title: Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Andrew
authors.initials: A
authors.lastname: Stuart
authors.forename: Katrina
authors.initials: K
authors.lastname: Morris
authors.forename: Robyn
authors.initials: R
authors.lastname: Taylor
authors.forename: Hannah
authors.initials: H
authors.lastname: Siddle
authors.forename: Janine
authors.initials: J
authors.lastname: Deakin
authors.forename: Menna
authors.initials: M
authors.lastname: Jones
authors.forename: Chris T
authors.initials: CT
authors.lastname: Amemiya
authors.forename: Katherine
authors.initials: K
authors.lastname: Belov
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D019143:Evolution, Molecular; D005805:Genes, MHC Class I / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D016678:Genome; D006239:Haplotypes; D008394:Marsupialia / Q000145:classification / Q000235:genetics; D010802:Phylogeny; D011544:Pseudogenes
chemical_list: D000941:Antigens