NDLI: An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

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Analysis of CYP27B1, Encoding 25-Hydroxyvitamin D-1α-Hydroxylase, as a Candidate Tumor Suppressor Gene in Primary and Severe Secondary/Tertiary Hyperparathyroidism

An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

Successful Skeletal Aging: A Marker of Low Fracture Risk and Longevity. The Study of Osteoporotic Fractures (SOF)

Year: 2008, Volume: 23

Year: 2007, Volume: 23

An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

Content Provider	PubMed Central
Author	Farber, Charles R. Nas, Atila Van Anatole, Ghazalpour Aten, Jason E. Doss, Sudheer Sos, Brandon Schadt, Eric E. Leslie, Ingram-drake Davis, Richard C. Horvath, Steve Smith, Desmond J. Drake, Thomas A. Lusis, Aldons J.
Copyright Year	2009
Abstract	Numerous quantitative trait loci (QTLs) affecting bone traits have been identified in the mouse; however, few of the underlying genes have been discovered. To improve the process of transitioning from QTL to gene, we describe an integrative genetics approach, which combines linkage analysis, expression QTL (eQTL) mapping, causality modeling, and genetic association in outbred mice. In C57BL/6J × C3H/HeJ (BXH) F2 mice, nine QTLs regulating femoral BMD were identified. To select candidate genes from within each QTL region, microarray gene expression profiles from individual F2 mice were used to identify 148 genes whose expression was correlated with BMD and regulated by local eQTLs. Many of the genes that were the most highly correlated with BMD have been previously shown to modulate bone mass or skeletal development. Candidates were further prioritized by determining whether their expression was predicted to underlie variation in BMD. Using network edge orienting (NEO), a causality modeling algorithm, 18 of the 148 candidates were predicted to be causally related to differences in BMD. To fine-map QTLs, markers in outbred MF1 mice were tested for association with BMD. Three chromosome 11 SNPs were identified that were associated with BMD within the Bmd11 QTL. Finally, our approach provides strong support for Wnt9a, Rasd1, or both underlying Bmd11. Integration of multiple genetic and genomic data sets can substantially improve the efficiency of QTL fine-mapping and candidate gene identification.
Related Links	http://dx.doi.org/10.1359/jbmr.080908
Ending Page	116
Page Count	12
Starting Page	105
File Format	PDF
ISSN	08840431
e-ISSN	15234681
Journal	Journal of Bone and Mineral Research
Issue Number	1
Volume Number	24
Language	English
Publisher	Amer Soc Bone & Mineral Res.
Publisher Date	2009-01-01
Access Restriction	Open
Rights Holder	Amer Soc Bone & Mineral Res.
Subject Keyword	Endocrinology, Diabetes and Metabolism Orthopedics and Sports Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Orthopedics and Sports Medicine Endocrinology, Diabetes and Metabolism

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