103 research outputs found

    Effect of manipulating recombination rates on response to selection in livestock breeding programs

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    International audienceBackgroundIn this work, we performed simulations to explore the potential of manipulating recombination rates to increase response to selection in livestock breeding programs.MethodsWe carried out ten replicates of several scenarios that followed a common overall structure but differed in the average rate of recombination along the genome (expressed as the length of a chromosome in Morgan), the genetic architecture of the trait under selection, and the selection intensity under truncation selection (expressed as the proportion of males selected). Recombination rates were defined by simulating nine different chromosome lengths: 0.10, 0.25, 0.50, 1, 2, 5, 10, 15 and 20 Morgan, respectively. One Morgan was considered to be the typical chromosome length for current livestock species. The genetic architecture was defined by the number of quantitative trait variants (QTV) that affected the trait under selection. Either a large (10,000) or a small (1000 or 500) number of QTV was simulated. Finally, the proportions of males selected under truncation selection as sires for the next generation were equal to 1.2, 2.4, 5, or 10 %.ResultsIncreasing recombination rate increased the overall response to selection and decreased the loss of genetic variance. The difference in cumulative response between low and high recombination rates increased over generations. At low recombination rates, cumulative response to selection tended to asymptote sooner and the genetic variance was completely eroded. If the trait under selection was affected by few QTV, differences between low and high recombination rates still existed, but the selection limit was reached at all rates of recombination.ConclusionsHigher recombination rates can enhance the efficiency of breeding programs to turn genetic variation into response to selection. However, to increase response to selection significantly, the recombination rate would need to be increased 10- or 20-fold. The biological feasibility and consequences of such large increases in recombination rates are unknown

    Setting the stage: Upgrade of existing SSBN submarine staging to conform to the new SSGN platform

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    With the end of the Cold War, The United States Navy is seeking to convert its fleet of Nuclear Warhead equipped, Ballistic Submarines to a more useful, more versatile platform. This transformation requires significant changes to the submarine’s sail, the topmost structure of a submarine. The sail houses the submarine’s compliment of missiles as well as the communication equipment and the periscope. In order to accommodate the new platform, additional access ports are being cut into the sail. The addition of these ports is the impudence to our project. When a submarine is in port for repairs, a structure call the “staging” is lowered over the sail. This staging acts as a scaffold from which the maintenance crews can easily utilize the access ports and perform their tasks. Once the changes are made to the submarine, the existing staging will need to be modified. Fifteen new access ports are being added to the sail. Of these ports, ten are not accessible from the current staging, and five are actually obstructed by it. Our team’s task will be to design the necessary modification to the staging allowing it to adapt it to the new platform, while ensuring that it is still backward compatible with as of yet un-renovated submarines. Our design will strive to meet the objectives the Navy has set for success. This project is to be a cost effective as possible in order to minimize costs. Any changes we make must be simple enough as to be quickly effective on each of the Navy's current ports. Above all, our design must ensure for the safety of the workers who will be the end users of the stagin

    AlphaSim: Software for Breeding Program Simulation

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    This paper describes AlphaSim, a software package for simulating plant and animal breeding programs. AlphaSim enables the simulation of multiple aspects of breeding programs with a high degree of flexibility. AlphaSim simulates breeding programs in a series of steps: (i) simulate haplotype sequences and pedigree; (ii) drop haplotypes into the base generation of the pedigree and select single-nucleotide polymorphism (SNP) and quantitative trait nucleotide (QTN); (iii) assign QTN effects, calculate genetic values, and simulate phenotypes; (iv) drop haplotypes into the burn-in generations; and (v) perform selection and simulate new generations. The program is flexible in terms of historical population structure and diversity, recent pedigree structure, trait architecture, and selection strategy. It integrates biotechnologies such as doubled-haploids (DHs) and gene editing and allows the user to simulate multiple traits and multiple environments, specify recombination hot spots and cold spots, specify gene jungles and deserts, perform genomic predictions, and apply optimal contribution selection. AlphaSim also includes restart functionalities, which increase its flexibility by allowing the simulation process to be paused so that the parameters can be changed or to import an externally created pedigree, trial design, or results of an analysis of previously simulated data. By combining the options, a user can simulate simple or complex breeding programs with several generations, variable population structures and variable breeding decisions over time. In conclusion, AlphaSim is a flexible and computationally efficient software package to simulate biotechnology enhanced breeding programs with the aim of performing rapid, low-cost, and objective in silico comparison of breeding technologies

    A method for the allocation of sequencing resources in genotyped livestock populations

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    International audienceAbstractBackgroundThis paper describes a method, called AlphaSeqOpt, for the allocation of sequencing resources in livestock populations with existing phased genomic data to maximise the ability to phase and impute sequenced haplotypes into the whole population.MethodsWe present two algorithms. The first selects focal individuals that collectively represent the maximum possible portion of the haplotype diversity in the population. The second allocates a fixed sequencing budget among the families of focal individuals to enable phasing of their haplotypes at the sequence level. We tested the performance of the two algorithms in simulated pedigrees. For each pedigree, we evaluated the proportion of population haplotypes that are carried by the focal individuals and compared our results to a variant of the widely-used key ancestors approach and to two haplotype-based approaches. We calculated the expected phasing accuracy of the haplotypes of a focal individual at the sequence level given the proportion of the fixed sequencing budget allocated to its family.ResultsAlphaSeqOpt maximises the ability to capture and phase the most frequent haplotypes in a population in three ways. First, it selects focal individuals that collectively represent a larger portion of the population haplotype diversity than existing methods. Second, it selects focal individuals from across the pedigree whose haplotypes can be easily phased using family-based phasing and imputation algorithms, thus maximises the ability to impute sequence into the rest of the population. Third, it allocates more of the fixed sequencing budget to focal individuals whose haplotypes are more frequent in the population than to focal individuals whose haplotypes are less frequent. Unlike existing methods, we additionally present an algorithm to allocate part of the sequencing budget to the families (i.e. immediate ancestors) of focal individuals to ensure that their haplotypes can be phased at the sequence level, which is essential for enabling and maximising subsequent sequence imputation.ConclusionsWe present a new method for the allocation of a fixed sequencing budget to focal individuals and their families such that the final sequenced haplotypes, when phased at the sequence level, represent the maximum possible portion of the haplotype diversity in the population that can be sequenced and phased at that budget

    Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs

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    Abstract Background This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. Methods We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance ( \u3c3 A 2 ) , rate of change in inbreeding ( \u394 F ), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Results Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Conclusions Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding

    Assessment of an in vitro whole cigarette smoke exposure system: The Borgwaldt RM20S 8-syringe smoking machine

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    <p>Abstract</p> <p>Background</p> <p>There have been many recent developments of <it>in vitro </it>cigarette smoke systems closely replicating <it>in vivo </it>exposures. The Borgwaldt RM20S smoking machine (RM20S) enables the serial dilution and delivery of cigarette smoke to exposure chambers for <it>in vitro </it>analyses. In this study we have demonstrated reliability and robustness testing of the RM20S in delivering smoke to <it>in vitro </it>cultures using an in-house designed whole smoke exposure chamber.</p> <p>Results</p> <p>The syringe precision and accuracy of smoke dose generated by the RM20S was assessed using a methane gas standard and resulted in a repeatability error of ≀9%. Differential electrical mobility particle spectrometry (DMS) measured smoke particles generated from reference 3R4F cigarettes at points along the RM20S. 53% ± 5.9% of particles by mass reached the chamber, the remainder deposited in the syringe or connecting tubing and ~16% deposited in the chamber. Spectrofluorometric quantification of particle deposition within chambers indicated a positive correlation between smoke concentration and particle deposition. <it>In vitro </it>air-liquid interface (ALI) cultures (H292 lung epithelial cells), exposed to whole smoke (1:60 dilution (smoke:air, equivalent to ~5 ÎŒg/cm<sup>2</sup>)) demonstrated uniform smoke delivery within the chamber.</p> <p>Conclusions</p> <p>These results suggest this smoke exposure system is a reliable and repeatable method of generating and exposing ALI <it>in vitro </it>cultures to cigarette smoke. This system will enable the evaluation of future tobacco products and individual components of cigarette smoke and may be used as an alternative <it>in vitro </it>tool for evaluating other aerosols and gaseous mixtures such as air pollutants, inhaled pharmaceuticals and cosmetics.</p
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