The completion of the genome sequence brings us several major advantages that we can use in positional cloning. First of all, all of the coding sequences of a chromosomal region of interest can be identified. Secondly, information on the introns, 5' and 3' region of the sequences will be available, making it possible for the gene to be analyzed thoroughly throughout the coding region and the regulatory region. Thirdly, with the availability of all the sequences of a chromosomal region, nucleotide organization, gene ordering, gene expression patterns, and chromosomal structure can be analyzed. At the same time, high throughput technologies for mutation analysis and gene profiling have also developed rapidly to meet the new needs. All of these developments will greatly improve our search for candidate genes in positional cloning. By using a new strategy which combines genetic mapping, genome resources, and high throughput technology, we have identified mutated genes from two spontaneous mutation models in the last ten months. Our work suggests that positional cloning is no longer years of team effort of several laboratories for identifying one gene, but it is a work of one laboratory in one year for several genes. In this extraordinary study, we propose the massive screening of the targeted spontaneous mutants in JAX. In the four years of this project, we will focus on mouse models for skeletal diseases and expect to identify mutated genes from more than 10 spontaneous mutations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR051190-03
Application #
7046962
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Sharrock, William J
Project Start
2004-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
3
Fiscal Year
2006
Total Cost
$279,914
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Orthopedics
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Cao, Yanhong; Wang, Lishi; Wang, Cong-Yi et al. (2018) Sex Differences in Correlation with Gene Expression Levels between Ifi200 Family Genes and Four Sets of Immune Disease-Relevant Genes. J Immunol Res 2018:1290814
Wang, Lishi; Jiao, Yan; Sun, Shuqiu et al. (2015) Gene network of a phosphoglycerate mutase in muscle wasting in mice. Cell Biol Int 39:666-77
Zhang, Yueying; Huang, Jinsong; Jiao, Yan et al. (2015) Bone morphology in 46 BXD recombinant inbred strains and femur-tibia correlation. ScientificWorldJournal 2015:728278
Deng, Nan; Jiao, Yan; Cao, Yanhong et al. (2014) Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA. BMC Immunol 15:57
Huang, Yue; Zhu, Xiaodong; Wang, Lishi et al. (2014) Genome wide analysis of sex difference in gene expression profiles of bone formations using sfx mice and BXD RI strains. ScientificWorldJournal 2014:584910
Wei, Wei; Jiao, Yan; Ma, Yonghui et al. (2014) Effect of fluorosis on liver cells of VC deficient and wild type mice. ScientificWorldJournal 2014:287464
Wang, Lishi; Lu, Wenli; Zhang, Lei et al. (2014) Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men. PLoS One 9:e84485
Yan, Jian; Jiao, Yan; Chen, Hong et al. (2013) Dual effects of IL-1 overactivity on the immune system in a mouse model of arthritis due to deficiency of IL-1 receptor antagonist. J Genet Genomics 40:83-91
Cao, Yanhong; Huang, Yue; Wang, Lishi et al. (2013) Different coexpressions of arthritis-relevant genes between different body organs and different brain regions in the normal mouse population. Gene 515:396-402
Huang, Y; Wang, L; Bennett, B et al. (2013) Potential role of Atp5g3 in epigenetic regulation of alcohol preference or obesity from a mouse genomic perspective. Genet Mol Res 12:3662-74

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