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      Estimating helminth burdens using sibship reconstruction

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          Abstract

          Background

          Sibship reconstruction is a form of parentage analysis that can be used to identify the number of helminth parental genotypes infecting individual hosts using genetic data on only their offspring. This has the potential to be used for estimating individual worm burdens when adult parasites are otherwise inaccessible, the case for many of the most globally important human helminthiases and neglected tropical diseases. Yet methods of inferring worm burdens from sibship reconstruction data on numbers of unique parental genotypes are lacking, limiting the method’s scope of application.

          Results

          We developed a novel statistical method for estimating female worm burdens from data on the number of unique female parental genotypes derived from sibship reconstruction. We illustrate the approach using genotypic data on Schistosoma mansoni (miracidial) offspring collected from schoolchildren in Tanzania. We show how the bias and precision of worm burden estimates critically depends on the number of sampled offspring and we discuss strategies for obtaining sufficient sample sizes and for incorporating judiciously formulated prior information to improve the accuracy of estimates.

          Conclusions

          This work provides a novel approach for estimating individual-level worm burdens using genetic data on helminth offspring. This represents a step towards a wider scope of application of parentage analysis techniques. We discuss how the method could be used to assist in the interpretation of monitoring and evaluation data collected during mass drug administration programmes targeting human helminthiases and to help resolve outstanding questions on key population biological processes that govern the transmission dynamics of these neglected tropical diseases.

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          Most cited references62

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          COLONY: a program for parentage and sibship inference from multilocus genotype data.

          Pedigrees, depicting genealogical relationships between individuals, are important in several research areas. Molecular markers allow inference of pedigrees in wild species where relationship information is impossible to collect by observation. Marker data are analysed statistically using methods based on Mendelian inheritance rules. There are numerous computer programs available to conduct pedigree analysis, but most software is inflexible, both in terms of assumptions and data requirements. Most methods only accommodate monogamous diploid species using codominant markers without genotyping error. In addition, most commonly used methods use pairwise comparisons rather than a full-pedigree likelihood approach, which considers the likelihood of the entire pedigree structure and allows the simultaneous inference of parentage and sibship. Here, we describe colony, a computer program implementing full-pedigree likelihood methods to simultaneously infer sibship and parentage among individuals using multilocus genotype data. colony can be used for both diploid and haplodiploid species; it can use dominant and codominant markers, and can accommodate, and estimate, genotyping error at each locus. In addition, colony can carry out these inferences for both monoecious and dioecious species. The program is available as a Microsoft Windows version, which includes a graphical user interface, and a Macintosh version, which uses an R-based interface. © 2009 Blackwell Publishing Ltd.
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            Control of neglected tropical diseases.

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              Parentage and sibship inference from multilocus genotype data under polygamy.

              Likelihood methods have been developed to partition individuals in a sample into sibling clusters using genetic marker data without parental information. Most of these methods assume either both sexes are monogamous to infer full sibships only or only one sex is polygamous to infer full sibships and paternal or maternal (but not both) half sibships. We extend our previous method to the more general case of both sexes being polygamous to infer full sibships, paternal half sibships, and maternal half sibships and to the case of a two-generation sample of individuals to infer parentage jointly with sibships. The extension not only expands enormously the scope of application of the method, but also increases its statistical power. The method is implemented for both diploid and haplodiploid species and for codominant and dominant markers, with mutations and genotyping errors accommodated. The performance and robustness of the method are evaluated by analyzing both simulated and empirical data sets. Our method is shown to be much more powerful than pairwise methods in both parentage and sibship assignments because of the more efficient use of marker information. It is little affected by inbreeding in parents and is moderately robust to nonrandom mating and linkage of markers. We also show that individually much less informative markers, such as SNPs or AFLPs, can reach the same power for parentage and sibship inferences as the highly informative marker simple sequence repeats (SSRs), as long as a sufficient number of loci are employed in the analysis.
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                Author and article information

                Contributors
                mneves@rvc.ac.uk
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                16 September 2019
                16 September 2019
                2019
                : 12
                : 441
                Affiliations
                [1 ]ISNI 0000 0001 2161 2573, GRID grid.4464.2, Department of Pathobiology and Population Sciences, Royal Veterinary College, , University of London, ; Hawkshead Lane, Hatfield, UK
                [2 ]London Centre for Neglected Tropical Disease Research, London, UK
                Author information
                http://orcid.org/0000-0002-9887-6339
                Article
                3687
                10.1186/s13071-019-3687-1
                6745796
                31522688
                6ec4f14f-c874-4360-859e-5eb07b32a573
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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
                : 3 May 2019
                : 28 August 2019
                Funding
                Funded by: Royal Veterinary College, University of London
                Award ID: PhD Scholarship
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Parasitology
                parentage analysis,sibship reconstruction,worm burden,schistosomiasis,neglected tropical diseases

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