Fawcett et al. BMC Genomics 2011, 12:311 http://www.biomedcentral.com/1471-2164/12/311 R E S E A R C H A R T I C L E Open Access Characterization of single-nucleotide variation in Indian-origin rhesus macaques (Macaca mulatta) Gloria L Fawcett1,2, Muthuswamy Raveendran1, David Rio Deiros1, David Chen1, Fuli Yu1,2, Ronald Alan Harris2, Yanru Ren1, Donna M Muzny1,2, Jeffrey G Reid1,2, David A Wheeler1,2, Kimberly C Worley1,2, Steven E Shelton4, Ned H Kalin4,5, Aleksandar Milosavljevic2, Richard Gibbs1,2 and Jeffrey Rogers1,2,3* Abstract Background: Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies. Results: We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease. Conclusions: Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs, providing new opportunities to identify rhesus models for human disease. Keywords: single nucleotide polymorphism, common variants, SOLiD™, genetic variation, rhesus macaque Background Experimental study of rhesus macaques (Macaca mulatta) is critical to progress in many aspects of bio- medical research. This species is widely used in neuro- biology and behavioral science [1-5], endocrinology [6,7], physiological studies of cardiovascular disease and obesity [8], diabetes [9], alcoholism and addiction research [10,11], and other diverse fields [12,13]. Rhesus macaques are central to progress in the development of * Correspondence: jr13@bcm.edu 1Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA Full list of author information is available at the end of the article vaccines and anti-viral therapies against HIV infection and AIDS because these animals are the best available animal model for studies of lentivirus infection [14,15]. However, despite the wide use of rhesus macaques in research, this species is under-utilized as a model organ- ism for investigation of genetic processes influencing human biology and human disease. One factor limiting the use of rhesus monkeys in genetic analyses is the lack of existing information about intra-species poly- morphism. Currently, dbSNP contains fewer than 900 validated SNPs for this species (http://www.ncbi.nlm.nih. gov/projects/SNP/) [16] and only a small number of copy number variants (CNVs) have been described © 2011 Fawcett et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.