1. Bone. 2006 Jul;39(1):93-9. Epub 2006 Feb 3.
Identification of a quantitative trait locus on rat chromosome 4 that is strongly
linked to femoral neck structure and strength.
Alam I(1), Sun Q, Liu L, Koller DL, Fishburn T, Carr LG, Econs MJ, Foroud T,
Turner CH.
Author information:
(1)Department of Orthopaedic Surgery, Indiana University School of Medicine,
Indianapolis, IN 46202, USA.
Risk factors for osteoporotic hip fracture include reduced bone mineral density
and poor structure of the femoral neck, both of which are heritable traits.
Previously, we showed that despite similar body size, Fischer 344 (F344) rats
have significantly different skeletal traits compared with Lewis (LEW) rats. To
identify a gene or genes regulating fracture risk at the femoral neck, we mapped
quantitative trait loci (QTL) for femoral neck density and structure phenotypes
using a 595 F2 progeny derived from the inbred F344 and LEW strains of rats.
Femoral neck phenotypes included volumetric bone mineral density (vBMD), neck
width, femoral neck cross-sectional area and polar moment of inertia (Ip). A
20-cM genome-wide scan was performed using 118 microsatellite markers and linkage
analysis was conducted to identify chromosomal regions harbor QTL for femoral
neck phenotypes. Strong evidence of linkage (P<0.01) to femoral neck vBMD was
observed on chromosomes (Chrs) 1, 2, 4, 5, 7, 10 and 15. QTL affecting femoral
neck structure and biomechanical properties were detected only on Chr 4 where the
F344 alleles were shown to improve femoral neck structure, whereas these alleles
had no effect on bone measurements at the lumbar spine and only modest effects at
the femoral midshaft. In contrast, QTL on Chrs 1, 2 and 10 affected multiple
skeletal sites. Several QTL regions in this study are homologous to human
chromosomal regions, where linkage to femoral neck and related phenotypes has
been reported previously. These findings represent an important first step in
localizing and identifying genes that influence hip fragility.
PMID: 16461031 [PubMed - indexed for MEDLINE]
PUBMED: 16461031
Find other GeneSets from this publication
GeneWeaver