Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC
Cheng, Y and Stuart, A and Morris, K and Taylor, R and Siddle, HV and Deakin, JE and Jones, M and Amemiya, CT and Belov, K, Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC, BMC Genomics, 13, (1) Article 87. ISSN 1471-2164 (2012) [Refereed Article]
The Tasmanian devil (Sarcophilus harrisii) is currently under threat of extinction due to an
unusual fatal contagious cancer called Devil Facial Tumour Disease (DFTD). DFTD is
caused by a clonal tumour cell line that is transmitted between unrelated individuals as an
allograft without triggering immune rejection due to low levels of Major Histocompatibility
Complex (MHC) diversity in Tasmanian devils.
Here we report the characterization of the genomic regions encompassing MHC Class I and
Class II genes in the Tasmanian devil. Four genomic regions approximately 960 kb in length
were assembled and annotated using BAC contigs and physically mapped to devil
Chromosome 4q. 34 genes and pseudogenes were identified, including five Class I and four
Class II loci. Interestingly, when two haplotypes from two individuals were compared, three
genomic copy number variants with sizes ranging from 1.6 to 17 kb were observed within the
classical Class I gene region. One deletion is particularly important as it turns a Class Ia gene
into a pseudogene in one of the haplotypes. This deletion explains the previously observed
variation in the Class I allelic number between individuals. The frequency of this deletion is
highest in the northwestern devil population and lowest in southeastern areas.
The third sequenced marsupial MHC provides insights into the evolution of this dynamic
genomic region among the diverse marsupial species. The two sequenced devil MHC
haplotypes revealed three copy number variations that are likely to significantly affect
immune response and suggest that future work should focus on the role of copy number
variations in disease susceptibility in this species.