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Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes)

Anna V Kukekova1*, Jennifer L Johnson1, Clotilde Teiling2, Lewyn Li3, Irina N Oskina4, Anastasiya V Kharlamova4, Rimma G Gulevich4, Ravee Padte1, Michael M Dubreuil1, Anastasiya V Vladimirova4, Darya V Shepeleva4, Svetlana G Shikhevich4, Qi Sun5, Lalit Ponnala5, Svetlana V Temnykh1, Lyudmila N Trut4 and Gregory M Acland1

  • * Corresponding author: Anna V Kukekova

  • † Equal contributors

Author Affiliations

1 Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853, USA

2 Roche Diagnostics, Indianapolis, IN 46256, USA

3 454 Life Sciences, Branford, CT 06405, USA

4 Institute of Cytology and Genetics of the Russian Academy of Sciences, Novosibirsk, 630090, Russia

5 Computational Biology Service Unit, Biotechnology Center, Cornell University, Ithaca, NY 14853, USA

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BMC Genomics 2011, 12:482  doi:10.1186/1471-2164-12-482

Published: 3 October 2011



Two strains of the silver fox (Vulpes vulpes), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed.


cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence). Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p < 0.05) was observed for 335 genes, fewer than 3% of the total number of genes identified in the fox transcriptome.


Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information.