The overall goal of this proposal is to discover gene-linked SNPs in rhesus macaques (Macaca mulatta) and to make these SNPs easily accessible to the non-human primate research community. We will focus on identifying SNPs associated with genes of research interest anticipating that these SNPs will be of great use to NHP investigators pursuing candidate gene association studies. This work will result in marker loci being identified in 10,000 rhesus macaque genes, and will be the first large-scale effort to identify gene-based makers in non-human primates. There will be two specific aims.
In Specific Aim 1, we will discover SNPs in the 3'end region of rhesus macaque genes.
In Specific Aim 2, we will create a publicly accessible rhesus macaque SNP database. SNPs may be found in many regions of the genome. However, SNPs in intergenic regions are of limited utility for candidate gene approaches. SNPs in coding regions are of immediate use, if found, but are relatively rare. SNPs in, or in close proximity to, the 3'end of genes can be found in rhesus macaques at high frequency. In addition, some of these SNPs have been found to have functional significance. Thus, our approach has the following advantages: 1. Efficient discovery of many SNPs;2. Identifying SNPs in genes;3. The potential to discover functional SNPs. We have identified over 6,000 primer pairs that have been used to amplify the 3'region of rhesus macaque genes and will have identified over 10,000 such primer pairs by the end of the original proposal. We will develop and deploy a Web accessible data portal allowing access to all rhesus macaque SNPs in the NCBI dbSNP database. This portal and accompanying tool set will facilitate access to rhesus macaque SNP information, including SNP identity, position, population specificity and allele frequency. It will also provide users with basic tools to analyze SNP genotypes between and within Indian and Chinese rhesus populations. The targeted approach to obtaining SNPs contained within genes, will provide the rhesus macaque research community with a comprehensive set of SNPs linked to specific genes to advance the genetic analysis of complex traits. The gene-based SNPs we discover will advance translational research the areas of: SIV/HIV biology, alcoholism, stress/anxiety, neurodegenerative diseases, macular degeneration, stem cell biology, reproductive dysfunction and diabetes.
