This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to systematically explore the molecular and genomic evolution of mammals focused on humans and non-human primates in order to better understand the context of human disease. First we will catalog the differences between species with a focus on regions showing evidence for positive selection or genes demonstrated to be associated with disease. This effort will make use of all major primate lineages but will in particular focus on the more commonly used biomedical model species (notably rhesus macaques and common marmosets). It will also include both differences between (divergence) and within (polymorphism) species. We will then functionally investigate the consequences of these differences, as well as the functionality of ancestral sequences, in vitro. We will also assess the effects of polymorphic variation from non-human primates ex vivo and in vivo through measurement of mRNA levels and through correlation with physiological measures. This work will elucidate if specific psychiatric disorders or symptoms are unique to humans resulting from human-specific genetic changes and the extent to which and ways that these psychiatric disorders and their treatment can be modeled in other organisms, particularly non-human primates. This will allow researchers to leverage the power of molecular evolution and comparative genetics to greater effect in studies of human disease going forward and to refine candidate gene analyses and better place into context animal models of neuropsychiatric disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-49
Application #
8172877
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2010-05-01
Project End
2011-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
49
Fiscal Year
2010
Total Cost
$18,052
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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