Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC

Yuanyuan Cheng, Andrew Stuart, Katrina Morris, Robyn Taylor, Hannah Siddle, Janine Deakin, Menna Jones, Chris Amemiya, Katherine Belov

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 aplotypes 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.
Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalBMC Genomics
Volume13:87
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Gene Dosage
Major Histocompatibility Complex
Antigens
Marsupialia
Pseudogenes
Haplotypes
MHC Class I Genes
Neoplasms
MHC Class II Genes
Disease Susceptibility
Tumor Cell Line
Genes
Allografts
Chromosomes
Population

Cite this

Cheng, Yuanyuan ; Stuart, Andrew ; Morris, Katrina ; Taylor, Robyn ; Siddle, Hannah ; Deakin, Janine ; Jones, Menna ; Amemiya, Chris ; Belov, Katherine. / Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC. In: BMC Genomics. 2012 ; Vol. 13:87. pp. 1-13.
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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 aplotypes 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.",
keywords = "MHC, Tasmanian devil, Copy number variation, Devil facial tumour disease.",
author = "Yuanyuan Cheng and Andrew Stuart and Katrina Morris and Robyn Taylor and Hannah Siddle and Janine Deakin and Menna Jones and Chris Amemiya and Katherine Belov",
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Cheng, Y, Stuart, A, Morris, K, Taylor, R, Siddle, H, Deakin, J, Jones, M, Amemiya, C & Belov, K 2012, 'Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC', BMC Genomics, vol. 13:87, pp. 1-13. https://doi.org/10.1186/1471-2164-13-87

Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC. / Cheng, Yuanyuan; Stuart, Andrew; Morris, Katrina; Taylor, Robyn; Siddle, Hannah; Deakin, Janine; Jones, Menna; Amemiya, Chris; Belov, Katherine.

In: BMC Genomics, Vol. 13:87, 2012, p. 1-13.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC

AU - Cheng, Yuanyuan

AU - Stuart, Andrew

AU - Morris, Katrina

AU - Taylor, Robyn

AU - Siddle, Hannah

AU - Deakin, Janine

AU - Jones, Menna

AU - Amemiya, Chris

AU - Belov, Katherine

PY - 2012

Y1 - 2012

N2 - 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 aplotypes 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.

AB - 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 aplotypes 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.

KW - MHC

KW - Tasmanian devil

KW - Copy number variation

KW - Devil facial tumour disease.

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DO - 10.1186/1471-2164-13-87

M3 - Article

VL - 13:87

SP - 1

EP - 13

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

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