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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
1 2
3
Michael GauntLSHTM/ SANBI
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
Sylvatic hosts of Sylvatic hosts of T. cruziT. cruzi
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
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
Apparent distribution of Triatoma infestans
1982 2002
The success of targeted vector control
Chris Schofield
Control InitiativesObjectives
2. Interrupt vectorial transmission
1. Interrupt transfusional transmission
The Southern Cone ProjectThe Southern Cone Project
Chris Schofield
??
PATTEC Lake Victoria Basin Projects LTTRN - Leverhulme Trust Tsetse Research Network
The Tsetse BeltThe Tsetse Belt
TanzaniaTanzania
KenyaKenya
UgandaUganda
The problem
Not a continuous inter-breeding population but distribution of
specie and sub-species populations
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 518 base pairs (Pi = 0.0019)
• 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
A very conservative estimateA very conservative estimateGACTGATAGACTGATAGGACTGATATACTGATAT--------------------------------------------------------------------GACTGATAGACTGATACCACTGATATACTGATAT----------------------------------GACTGATAGACTGATAGGACTGATATACTGATATGACTGATAGACTGATACCACTGATAT ACTGATAT GACTGATAGACTGATAGGACTGATATACTGATAT----------------------------------GACTGATAGACTGATAGGACTGATATACTGATAT
8bp8bp * * 8bp8bp
6 out of 10 traces
Must be present
STACKPackD2_cluster
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
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
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
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
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
PATTEC
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
In summaryIn summary
• Fly collections are completed• Genome is poised - could be a heterozygosity
issue• Good geneticists in Kenya, Uganda and
Tanzania• Combine a high throughput, low cost technology
(morphometrics) with MSATs - standardize the method …. then we have ignition
• Governments are interested and monies are available
T. cruzi and triatomine model are real examples of how thinking big population thinking solves problems
Goal
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