Systems Genetics Analysis of Mouse Chondrocyte Differentiation

One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression prof...

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Main Authors: Suwanwela, Jaijam, Farber, Charles R, Haung, Bau-lin, Song, Buer, Pan, Calvin, Lyons, Karen M, Lusis, Aldons J
Format: Online
Language:English
Published: Wiley Subscription Services, Inc., A Wiley Company 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179327/
id pubmed-3179327
recordtype oai_dc
spelling pubmed-31793272012-04-01 Systems Genetics Analysis of Mouse Chondrocyte Differentiation Suwanwela, Jaijam Farber, Charles R Haung, Bau-lin Song, Buer Pan, Calvin Lyons, Karen M Lusis, Aldons J Original Article One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research. Wiley Subscription Services, Inc., A Wiley Company 2011-04 2010-10-14 /pmc/articles/PMC3179327/ /pubmed/20954177 http://dx.doi.org/10.1002/jbmr.271 Text en Copyright © 2011 American Society for Bone and Mineral Research http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Suwanwela, Jaijam
Farber, Charles R
Haung, Bau-lin
Song, Buer
Pan, Calvin
Lyons, Karen M
Lusis, Aldons J
spellingShingle Suwanwela, Jaijam
Farber, Charles R
Haung, Bau-lin
Song, Buer
Pan, Calvin
Lyons, Karen M
Lusis, Aldons J
Systems Genetics Analysis of Mouse Chondrocyte Differentiation
author_facet Suwanwela, Jaijam
Farber, Charles R
Haung, Bau-lin
Song, Buer
Pan, Calvin
Lyons, Karen M
Lusis, Aldons J
author_sort Suwanwela, Jaijam
title Systems Genetics Analysis of Mouse Chondrocyte Differentiation
title_short Systems Genetics Analysis of Mouse Chondrocyte Differentiation
title_full Systems Genetics Analysis of Mouse Chondrocyte Differentiation
title_fullStr Systems Genetics Analysis of Mouse Chondrocyte Differentiation
title_full_unstemmed Systems Genetics Analysis of Mouse Chondrocyte Differentiation
title_sort systems genetics analysis of mouse chondrocyte differentiation
description One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research.
publisher Wiley Subscription Services, Inc., A Wiley Company
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179327/
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