Cw nelson scarcii

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Cw nelson scarcii

  1. 1. Using GIS to analyze genetic variationin pathogen populations: a case studywith Plasmodium falciparumCHASE W. NELSONUSC, Department of Biological SciencesAdvisor: Dr. Austin L. Hughes11 FEBRUARY 2012
  2. 2. Background Gene: a stretch of DNA that encodes one product (i.e., RNA or protein)
  3. 3. BackgroundDNATranscriptionTranslationProteinmRNARNA
  4. 4. Background Central DogmaGene 2Gene 1 Gene 3Copyright © Roche Genetics Education Program.
  5. 5. Background Gene: a stretch of DNA that encodes one trait Mutation: random changes in DNA sequence Synonymous changes: “silent” neutral changes Nonsynonymous changes: functional divergence
  6. 6. The code is redundant
  7. 7. Background Gene: a stretch of DNA that encodes one product (i.e., a ncRNA or protein) Mutation: random changes in DNA sequence Synonymous changes: “silent” neutral changes Nonsynonymous changes: functional divergenceCTA  LeucineCTC  LeucineCTG  LeucineCTT  LeucineAGA  ArginineAGC  SerineAGG  ArginineAGT  Serine
  8. 8. Natural selectionNATURAL SELECTIONPURIFYINGSELECTIONPOSITIVESELECTIONMUTATION
  9. 9. Background Malaria Major global health issue Kills 1 million per year >216 million cases in 2010 (Howitt et al. 2012) No effective vaccine Sporozoite stage Circumsporozoite protein (CSP) 5’NR – NANP repeat region – 3’NRImage obtained from: Cowman & Crabb (2006).
  10. 10. Background Malaria Major global health issue Kills 1 million per year >216 million cases in 2010 (Howitt et al. 2012) No effective vaccine Sporozoite stage Circumsporozoite protein (CSP) 5’NR – NANP repeat region – 3’NRImage obtained from: http://www.pnas.org/content/109/4/999/F1.large.jpg
  11. 11. Literature Jongwutiwes et al.2010
  12. 12. Methods Obtained P. falciparium circumsporozoite protein (CSP) sequences BLAST Dame et al. (1984) GI:160160 448 / 665 hits had 100% coverage 1 full chromosome 443 could be located by exhaustive literature review Bioinformatics Alignment with ClustalW
  13. 13. Data All 447 sequences were traced to geographic origin by: GenBank annotations Extensive literature review Contact with study authorsCOUNTRY NO. REGION(S) Lat LongBrazil 2 Manaus, Amazonas -3.1292 -60.0214Cameroon 9 Yaounde 3.8667 11.5167China 1 Hainan Province 19.1067 109.5675El Salvador 1 Cangrejera 13.4667 -89.1753Gambia 44 Farafenni 13.5667 -15.6Ghana 1 Accra 5.55 -0.2167Honduras 1 Honduras 14.7806 -87.4384India 11 Assam 26 93Kenya 18 Asembo Bay, Western Kenya -0.1831 34.3839Laos 1 Laos 18.2912 103.6069Nigeria 1 Lagos 6.45 3.3833P.N. Guinea 2 Madang Province -5.2269 145.7939Thailand 335 Kanchanaburi, et al. 14.0225 99.5317Unknown 4 NoData NoData NoDataVanuatu 6 Malakula -16.3 167.5Venezuela 10 Amazonas, etc. 3.5 -66TOTAL 447 27 distinct regions + NoData
  14. 14. Model Two goals DNA sequence interpolation Nearest Neighbor Detect spatial autocorrelation Moran’s IdPij =
  15. 15. Moran’s I Spatial autocorrelation
  16. 16. Model User provides ArcGIS with: Basemap, e.g., World Street Map (WGS 1984) Land map, e.g., World Continents (WGS 1984) Spreadsheet with sequences Latitude and Longitude Proportion difference (e.g., pRefDiff) 443C2 = 97,903 Nucleotides at each site (e.g., Site_i)
  17. 17. Add XY DataDraw ThiessenPolygonsClipGenetic TableWith XYSampleLocationsSequencePolygonsLand LimitedPolygonsLand AreaAdd fieldsConcatenate SitesFull Sequenceand dP FieldsFull SequenceJukes-CantorCorrectedDistance (dP)Moran’s I0147 8 952+/- .36/*-+CE C0147 8 952+/- .36/*-+CE CMoran’s I
  18. 18. Sources: Esri, DeLorme, NAVTEQ, USGS, Intermap, iPC, NRCAN, Esri Japan, METI, Esri China (Hong Kong), Esri(Thailand), TomTom, 2012
  19. 19. Sources: Esri, DeLorme, NAVTEQ, USGS, Intermap, iPC, NRCAN, Esri Japan, METI, Esri China (Hong Kong), Esri(Thailand), TomTom, 2012
  20. 20. ResultsALLNo NW RedundNo Redund
  21. 21. Discussion Model extremely brittle: implement wild cards for sites in Python Incorporate sequences without full coverage Thiessen polygons for each site? Devise strategy to handle thousands of nucleotide sites Define another reference sequence or all pairwise comparisons
  22. 22. Discussion Moran’s I across or within specific regions Moran’s I interpretation Ultimate: use genetic and spatial data to control malaria
  23. 23. Acknowledgments Dr. Austin L. Hughes USC Geography Department Michael E. Hodgson Erica Pfister-Altschul Lynn Shirley
  24. 24. finis

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