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Expanding whole exome resequencing into non-human primates.doc

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Expanding whole exome resequencing into non-human primates

VallenderGenomeBiology2011,12:R87 /2011/12/9/R87 RESEARCH OpenAccess Expandingwholeexomeresequencingintonon- humanprimates EricJVallender Abstract Background:Completeexomeresequencinghasthepowertogreatlyexpandourunderstandingofnon-human primategenomes.Thisincludesbothabetterappreciationofthevariationthatexistsinnon-humanprimate modelspecies,butalsoanimprovedannotationoftheirgenomes.Bydevelopinganunderstandingofthe variationbetweenindividuals,non-humanprimatemodelsofhumandiseasecanbebetterdeveloped.Thiseffortis hinderedlargelybythelackofcomprehensiveinformationonspecificnon-humanprimategeneticvariationand thecostsofgeneratingthesedata.Ifthetoolsthathavebeendevelopedinhumansforcompleteexome resequencingcanbeappliedtocloselyrelatednon-humanprimatespecies,thenthesedifficultiescanbe circumvented. Results:Usingahumanwholeexomeenrichmenttechnique,chimpanzeeandrhesusmacaquesampleswere capturedalongsideahumansampleandsequencedusingstandardnext-generationmethodologies.Theresults fromthethreespecieswerethencomparedforefficacy.Thechimpanzeesampleshowedsimilarcoveragelevels anddistributionsfollowingexomecapturebasedonthehumangenomeasthehumansample.Therhesus macaquesampleshowedsignificantcoverageinprotein-codingsequencebutsignificantlylessinuntranslated regions.Bothchimpanzeeandrhesusmacaqueshowedsignificantnumbersofframeshiftmutationscomparedto self-genomesandsuggestaneedforfurtherannotation. Conclusions:Currentwholeexomeresequencingtechnologiescansuccessfullybeusedtoidentifycoding-region variationinnon-humanprimatesextendingintooldworldmonkeys.Inadditiontoidentifyingvariation,whole exomeresequencingcanaidinbetterannotationofnon-humanprimategenomes. Background had beenassociated withelucidation ofpolymorphism. The role of genetic variation in establishing individual The historical importance of rodents in biomedical differencesiswell-established.HapMap[1],theHuman research coupled with the clonal nature of the strains Genome Diversity Project [2], and most recently the a