK, Orwoll ES 2001 Confirmation and fine mapping of chromosomal regions influencing peak bone mass in mice. J Bone Miner Res 16: 1953–1961.
    Direct Link:
  • 6
    Klein RF, Allard J, Avnur Z, Nikolcheva T, Rotstein D, Carlos AS, Shea M, Waters RV, Belknap JK, Peltz G, Orwoll ES 2004 Regulation of bone mass in mice by the lipoxygenase gene Alox15. Science 303: 229–232.
  • 7
    Urano T, Shiraki M, Fujita M, Hosoi T, Orimo H, Ouchi Y, Inoue S 2005 Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5′-flanking region (-5229G/A) with bone mineral density. J Bone Miner Metab 23: 226–230.
  • 8
    Cheung CL, Chan V, Kung AW 2008 A Differential Association of ALOX15 Polymorphisms with Bone Mineral Density in Pre- and Post-Menopausal Women. Hum Hered 65: 1–8.
  • 9
    Kenneth P, Janan TE 2000 A mouse phenome project. Mamm Genome V11: 715–717.
  • 10
    Grupe A, Germer S, Usuka J, Aud D, Belknap JK, Klein RF, Ahluwalia MK, Higuchi R, Peltz G 2001 In silico mapping of complex disease-related traits in mice. Science 292: 1915–1918.
  • 11
    Chesler EJ, Rodriguez-Zas SL, Mogil JS 2001 In silico mapping of mouse quantitative trait loci. Science 294: 2423.
  • 12
    Darvasi A 2001 In silico mapping of mouse quantitative trait loci. Science 294: 2423.
  • 13
    Liao G, Wang J, Guo J, Allard J, Cheng J, Ng A, Shafer S, Puech A, McPherson JD, Foernzler D, Peltz G, Usuka J 2004 In silico genetics: Identification of a functional element regulating H2-Ealpha gene expression. Science 306: 690–695.
  • 14
    Pletcher MT, McClurg P, Batalov S, Su AI, Barnes SW, Lagler E, Korstanje R, Wang X, Nusskern D, Bogue MA, Mural RJ, Paigen B, Wiltshire T 2004 Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse PLoS Biol. 2: e393.
  • 15
    McClurg P, Pletcher MT, Wiltshire T, Su AI 2006 Comparative analysis of haplotype association mapping algorithms. BMC Bioinformatics 7: 61.
  • 16
    Wang J, Liao G, Usuka J, Peltz G 2005 Computational genetics: From mouse to human ? Trends Genet 21: 526–532.
  • 17
    van der Laan MJ, Dudoit S, Pollard KS 2004 Multiple testing. Part II. Step-down procedures for control of the family-wise error rate. UC Berkeley Division of Biostatistics Working Paper 139. Available at http://www.bepress.com/ucbbiostat/paper139 .
  • 18
    Genant HK, Wu CY, van Kuijk C, Nevitt MC 1993 Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8: 1137–1148.
    Direct Link:
  • 19
    Barrett JC, Fry B, Maller J, Daly MJ 2005 Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics 21: 263–265.
  • 20
    Tsang KY, Chan D, Cheslett D, Chan WCW, So CL, Melhado IG, Chan TWY, Kwan KM, Hunziker EB, Yamada Y, Bateman JF, Cheung KMC, Cheah KSE 2007 Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function. PLoS Biol 5: e44.
  • 21
    Bogue MA, Grubb SC, Maddatu TP, Bult CJ 2007 Mouse Phenome Database (MPD). Nucleic Acids Res 35: D643–D649.
  • 22
    Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, De Robertis EM 1999 The head inducer cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature 397: 707–710.
  • 23
    Shawlot W, Deng JM, Behringer RR 1998 Expression of the mouse cerberus-related gene, Cerr1, suggests a role in anterior neural induction and somitogenesis. Proc Natl Acad Sci USA 95: 6198–6203.
  • 24
    Simic P, Culej JB, Orlic I, Grgurevic L, Draca N, Spaventi R, Vukicevic S 2006 Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. J Biol Chem 281: 25509–25521.
  • 25
    Ng MYM, Sham PC, Paterson AD, Chan V, Kung AWC 2006 Effect of Environmental Factors and Gender on the Heritability of Bone Mineral Density and Bone Size. Ann Hum Genet 70: 428–438.
    Direct Link:
  • 26
    Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D 2002 The Structure of Haplotype Blocks in the Human Genome. Science 296: 2225–2229.
  • 27
    Purcell S, Cherny SS, Sham PC 2003 Genetic power calculator: Design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19: 149–150.
  • 28
    Gazzerro E, Pereira RC, Jorgetti V, Olson S, Economides AN, Canalis E 2005 Skeletal overexpression of gremlin impairs bone formation and causes osteopenia. Endocrinology 146: 655–665.
  • 29
    Abiola O, Angel JM, Avner P, Bachmanov AA, Belknap JK, Bennett B, Blankenhorn EP, Blizard DA, Bolivar V, Brockmann GA, Buck KJ, Bureau JF, Casley WL, Chesler EJ, Cheverud JM, Churchill GA, Cook M, Crabbe JC, Crusio WE, Darvasi A, de Haan G, Dermant P, Doerge RW, Elliot RW, Farber CR, Flaherty L, Flint J, Gershenfeld H, Gibson JP, Gu J, Gu W, Himmelbauer H, Hitzemann R, Hsu HC, Hunter K, Iraqi FF, Jansen RC, Johnson TE, Jones BC, Kempermann G, Lammert F, Lu L, Manly KF, Matthews DB, Medrano JF, Mehrabian M, Mittlemann G, Mock BA, Mogil JS, Montagutelli X, Morahan G, Mountz JD, Nagase H, Nowakowski RS, O'Hara BF, Osadchuk AV, Paigen B, Palmer AA, Peirce JL, Pomp D, Rosemann M, Rosen GD, Schalkwyk LC, Seltzer Z, Settle S, Shimomura K, Shou S, Sikela JM, Siracusa LD, Spearow JL, Teuscher C, Threadgill DW, Toth LA, Toye AA, Vadasz C, Van Zant G, Wakeland E, Williams RW, Zhang HG, Zou F 2003 The nature and identification of quantitative trait loci: A community's view. Nat Rev Genet 4: 911–916.
  • 30
    Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, Paigen K 2005 Evidence of a large-scale functional organization of mammalian chromosomes. PLoS Genet 1: e33.
  • 31
    Chung UI, Schipani E, McMahon AP, Kronenberg HM 2001 Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. J Clin Invest 107: 295–304.
  • 32
    Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E, McAnally J, Pomajzl C, Shelton JM, Richardson JA, Karsenty G, Olson EN 2004 Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 119: 555–566.
  • 33
    Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, Wu H, Yu K, Ornitz DM, Olson EN, Justice MJ, Karsenty G 2004 A twist code determines the onset of osteoblast differentiation. Dev Cell 6: 423–435.
  • 34
    Deregowski V, Gazzerro E, Priest L, Rydziel S, Canalis E 2006 Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-catenin but not bone morphogenetic protein signaling. J Biol Chem 281: 6203–6210.
  • 35
    Pearce JJH, Penny G, Rossant J 1999 A mouse cerberus/dan-related gene family. Dev Biol 209: 98–110.
  • 36
    Uitterlinden AG, Arp PP, Paeper BW, Charmley P, Proll S, Rivadeneira F, Fang Y, van Meurs JBJ, Britschgi TB, Latham JA, Schatzman RC, Pols HAP, Brunkow ME 2004 Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. Am J Hum Genet 75: 1032–1045.
  • 37
    Edgar R, Domrachev M, Lash AE 2002 Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207–210.
  • 38
    Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E 2003 Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest 112: 924–934.
  • 39
    Devlin RD, Du Z, Pereira RC, Kimble RB, Economides AN, Jorgetti V, Canalis E 2003 Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology 144: 1972–1978.
  • 40
    Rifas L 2007 The role of noggin in human mesenchymal stem cell differentiation. J Cell Biochem 100: 824–834.
    Direct Link:
  • 41
    Itoh K, Udagawa N, Katagiri T, Iemura S, Ueno N, Yasuda H, Higashio K, Quinn JMW, Gillespie MT, Martin TJ, Suda T, Takahashi N 2001 Bone morphogenetic protein 2 stimulates osteoclast differentiation and survival supported by receptor activator of nuclear factor-?B ligand. Endocrinology 142: 3656–3662.
  • 42
    Abe E, Yamamoto M, Taguchi Y, Lecka-Czernik B, O'Brien CA, Economides AN, Stahl N, Jilka RL, Manolagas SC 2000 Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: Antagonism by noggin. J Bone Miner Res 15: 663–673.
  • 43
    Okamoto M, Murai J, Yoshikawa H, Tsumaki N 2006 Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. J Bone Miner Res 21: 1022–1033.
    Direct Link:
  • 44
    Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D 2007 Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8 (Suppl 1): S14.
View Full Article (HTML) Get PDF (764K)