Genetics of devil facial tumour disease

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Genetics of devil facial tumour disease

• Kathy Belov
• Faculty of Veterinary Science
• University of Sydney

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Tasmanian devils
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Tasmanian devils

• Worlds largest remaining marsupial carnivore
• Extinct on mainland 600 years ago
• Restricted to Tasmania
• Unexplained population crashes in 1850s, 1900s
  and 1940s

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Devil facial tumour disease

• 150,000 50,000 in past 10 years
• Extinct within 25 years

Photo Hannah Bender
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• Emerged in NE in 1996
• Local declines 90
• Restricted to devils

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Devil Facial Tumour Disease

• Infectious direct contact req
• Incubation period not known
• No diagnostic test
• Once lesions appear always fatal
• No evidence of recovery or natural immunity

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Tasmanian devil facial tumour disease
Pearse Swift (2006) Nature, 439549
Microsatellite typing confirms that the tumour is
an allograft
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Allograft theory The tumour cell is the
infectious agent
Spread by biting
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Why is this foreign cell not rejected by the
immune system?
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Graft rejection

• Tumour graft
• The cause of transplant rejection is recognition
  of foreign MHC molecules on the cell surface
• Donor and recipient MHC matched

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The Major Histocompatibility Complex

• Key region of genome involved in response against
• Infectious disease
• Parasites
• Autoimmunity
• Graft rejection

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MHC diversity and self/non-self recognition
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Genetic diversity in devils

• Why are DFTD cells not recognized by the immune
  system?
• Is the MHC type of the tumour the same as the MHC
  type of the host?
• How different are MHC types of different devils?

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Measuring MHC diversity with mixed lymphocyte
responses
Responder
Stimulator (labeled)
MHC-alike No proliferation No 3H incorporation
MHC-disparate Proliferation 3H incorporation
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Measuring MHC diversity
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MHC Diversity

• MHC Genotyping
• The tumours are all identical
• Overall diversity at MHC is very low

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MHC diversity is critically low.Devils share
the same MHC type as the tumour.Devils do not
recognize tumour cells as foreign and do not
mount an immune response.
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First link between loss of genetic diversity and
emergence of disease in wild
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MHC diversity new types
A D D D A 1 1 1 1 1
1 1 A 1 1 A
L L D A H I D M L M D I
D H L G M B
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MHC diversity
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Are MHC-disparate animals resistant to DFTD??
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Do MHC-disparate individuals recognize the tumour
as non-self?

• Cedric (MHC disparate - L) and Clinky (MHC
  similar to DFTD - A)
• Vaccinated with killed cells
• Transmission experiment

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Evolution of DFTD
Anne-Maree Pearse
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Implications of DFTD evolution

• Are DFTD strains functionally different?
• Evolve to be less aggressive?
• Evolve immune evasion strategies?

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Captive breeding the insurance population
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MHC Diversity in Insurance Popn
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115 animals in 8 zoos 34 young 2008
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