Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites

Frédéric D. Chevalier, Claudia L.L. Valentim, Philip T. LoVerde, Timothy J.C. Anderson

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: Identification of parasite genes that underlie traits such as drug resistance and host specificity is challenging using classical linkage mapping approaches. Extreme QTL (X-QTL) methods, originally developed by rodent malaria and yeast researchers, promise to increase the power and simplify logistics of linkage mapping in experimental crosses of schistosomes (or other helminth parasites), because many 1000s of progeny can be analysed, phenotyping is not required, and progeny pools rather than individuals are genotyped. We explored the utility of this method for mapping a drug resistance gene in the human parasitic fluke Schistosoma mansoni.Results: We staged a genetic cross between oxamniquine sensitive and resistant parasites, then between two F1 progeny, to generate multiple F2 progeny. One group of F2s infecting hamsters was treated with oxamniquine, while a second group was left untreated. We used exome capture to reduce the size of the genome (from 363 Mb to 15 Mb) and exomes from pooled F2 progeny (treated males, untreated males, treated females, untreated females) and the two parent parasites were sequenced to high read depth (mean = 95-366×) and allele frequencies at 14,489 variants compared. We observed dramatic enrichment of alleles from the resistant parent in a small region of chromosome 6 in drug-treated male and female pools (combined analysis: Z = 11.07, p = 8.74 × 10-29). This region contains Smp_089320 a gene encoding a sulfotransferase recently implicated in oxamniquine resistance using classical linkage mapping methods.Conclusions: These results (a) demonstrate the utility of exome capture for generating reduced representation libraries in Schistosoma mansoni, and (b) provide proof-of-principle that X-QTL methods can be successfully applied to an important human helminth. The combination of these methods will simplify linkage analysis of biomedically or biologically important traits in this parasite.

Original languageEnglish (US)
Article number617
JournalBMC genomics
Volume15
Issue number1
DOIs
StatePublished - Jul 21 2014

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Keywords

  • Exome capture
  • NGS
  • Oxamniquine resistance
  • Schistosoma mansoni
  • X-QTL

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Chevalier, F. D., Valentim, C. L. L., LoVerde, P. T., & Anderson, T. J. C. (2014). Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites. BMC genomics, 15(1), [617]. https://doi.org/10.1186/1471-2164-15-617