NHP Exomics
Expanding whole exome resequencing into non-human primates
Background  Complete exome resequencing has the power to greatly expand our understanding of non-human primate genomes. This includes both a better appreciation of the variation that exists in non-human primate model species, but also an improved annotation of their genome. Non-human primates are lauded for their translational relevance, but this extends only as far as the underlying molecular epidemiology can take it. By developing an understanding of the variation between individuals, non-human primate models of human disease can be better developed. This effort is hindered largely by the lack of comprehensive information on specific non-human primate genetic variation and the costs of generating this data on a large scale. If the tools that have been developed in humans for complete exome resequencing can be applied to closely related non-human primate species then these difficulties can be circumvented.    Results  Using a human whole exome enrichment technique, chimpanzee and rhesus macaque samples were captured alongside a human sample and sequenced using standard next-generation methodologies. The results from the three species were then compared for efficacy. The chimpanzee sample worked as well following exome capture based on the human genome as the human sample. The rhesus macaque sample showed significant coverage (~85%) in protein-coding sequence but significantly less in untranslated regions. Both chimpanzee and rhesus macaque showed significant numbers of frameshift mutations compared to self-genomes and suggest a need for further annotation.    Conclusion  Current whole exome resequencing technologies can successfully be used to identify coding-region variation in non-human primates extending into old world monkeys. This is turn offers the opportunity to develop these species as genetic models of human disease. In addition to identifying variation, whole exome resequencing also allows for a better annotation of non-human primate genomes.