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Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing.

ABSTRACT: Small, isolated populations are constantly threatened by loss of genetic diversity due to drift. Such situations are found, for instance, in laboratory culturing. In guarding against diversity loss, monitoring of potential changes in population structure is paramount; this monitoring is most often achieved using microsatellite markers, which can be costly in terms of time and money when many loci are scored in large numbers of individuals. Here, we present a case study reducing the number of microsatellites to the minimum necessary to correctly detect the population structure of two Drosophila nigrosparsa populations. The number of loci was gradually reduced from 11 to 1, using the Allelic Richness (AR) and Private Allelic Richness (PAR) as criteria for locus removal. The effect of each reduction step was evaluated by the number of genetic clusters detectable from the data and by the allocation of individuals to the clusters; in the latter, excluding ambiguous individuals was tested to reduce the rate of incorrect assignments. We demonstrate that more than 95% of the individuals can still be correctly assigned when using eight loci and that the major population structure is still visible when using two highly polymorphic loci. The differences between sorting the loci by AR and PAR were negligible. The method presented here will most efficiently reduce genotyping costs when small sets of loci ("core sets") for long-time use in large-scale population screenings are compiled.

SUBMITTER: Arthofer W

PROVIDER: S-EPMC5927656 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing.

Arthofer Wolfgang W Heussler Carina C Krapf Patrick P Schlick-Steiner Birgit C BC Steiner Florian M FM

Fly 20171201 1

Small, isolated populations are constantly threatened by loss of genetic diversity due to drift. Such situations are found, for instance, in laboratory culturing. In guarding against diversity loss, monitoring of potential changes in population structure is paramount; this monitoring is most often achieved using microsatellite markers, which can be costly in terms of time and money when many loci are scored in large numbers of individuals. Here, we present a case study reducing the number of mic ...[more]

PMID: 29166845

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Project description:Objective:Schizophrenia clinical trials commonly measure observed changes in Positive and Negative Syndrome Scale (PANSS) total score. However, it is more intuitive to think of response vs nonresponse, a binary outcome. Assessing binary outcomes enables calculation of number needed to treat (NNT) for therapeutic outcomes, number needed to harm (NNH) for adverse outcomes, and likelihood to be helped or harmed (LHH) to demonstrate benefit/risk tradeoffs. Here, NNT, NNH, and LHH were used to evaluate the clinical usefulness of aripiprazole lauroxil in patients with an acute schizophrenia exacerbation. Methods:Categorical efficacy and tolerability data were taken from the pivotal Phase 3 trial evaluating aripiprazole lauroxil for treatment of an acute exacerbation of schizophrenia. NNT and NNH values, with 95% CIs, were calculated in this post hoc analysis. Results:Using the intent-to-treat population for the pooled doses of aripiprazole lauroxil (441 mg [n=196] and 882 mg [n=204] q4w), responder rates (?30% improvement from baseline PANSS total score) were 35.3% for aripiprazole lauroxil arms vs 18.4% for placebo (n=196), yielding a NNT of 6 (95% CI: 5-11). Discontinuation rates due to adverse events (AEs) were higher among patients randomized to placebo than to either aripiprazole lauroxil dose. Akathisia was the only AE with an incidence ?5% in each aripiprazole lauroxil group and at least twice that of placebo (11.6%, 11.5%, and 4.3% of the patients receiving aripiprazole lauroxil 441 mg, 882 mg, and placebo, respectively), producing a NNH of 14 (95% CI: 9-33) for pooled aripiprazole lauroxil doses vs placebo. Calculating LHH for therapeutic response vs akathisia, aripiprazole lauroxil was 2.3 times more likely to result in a therapeutic response than an incident of akathisia. Conclusion:Using metrics of NNT, NNH, and LHH, aripiprazole lauroxil was an efficacious and well-tolerated intervention in a pivotal study in patients with an acute schizophrenia exacerbation.

Dataset Information

Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing.

Publications

Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing.

Similar Datasets

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