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Cross-Species Replication of a Serum Osteocalcin Quantitative Trait Locus on Human Chromosome 16q in Pedigreed Baboons

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Abstract

Osteocalcin (OC), a serum marker of bone formation, in its intact form reflects osteoblast activity. It is of interest to clinicians and bone biologists due to easy measurability and potential utility as an identifier of those at risk for fracture and other complications associated with bone metabolism disorders. The only published linkage study in humans shows significant evidence for a quantitative trait locus (QTL) affecting OC levels on 16q. We used the baboon, a primate model for skeletal maintenance and turnover, to detect and quantify the effects of genes on serum OC levels and to localize chromosomal regions harboring the responsible loci. We assayed OC levels in 591 pedigreed animals, assessed OC heritability, and conducted a genomewide linkage scan for evidence of QTLs affecting this phenotype. Heritability in these baboons is 0.24. Suggestive linkage is evident with markers in a region homologous to human chromosome 16q. This first genomewide linkage scan in a nonhuman primate for QTLs affecting bone formation as reflected by OC levels provides cross-species replication of the QTL on chromosome 16q previously localized in humans. Given the concordance of results of the only two genome scans for this trait in two primate species, further studies of this region are warranted.

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Acknowledgments

This research was made possible in part by support in the form of a collaborative research contract with AxyS Pharmaceuticals, Inc. (formerly Sequana Therapeutics, Inc.), and research grants from the National Institutes of Health (F32 AR049694, P01 HL28972, R01 HL54141, R01 RR008781, and R01 MH59490). The authors gratefully acknowledge the technical contributions and support of the following persons: K.D. Carey, D.E. Newman, K.S. Rice, T. Riley, E. Rodriguez, E. Windhorst, and S.M. Witte.

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Authors and Affiliations

  1. Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX, 78245-0549, USA

    L. M. Havill, L. A. Cox, J. Rogers & M. C. Mahaney

  2. Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, 78245-0549, USA

    J. Rogers & M. C. Mahaney

Authors
  1. L. M. Havill
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  2. L. A. Cox
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  3. J. Rogers
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  4. M. C. Mahaney
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Correspondence to L. M. Havill.

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Havill, L.M., Cox, L.A., Rogers, J. et al. Cross-Species Replication of a Serum Osteocalcin Quantitative Trait Locus on Human Chromosome 16q in Pedigreed Baboons. Calcif Tissue Int 77, 205–211 (2005). https://doi.org/10.1007/s00223-005-0056-1

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  • DOI: https://doi.org/10.1007/s00223-005-0056-1

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