| Summary: | <p>Abstract</p> <p>Background</p> <p>Certain mutations in the vitamin K epoxide reductase subcomponent 1 gene (<it>vkorc1</it>) mediate rodent resistance to warfarin and other anticoagulants. Testing for resistance often involves analysis of the <it>vkorc1</it>. However, a genetic test for the roof rat (<it>Rattus rattus</it>) has yet to be developed. Moreover, an available roof rat <it>vkorc1 </it>sequence would enable species identification based on <it>vkorc1 </it>sequence and the evaluation of natural selection on particular <it>vkorc1 </it>polymorphisms in the Norway rat (<it>R. norvegicus</it>).</p> <p>Results</p> <p>We report the coding sequence, introns and 5' and 3' termini for the <it>vkorc1 </it>gene of roof rats (<it>R. r. alexandrinus </it>and <it>R. r. frugivorus</it>) from Uganda, Africa. Newly designed PCR primers now enable genetic testing of the roof rat and Norway rat. Only synonymous and noncoding polymorphisms were found in roof rats from Uganda. Both nominal subspecies of roof rats were indistinguishable from each other but were distinct from <it>R. losea </it>and <it>R. flavipectus</it>; however, the roof rat also shares at least three coding sequence polymorphisms with <it>R. losea </it>and <it>R. flavipectus</it>. Many of recently published <it>vkorc1 </it>synonymous and non-synonymous single nucleotide polymorphisms (SNPs) in Norway rats are likely SNPs from roof rats and/or other <it>Rattus </it>species. Tests applied to presumably genuine Norway rat <it>vkorc1 </it>SNPs are consistent with a role for selection in two populations carrying the derived Phe63Cys and Tyr139Cys mutations.</p> <p>Conclusion</p> <p>Geographic mapping of <it>vkorc1 </it>SNPs in roof rats should be facilitated by our report. Our assay should be applicable to most species of <it>Rattus</it>, which are intermediate in genetic distance from roof and Norway rats. <it>Vkorc1</it>-mediated resistance due to non-synonymous coding SNPs is not segregating in roof rats from Uganda. By using the roof rat sequence as a reference <it>vkorc1</it>, SNPs now can be assigned to the correct rat species with more confidence. Sampling designs and genotyping strategies employed so far have helped detect candidate mutations underlying <it>vkorc1</it>-mediated resistance, but generally provided unsuitable data to test for selection. We propose that our understanding of <it>vkorc1</it>-mediated evolution of resistance in rodents would benefit from the adoption of sampling and genotyping designs that enable tests for selection on <it>vkorc1</it>.</p>
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