A sampling algorithm for segregation analysis

Methods for detecting Quantitative Trait Loci (QTL) without markers have generally used iterative peeling algorithms for determining genotype probabilities. These algorithms have considerable shortcomings in complex pedigrees. A Monte Carlo Markov chain (MCMC) method which samples the pedigree of the whole population jointly is described. Simultaneous sampling of the pedigree was achieved by sampling descent graphs using the Metropolis-Hastings algorithm. A descent graph describes the inheritance state of each allele and provides pedigrees guaranteed to be consistent with Mendelian sampling. Sampling descent graphs overcomes most, if not all, of the limitations incurred by iterative peeling algorithms. The algorithm was able to find the QTL in most of the simulated populations. However, when the QTL was not modeled or found then its effect was ascribed to the polygenic component. No QTL were detected when they were not simulated

Parallel computations on pedigree data through mapping to configurable computing devices

Pedigree data structures have a number of applications in genetics, including the estimation of allelic or haplotype probabilities in humans and agricultural species, and the estimation of breeding values in agricultural species. Sequential algorithms for general purpose CPU-based computers are commonly used, but are inadequate for some tasks on large data sets. We show that pedigree data can be directly represented on Field Programmable Gate Arrays (FPGA), allowing highly efficient massively parallel simulation of the flow of genes. Operating on the whole pedigree in parallel, the transmission of genes can occur for all individuals in a single clock cycle. By using FPGA, the algorithms to estimate inbreeding coefficients and allelic probabilities are shown to operate hundreds to thousands of times faster than the corresponding sequentially based algorithms. Where problems can be largely represented in an integer form, FPGA provide an efficient platform for computations on pedigree data

Kinetics of intramolecular catalysis.

The ‘mixed’ acid dissociation constant values for a series of substituted aromatic ortho-acetyl carboxylic acids and one alicyclic ortho-acetylcarboxylic acid have been measured in water at 25°C. The ’true’ acid dissociation constant values have been found by first determining the catalytic constant for the decomposition of nitramide by the keto-acid anion in water at 25°C and then comparing these results with those already obtained for some simple carboxylic acids whose acid dissociation constants are known. The values obtained were checked in a few cases by determining the catalytic constants for the mutarotation of glucose in water at 18°C and comparing these with values already obtained for some simple carboxylic acids. Comparison of the ’mixed’ and ’true’ acid dissociation constants have been made and the percentage of ring-chain tautomerism for each keto-acid determined. Infra red data for each keto-acid are also provided. Rate constants for the intramolecular base catalysed enolization have been determined in water at 25°C and rate constants have also been obtained for intermolecular catalysis by acetate ions and pyridine. The reactions have been followed by recording spectrophotometrically the disappearance of tri-iodide at 353 nm. Some attempt has been made to relate the structure of the keto-acid to the rate of enolization. The rate for the bimolecular reaction involving two keto-acid anions has been estimated for each keto-acid and this value compared with that observed for the intramolecular base catalysed reaction. From these data the effectiveness of the intramolecular process compared to that of the intermolecular process has been estimated and is discussed in terms of effective molarity, c. The intermolecular processes involving pyridine and acetate ions have been compared in an attempt to estimate qualitatively steric effects associated with the acetyl group. Possible alternative mechanisms to explain apparent intramolecular catalysis are also suggested

Factors influencing the efficiency of a marker-assisted introgression programme in Merino sheep

This study investigated a marker-assisted introgression programme in Australian Merino sheep. The goal was to introgress an allele with a large negative effect on fibre diameter into a Merino flock possessing medium average fibre diameter. The influence of two factors was explored: the strategy used to select animals from the purebred and backcross line for backcrossing purposes and the use of selection on background markers to accelerate the return to the purebred line's genome. The results were compared to introgression based on EBVs only. Introgression using EBVs only produced almost the same response in the dollar index as marker-based introgression methods. However, this study did not account for some of the costs associated with implementing the programmes, including the costs of phenotyping and genotyping. Given that the cost of measuring fibre diameter is low, it was concluded that introgression on EBVs only would be the preferred method since the marginal profit of marker-assisted introgression would not be large enough to cover the additional cost of genotyping. In marker-assisted introgression, reciprocal crossing of male and female selection candidates from the backcross and the purebred line was the most advantageous strategy from a practical and profit point of view. Selection for background markers was less profitable in this study than recovering the donor genome by selection on phenotype

An Algorithm for Sampling Descent Graphs in Large Complex Pedigrees Efficiently

No exact method for determining genotypic and identity-by-descent probabilities is available for large, complex pedigrees. Approximate methods for such pedigrees cannot be guaranteed to be unbiased. Anew method is proposed that uses the Metropolis-Hastings algorithm to sample a Markov Chain of descent graphs which fit the pedigree and known genotypes. Unknown genotypes are determined from each descent graph. Genotypic probabilities are estimated as their means. The algorithm is shown to be unbiased for small, complex pedigrees and feasible and consistent for large complex pedigrees

Use of genomic information to exploit genotype-by-environment interactions for body weight of broiler chicken in bio-secure and production environments

International audienceAbstractBackgroundThe increase in accuracy of prediction by using genomic information has been well-documented. However, benefits of the use of genomic information and methodology for genetic evaluations are missing when genotype-by-environment interactions (G × E) exist between bio-secure breeding (B) environments and commercial production (C) environments. In this study, we explored (1) G × E interactions for broiler body weight (BW) at weeks 5 and 6, and (2) the benefits of using genomic information for prediction of BW traits when selection candidates were raised and tested in a B environment and close relatives were tested in a C environment.MethodsA pedigree-based best linear unbiased prediction (BLUP) multivariate model was used to estimate variance components and predict breeding values (EBV) of BW traits at weeks 5 and 6 measured in B and C environments. A single-step genomic BLUP (ssGBLUP) model that combined pedigree and genomic information was used to predict EBV. Cross-validations were based on correlation, mean difference and regression slope statistics for EBV that were estimated from full and reduced datasets. These statistics are indicators of population accuracy, bias and dispersion of prediction for EBV of traits measured in B and C environments. Validation animals were genotyped and non-genotyped birds in the B environment only.ResultsSeveral indications of G × E interactions due to environmental differences were found for BW traits including significant re-ranking, heterogeneous variances and different heritabilities for BW measured in environments B and C. The genetic correlations between BW traits measured in environments B and C ranged from 0.48 to 0.54. The use of combined pedigree and genomic information increased population accuracy of EBV, and reduced bias of EBV prediction for genotyped birds compared to the use of pedigree information only. A slight increase in accuracy of EBV was also observed for non-genotyped birds, but the bias of EBV prediction increased for non-genotyped birds.ConclusionsThe G × E interaction was strong for BW traits of broilers measured in environments B and C. The use of combined pedigree and genomic information increased population accuracy of EBV substantially for genotyped birds in the B environment compared to the use of pedigree information only

Recommendations for improving follow-up care for mesothelioma patients: A qualitative study comprising documentary analysis, interviews and consultation meetings

Objectives. The study aim was to explore experiences of patients with pleural mesothelioma of follow-up care in three National Health Service (NHS) Trusts to develop recommendations for practice. Design. The study design was qualitative and comprised three interlinked phases: a documentary analysis, interviews and consultation meetings. Altheide and Johnson’s Analytic Realism theoretical framework guided the thematic data analysis process. Setting. The study was conducted in three NHS Trusts in South England. Two were secondary care settings and the third was a tertiary centre. Participants. The secondary care trusts saw 15–20 patients with new mesothelioma per year and the tertiary centre 30–40. The tertiary centre had a designated mesothelioma team. Twenty-one patients met the inclusion criteria: >18 years, mesothelioma diagnosis and in follow-up care. Non-English speaking participants, those unable to provide written informed consent or those whom the clinical team felt would find participation too distressing were excluded. All participants were white, 71% were 70–79 years old and 71% were men. Three consultation meetings were conducted with key stakeholders including mesothelioma nurse specialists, patients with mesothelioma, carers and local clinical commissioning group members. Main outcome measures. Specific outcomes were to gain a detailed understanding of mesothelioma follow-up care pathways and processes and to develop coproduced recommendations for practice. Results. Mesothelioma pathways were not always distinct from lung cancer care pathways. All trusts provided follow-up information and resources but there was varied information on how to access local support groups, research or clinical trial participation. Five themes were developed relating to people; processes; places; purpose and perception of care. Coproduced recommendations for improving mesothelioma follow-up pathways were developed following the consultation meetings. Conclusions. This study has developed recommendations which identify the need for patients with pleural mesothelioma to access consistent, specialist, streamlined mesothelioma care, centred around specialist mesothelioma nurses and respiratory consultants, with input from the wider multidisciplinary team

Genetic parameters for body weight and different definitions of residual feed intake in broiler chickens

International audienceBackground :The objectives of this study were to (1) simultaneously estimate genetic parameters for BW, feed intake (FI), and body weight gain (Gain) during a FI test in broiler chickens using multi-trait Bayesian analysis; (2) derive phe-notypic and genetic residual feed intake (RFI) and estimate genetic parameters of the resulting traits; and (3) compute a Bayesian measure of direct and correlated superiority of a group selected on phenotypic or genetic residual feed intake. A total of 56,649 male and female broiler chickens were measured at one of two ages ( t or t−6 days). BW, FI, and Gain of males and females at the two ages were considered as separate traits, resulting in a 12-trait model. Phenotypic RFI ( RFIP ) and genetic RFI ( RFIG ) were estimated from a conditional distribution of FI given BW and Gain using partial phenotypic and partial genetic regression coefficients, respectively.Results : Posterior means of heritability for BW, FI and Gain were moderately high and estimates were significantly different between males and females at the same age for all traits. In addition, the genetic correlations between male and female traits at the same age were significantly different from 1, which suggests a sex-by-genotype interaction. Genetic correlations between RFIP and RFIG were significantly different from 1 at an older age but not at a younger age.Conclusions :The results of the multivariate Bayesian analyses in this study showed that genetic evaluation for pro-duction and feed efficiency traits should take sex and age differences into account to increase accuracy of selection and genetic gain. Moreover, for communicating with stakeholders, it is easier to explain results from selection on RFIGthan selection on RFIP , since RFIG is genetically independent of production traits and it explains the efficiency of birds in nutrient utilization independently of energy requirements for production and maintenanc