Nonhuman primates offer a unique model for studying human biology, disease, and evolution. Nevertheless, 95% of nonhuman primates lack the basic genomic sequence resources required for modern genetic and comparative genetic studies of disease, including AIDS. Thus, there is a need to develop affordable and efficient methods that use the available nonhuman primate genomic resources as a springboard for population- based genomic sequencing in a greater diversity of species. The focus of this R21 proposal is to test and to demonstrate the capability of a newly developed genomic technology, microarray-based genomic selection (MGS), as such a method. We and others have shown that microarrays can be used to selectively enrich for targeted regions of a complex genome from total genomic DNA, thereby providing the templates necessary for population-based resequencing of the targeted intervals. However, if MGS could be used in a cross-species format, its utility would increase exponentially. Though the cross-species application of MGS is untested, analogous studies of cross-species hybridization between nonhuman primates using gene expression microarrays have already proved successful. The first goal of this proposal is therefore to determine the capability of cross-species MGS to enrich for orthologous targeted genomic regions of nonhuman primates at divergence levels from 1-10% (Aim 1). The second goal of this proposal is to directly demonstrate the utility of cross-species MGS for nonhuman primate and AIDS research. To do so we will apply the cross-species MGS approach toward sequencing 125-250 candidate genes for the benign nature of SIV infection in the sooty mangabey, an exceptional nonhuman primate model for AIDS research that lacks genomic resources (Aim 2). In summary, a method that can simultaneously produce both comparative and population-based sequence data from targeted regions in multiple species will be tested and applied toward the identification of genetic factors that suppress progression to AIDS.
As our closest living relatives, nonhuman primates are a unique genetic resource for studying disease progression to AIDS. The goal of this research project is to apply a new DNA sequencing technology toward sequencing genes in nonhuman primates, including a biomedical model for AIDS research.
