Increasingly, human neurological diseases are being mapped to genome regions shared between affected individuals, however current methods generally identify large genomic regions containing many genes. For example, Williams-Beuren Syndrome (WBS), results in learning deficits and cardiopulmonary phenotypes and is associated with deletion of at least 25 genes in the 1.5 Mb WBS critical region (WBSCR). Interestingly, those affected with WBS often have a 'hyper-gregarious'nature and enhanced language or music skills. Despite the small number of genes implicated, the lack of a social animal model has limited the study of how WBSCR genes affect social interaction and little is known about the WBSCR genes or how they contribute to the characteristic WBS symptoms. Social insects, including ants and bees, are a tractable experimental system to test the in vivo effects of WBSCR genes on complex social behaviors. We propose to perturb the expression level of genes from the WBSCR in the social insect, Linepithema humile (Argentine ant). We will: 1) Use comparative genomics to identify WBSCR gene orthologs in several genomes and annotate their exons, regulatory elements, and repeats. 2) Develop L. humile cDNA and fosmid resources to clone, sequence, and assess the methylation state of WBSCR gene regions. 3) Use RNA interference constructs to perturb expression of WBSCR genes in ants and observe changes in individual and group behaviors. In addition to these research objectives, the principal investigator will pursue the following developmental goals with the guidance of his mentor, Dr. Gary Karpen 4) establish an independent research group 5) enhance personal mentoring and teaching skills 6) improve the quality of research. Relevance to Public Health: Social interaction is a complex behavior that profoundly affects human health and well-being. Experimentation with behavior genes in humans is not feasible, making the development of a 'social behavior'animal model system desirable. The proposed studies will elucidate the conserved protein, cis-DNA regulatory features, and gene networks involved in Williams-Beuren Syndrome and will develop a social animal model system to test other gene-behavior interactions. This study of WBSCR genes promises to identify novel biomarkers and gene targets for therapeutic intervention of behavioral disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Pilot Research Project (SC2)
Project #
5SC2MH086071-03
Application #
7911757
Study Section
Special Emphasis Panel (ZGM1-MBRS-2 (MV))
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2008-09-16
Project End
2012-01-31
Budget Start
2010-08-01
Budget End
2012-01-31
Support Year
3
Fiscal Year
2010
Total Cost
$115,125
Indirect Cost
Name
San Francisco State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
942514985
City
San Francisco
State
CA
Country
United States
Zip Code
94132
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Smith, Christopher D; Zimin, Aleksey; Holt, Carson et al. (2011) Draft genome of the globally widespread and invasive Argentine ant (Linepithema humile). Proc Natl Acad Sci U S A 108:5673-8
Smith, Christopher D; Smith, Christopher R; Mueller, Ulrich et al. (2010) Ant genomics: strength and diversity in numbers. Mol Ecol 19:31-5