Download - Tsetse fly
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Combining the tsetse fly genome with
disease control
Lessons from triatomine bugs: Chagas disease
control
SNP diversity
Cool phylogenomics
Tsetse fly
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Sympatric speciation
Vector-borne transmission in Vector-borne transmission in Trypanosoma cruziTrypanosoma cruzi
Triatomine bugs (Rhodnius sp.)Palms
Triatomines evolved with the formation of South America 95 MYA*
* Gaunt and Miles (2002) reviewed by Science
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Sylvatic hosts of Sylvatic hosts of T. cruziT. cruzi
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Basis of the Southern cone initiative:
Triatoma infestans - a key vector in Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay and southern Peru
- Domiciliated (domesticated)
- Susceptible to insecticide (adults and nymphs)
- Insecticide control is cheap
A domesticated vector has A domesticated vector has nowhere to hidenowhere to hide
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Many deaths resulting from a genetically isolated Many deaths resulting from a genetically isolated vector populationvector population
A simple solution…….A simple solution…….Chris Schofield
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Apparent distribution of Triatoma infestans
1982 2002
The success of targeted vector control
Chris Schofield
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Control InitiativesObjectives
2. Interrupt vectorial transmission
1. Interrupt transfusional transmission
The Southern Cone ProjectThe Southern Cone Project
Chris Schofield
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??
PATTEC Lake Victoria Basin Initiative
The Tsetse BeltThe Tsetse Belt
TanzaniaTanzania
KenyaKenya
UgandaUganda
The problem
Not a continuous inter-breeding population but distribution of
specie and sub-species populations
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What might the tsetse genome look like?
• EST clustering pipelines from the current tsetse library databases (midgut, salivary gland, and fatbody)
• Identified one SNP every 654 base pairs (Pi = 0.0015)
• The mosquito genome gives 1 SNP every 785 bp for cds (Pi = 0.0013) and 1/627 overall
• Far higher than in Drosophila
SNP diversity
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Experimental criticisms• EST SNP diversity doesn’t equate to the
total SNP diversity of genomic coding sequences– Controls are needed
• However we should not be surprised if SNP diversity was as high as in Anopheles - biogeographically there are strong similarities
High levels of heterozygosity would create annotation problems
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What can a genome do?
Recipe:
• A) Take one draft genome
• B) Add a bioinformatics pipeline to – B1) identify small tandem repeats– B2) Design primers for each tandem repeat
• C) Apply genome-scale microsatellite loci to field samples
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Microsatellites
• 70 loci spanning 2Mb of T. cruzi genome.• Resolution of population genetic structure of T. cruzi lineages
in principal host species.• Hardy-Weinberg recombination analysis
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Brazil: opossum Philander, Didelphis and monkey
Bolivia: opossum Philander and Didelphis
Venezuela: opossum Didelphis
AALLLLOOPPAARRYY
VVIICCAARRIIAANNCCEEIsolation
not bypure
geo-graphicdistance
Biogeographic Biogeographic markersmarkers
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Sympatry and TCIIc
Between speciesBetween species
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Sympatry and TCISympatry and TCI
Geneflow
Within speciesWithin species
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The State of PlayThe State of Play
• 1 X draft genome next year
• Funding in place to stripe out the MSATs (NBN)
• Some MSATs defined• Evidence of genetic
allopatry
• Leverhulme network of Chris Schofield coordinates the PATTEC Lake Victoria Basin projects in Kenya, Uganda and Tanzania
• Kenyan and Ugandan governments have taken development loans to control tsetse
Community ecology
Genetics
Governments
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Combining public health & pop. gen.
• Kenyan and Ugandan government
• Population collections Schofield network– Kenya,– Uganda
– (Tanzania)
Morphometrics
MSATs
PATTEC
Proposed strategy
Targeted tsetse control
African development loans
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In summaryIn summary• Fly collections are completed• Genome is poised - could be a heterozygosity
issue• Governments are interested and monies are
available• Good geneticists in Kenya, Uganda and
Tanzania• Combine a high throughput, low cost technology
(morphometrics) with MSATs - standardize the method …. then we have ignition
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Acknowledgements• Win Hide, SANBI, SAWin Hide, SANBI, SA• Chris Schofield, LSHTM, UKChris Schofield, LSHTM, UK• Mark Walmawa (SANBI pending)Mark Walmawa (SANBI pending)• Christopher Maher & Lincoln Stein
(Cold Spring Harbour, US)
• Johnson Omur (BTRC, Kenya)Johnson Omur (BTRC, Kenya)• Dan Masiga (ICIPE, Kenya)Dan Masiga (ICIPE, Kenya)
Funding from the Wellcome Trust, NBN, SA and RCUK fellowship to MWG
• Michael Miles, LSHTM• Martin Llewellyn, LSHTM
Tsetse fly
Chagas disease