期刊
BONE
卷 55, 期 1, 页码 222-229出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2013.02.014
关键词
Osteoporosis; Femoral traits; Bone morphology; Diet
资金
- National Institutes of Diabetes and Digestive and Kidney Diseases [DK-076050, AR-057759]
- National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056350]
Osteoporosis, characterized by low levels of bone mineral density (BMD), is a prevalent medical condition in humans. We investigated its genetic and environmental basis by searching for quantitative trait loci (QTLs) affecting six skeletal (including three BMD) traits in a G(10) advanced intercross population produced from crosses of mice from the inbred strain C57BL/6J with mice from a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a matched control diet throughout the study, allowing us to test for QTL by diet interactions for the skeletal traits. Our genome scan uncovered a number of QTLs, the great majority of which were different from QTLs previously found for these same traits in an earlier (G(4)) generation of the same intercross. Further, the confidence intervals for the skeletal trait QTLs were reduced from an average of 18.5 Mb in the G(4) population to an equivalent of about 9 Mb in the G(10) population. We uncovered a total of 50 QTLs representing 32 separate genomic sites affecting these traits, with a distal region on chromosome 1 harboring several QTLs with large effects on the BMD traits. One QTL was located on chromosome 5 at 4.0 Mb with a confidence interval spanning from 4.0 to 4.6 Mb. Only three protein coding genes reside in this interval, and one of these, Cyp51, is an attractive candidate as others have shown that developing Cyp51 knockout embryos exhibit shortened and bowed limbs and synotosis of the femur and tibia. Several QTLs showed significant interactions with sex, although only two QTLs interacted with diet, both affecting only mice fed the high-fat diet. (C) 2013 Elsevier Inc. All rights reserved.
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