A quantitative trait locus for normal variation in forearm bone mineral density in pedigreed baboons maps to the ortholog of human chromosome 11q.
Baboons share many anatomical, physiological, and developmental characteristics with humans that make them excellent models for human bone maintenance and turnover. We conducted statistical genetic analyses, including a whole-genome linkage screen, of dual-energy x-ray absorptiometry-acquired measures of areal bone mineral density (aBMD), currently the most reliable single predictor of susceptibility to osteoporotic fracture in humans, from three forearm sites on the radius and ulna of 667 pedigreed baboons. We used a maximum likelihood-based variance decomposition approach to detect and quantify the effects of genes on normal variation in aBMD in the forearm of these baboons and to localize these effects to chromosomal regions. We estimated significant heritability for aBMD at all three sites and found evidence for a quantitative trait locus (QTL) contributing significantly to the genetic effects on this trait in a region of the baboon genome homologous to human chromosome 11q12-13. This first reported genome-wide linkage screen in a nonhuman primate for QTLs affecting forearm aBMD provides important cross-species replication of a QTL found in humans. The concordance of our results in a nonhuman primate with those reported for humans provides strong evidence that a gene (or genes) in this region affects normal variation in BMD.
Havill
L M
LM
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, Texas 78245-0549, USA. lhavill@darwin.sfbr.org
Mahaney
M C
MC
Cox
L A
LA
Morin
P A
PA
Joslyn
G
G
Rogers
J
J
D000818:Animals; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005542:Forearm; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D010215:Papio / Q000235:genetics*; D010375:Pedigree; D040641:Quantitative Trait Loci