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Tsetse fly. 2. 1. Lessons from triatomine bugs: Chagas disease control. SNP diversity. 3. Combining the tsetse fly genome with disease control. Cool phylogenomics. Michael Gaunt LSHTM/ SANBI. Vector-borne transmission in Trypanosoma cruzi. Sympatric speciation.
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Tsetse fly 2 1 Lessons from triatomine bugs: Chagas disease control SNP diversity 3 Combining the tsetse fly genome with disease control Cool phylogenomics Michael Gaunt LSHTM/ SANBI
Vector-borne transmission in Trypanosoma cruzi Sympatric speciation Triatomines evolved with the formation of South America 95 MYA* Triatomine bugs (Rhodnius sp.) Palms * Gaunt and Miles (2002) reviewed by Science
A domesticated vector has nowhere to hide 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
Many deaths resulting from a genetically isolated vector population A simple solution……. Chris Schofield
The success of targeted vector control Apparent distribution of Triatoma infestans 2002 1982 Chris Schofield
Control Initiatives The Southern Cone Project Objectives 1. Interrupt transfusional transmission 2. Interrupt vectorial transmission Chris Schofield
The problem The Tsetse Belt Kenya Not a continuous inter-breeding population but distribution of specie and sub-species populations Uganda ?? Tanzania PATTEC Lake Victoria Basin Projects LTTRN - Leverhulme Trust Tsetse Research Network
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 estimate GACTGATAGACTGATAT----------------------------------GACTGATACACTGATAT-----------------GACTGATAGACTGATATGACTGATACACTGATAT GACTGATAGACTGATAT-----------------GACTGATAGACTGATAT8bp * 8bp STACKPack D2_cluster 6 out of 10 traces Must be present
High levels of heterozygosity would create annotation problems 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
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
Bolivia: opossum Philander and Didelphis Biogeographic markers V I C A R I A N C E A L L O P A R Y Brazil: opossum Philander,Didelphis andmonkey Venezuela: opossum Didelphis Isolation not by pure geo-graphic distance
Between species Sympatry and TCIIc
Within species Sympatry and TCI Geneflow
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 The State of Play Community ecology Genetics PATTEC Governments • Kenyan and Ugandan governments have taken development loans to control tsetse
Kenyan and Ugandan government Population collections Schofield network Kenya Uganda (Tanzania) Combining public health & pop. gen. PATTEC Morphometrics Proposed strategy MSATs African development loans Targeted tsetse control
In summary T. cruzi and triatomine model are real examples of how thinking big population thinking solves problems • 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 Goal
Acknowledgements • Win Hide, SANBI, SA • Chris Schofield, LSHTM, UK • Mark Walmawa (SANBI pending) • Christopher Maher & Lincoln Stein (Cold Spring Harbour, US) • Johnson Omur (BTRC, Kenya) • Dan Masiga (ICIPE, Kenya) Tsetse fly • Michael Miles, LSHTM • Martin Llewellyn, LSHTM Chagas disease Funding from the Wellcome Trust, NBN, SA and RCUK fellowship to MWG