![Page 1: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/1.jpg)
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
![Page 2: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/2.jpg)
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
![Page 3: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/3.jpg)
Sylvatic hosts of Sylvatic hosts of T. cruziT. cruzi
![Page 4: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/4.jpg)
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
![Page 5: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/5.jpg)
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
![Page 6: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/6.jpg)
Apparent distribution of Triatoma infestans
1982 2002
The success of targeted vector control
Chris Schofield
![Page 7: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/7.jpg)
Control InitiativesObjectives
2. Interrupt vectorial transmission
1. Interrupt transfusional transmission
The Southern Cone ProjectThe Southern Cone Project
Chris Schofield
![Page 8: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/8.jpg)
??
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
![Page 9: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/9.jpg)
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
![Page 10: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/10.jpg)
A very conservative estimateA very conservative estimateGACTGATAGACTGATAGGACTGATATACTGATAT--------------------------------------------------------------------GACTGATAGACTGATACCACTGATATACTGATAT----------------------------------GACTGATAGACTGATAGGACTGATATACTGATATGACTGATAGACTGATACCACTGATAT ACTGATAT GACTGATAGACTGATAGGACTGATATACTGATAT----------------------------------GACTGATAGACTGATAGGACTGATATACTGATAT
8bp8bp * * 8bp8bp
6 out of 10 traces
Must be present
STACKPackD2_cluster
![Page 11: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/11.jpg)
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
![Page 12: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/12.jpg)
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
![Page 13: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/13.jpg)
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
![Page 14: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/14.jpg)
Brazil: opossum Philander, Didelphis and monkey
Bolivia: opossum Philander and Didelphis
Venezuela: opossum Didelphis
AALLLLOOPPAARRYY
VVIICCAARRIIAANNCCEEIsolation
not bypure
geo-graphicdistance
Biogeographic Biogeographic markersmarkers
![Page 15: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/15.jpg)
#
######
###########
#
#
#
#
#
#
######
###########
#
#
#
#
#
####
#####
Sympatry and TCIIc
Between speciesBetween species
![Page 16: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/16.jpg)
####
##########
###
#######
#
##############
#
#
###
######
##
#
#
#########
#####
#####
#
##
###################
#################################################################
##################################
#####
#
#
##
#
#################
#### ####
##################################
######
##########
######
###
#######
# ##########
###############################
#
###
###
#
#
#
##
####
##### #############
######
## ######################
#
######
######
########
#
####
#
###########
##
##
#
#####################################
###
#
###
#
#
##
#
##################################################
#
###
##############
#######
#########
##
# #
###########################################
##
#
Sympatry and TCISympatry and TCI
Geneflow
Within speciesWithin species
![Page 17: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/17.jpg)
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
![Page 18: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/18.jpg)
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
![Page 19: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/19.jpg)
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
![Page 20: Combining the tsetse fly genome with disease control Lessons from triatomine bugs: Chagas disease control SNP diversity Cool phylogenomics Tsetse fly 1](https://reader030.vdocuments.net/reader030/viewer/2022032804/56649e575503460f94b4f872/html5/thumbnails/20.jpg)
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