Confirmation and fine mapping of chromosomal regions influencing peak bone mass in mice

Robert F. Klein, Amy S. Carlos, Kristina A. Vartanian, Virginia K. Chambers, Renn J. Turner, Tamara J. Phillips, John K. Belknap, Eric S. Orwoll

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (RI-BXD). The distribution of BMD values among these strains indicated strong genetic influences and a number of chromosomal sites linked to BMD were identified provisionally. Using three additional independent mapping populations derived from the same progenitors, we have confirmed loci on chromosomes 1, 2, and 4, and 11 that contain genes that influence peak BMD. Using a novel fine-mapping approach (RI segregation testing [RIST]), we have substantially narrowed two of the BMD-related chromosomal regions and in the process eliminated a number of candidate genes. The homologous regions in the human genome for each of these murine QTLs have been identified in recent human genetic studies. In light of this, we believe that findings in mice should aid in the identification of specific candidate genes for study in humans.

Original languageEnglish (US)
Pages (from-to)1953-1961
Number of pages9
JournalJournal of Bone and Mineral Research
Volume16
Issue number11
DOIs
StatePublished - 2001

Keywords

  • Bone mineral density
  • Heredity
  • Osteoporosis
  • Quantitative trait
  • Quantitative trait locus analysis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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