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Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial


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Siddle, HV, Kreiss, A, Eldridge, MDB, Noonan, E, Clarke, CJ, Pyecroft, SB, Woods, GM and Belov, K 2007 , 'Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial' , National Academy of Sciences Proceedings, vol. 104, no. 41 , pp. 16221-16226 , doi: 10.1073/pnas.0704580104.

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A fatal transmissible tumor spread between individuals by biting
has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous
marsupial. Here we provide genetic evidence establishing
that the tumor is clonal and therefore foreign to host devils. Thus,
the disease is highly unusual because it is not just a tumor but also
a tissue graft, passed between individuals without invoking an
immune response. The MHC plays a key role in immune responses
to both tumors and grafts. The most common mechanism of
immune evasion by tumors is down-regulation of classical cell
surface MHC molecules. Here we show that this mode of immune
escape does not occur. However, because the tumor is a graft, it
should still be recognized and rejected by the host’s immune
system due to foreign cell surface antigens. Mixed lymphocyte
responses showed a lack of alloreactivity between lymphocytes of
different individuals in the affected population, indicating a paucity
of MHC diversity. This result was verified by genotyping,
providing a conclusive link between a loss of MHC diversity and
spread of a disease through a wild population. This novel disease
arose as a direct result of loss of genetic diversity and the aggressive
behavior of the host species. The neoplastic clone continues to
spread although the population, and, without active disease control
by removal of affected animals and the isolation of diseasefree
animals, the Tasmanian devil faces extinction.

Item Type: Article
Authors/Creators:Siddle, HV and Kreiss, A and Eldridge, MDB and Noonan, E and Clarke, CJ and Pyecroft, SB and Woods, GM and Belov, K
Keywords: conservation genetics Tasmanian devil wildlife disease immune evasion
Journal or Publication Title: National Academy of Sciences Proceedings
ISSN: 0027-8424
DOI / ID Number: 10.1073/pnas.0704580104
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