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

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          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: = 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.

          Electronic supplementary material

          The online version of this article (doi:10.1186/1471-2164-15-617) contains supplementary material, which is available to authorized users.

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          Most cited references38

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          Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

          An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.
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            R: a language and environment for statistical computing

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              The global status of schistosomiasis and its control.

              Schistosomiasis is being successfully controlled in many countries but remains a major public health problem, with an estimated 200 million people infected, mostly in Africa. Few countries in this region have undertaken successful and sustainable control programmes. The construction of water schemes to meet the power and agricultural requirements for development have lead to increasing transmission, especially of Schistosoma mansoni. Increasing population and movement have contributed to increased transmission and introduction of schistosomiasis to new areas. Most endemic countries are among the least developed whose health systems face difficulties to provide basic care at the primary health level. Constraints to control include, the lack of political commitment and infrastructure for public health interventions. Another constraint is that available anti-schistosomal drugs are expensive and the cost of individual treatment is a high proportion of the per capita drug budgets. There is need for increased support for schistosomiasis control in the most severely affected countries.
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                Author and article information

                Contributors
                fcheval@txbiomedgenetics.org
                valentim@livemail.uthscsa.edu
                loverde@uthscsa.edu
                tanderso@txbiomedgenetics.org
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                21 July 2014
                21 July 2014
                2014
                : 15
                : 1
                : 617
                Affiliations
                [ ]Department of Genetics, Texas Biomedical Research Institute, P.O. Box 760549, 78245 San Antonio, Texas USA
                [ ]Departments of Biochemistry and Pathology, University of Texas Health Science Center, 78229-3900 San Antonio, Texas USA
                Article
                6296
                10.1186/1471-2164-15-617
                4117968
                25048426
                c6183ff2-40d7-480c-b86c-8b9d0d34bb3c
                © Chevalier et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 March 2014
                : 14 July 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Genetics
                x-qtl,exome capture,schistosoma mansoni,oxamniquine resistance,ngs
                Genetics
                x-qtl, exome capture, schistosoma mansoni, oxamniquine resistance, ngs

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