PubMed Health⌕ Search

Biomedical subjects

A W George

Publications and source records attributed to A W George.

6 recordsLinked to original sources

Mapping quantitative trait loci in complex pedigrees: a two-step variance component approach.

There is a growing need for the development of statistical techniques capable of mapping quantitative trait loci (QTL) in general outbred animal populations. Presently used variance component methods, which correctly account for the complex relationships that may exist between individuals, are challenged by the difficulties incurred through unknown marker genotypes, inbred individuals, partially or unknown marker phases, and multigenerational data. In this article, a two-step variance component approach that enables practitioners to routinely map QTL in populations with the aforementioned difficulties is explored. The performance of the QTL mapping methodology is assessed via its application to simulated data. The capacity of the technique to accurately estimate parameters is examined for a range of scenarios.

Animals↗

Localization of a quantitative trait locus via a Bayesian approach.

A Bayesian approach to the direct mapping of a quantitative trait locus (QTL), fully utilizing information from multiple linked gene markers, is presented in this paper. The joint posterior distribution (a mixture distribution modeling the linkage between a biallelic QTL and N gene markers) is computationally challenging and invites exploration via Markov chain Monte Carlo methods. The parameter's complete marginal posterior densities are obtained, allowing a diverse range of inferences. Parameters estimated include the QTL genotype probabilities for the sires and the offspring, the allele frequencies for the QTL, and the position and additive and dominance effects of the QTL. The methodology is applied through simulation to a half-sib design to form an outbred pedigree structure where there is an entire class of missing information. The capacity of the technique to accurately estimate parameters is examined for a range of scenarios.

Algorithms↗

A Bayesian approach to ordering gene markers.

A technique is presented whereby a marker map can be constructed using resource family data with an entire class of missing data. The focus is on a half-sib design where there is only information on a single parent and its progeny. A Bayesian approach is utilised with solutions obtained via a Markov chain Monte Carlo algorithm. Features of the approach include the capacity to determine parameters for the ungenotyped dam population, the ability to incorporate published information and its reliability, and the production of posterior densities and the consequent deduction of a wide range of inferences. These features are demonstrated through the analysis of simulated and experimental data.

Algorithms↗

Sexual practices among patients with borderline personality disorder.

The authors found that 12 (57%) of 21 consecutive male patients with borderline personality disorder who presented for psychiatric treatment at two distant geographic sites were homosexual. They then obtained the sexual histories of 80 patients who met standardized criteria for borderline disorder and found that 17 (21%) of these patients were homosexual, four (5%) were bisexual, and nine (11%) had diagnoses of paraphilias. Ten (53%) of the 19 men with borderline disorder were homosexual, compared with seven (11%) of the 61 women. Homosexuality was 10 times more common among the men and six times more common among the women with borderline personality disorder than in the general population or in a depressed control group.

Adult↗

A simple and rapid method for calculating identity-by-descent matrices using multiple markers.

A fast, partly recursive deterministic method for calculating Identity-by-Descent (IBD) probabilities was developed with the objective of using IBD in Quantitative Trait Locus (QTL) mapping. The method combined a recursive method for a single marker locus with a method to estimate IBD between sibs using multiple markers. Simulated data was used to compare the deterministic method developed in the present paper with a stochastic method (LOKI) for precision in estimating IBD probabilities and performance in the task of QTL detection with the variance component approach. This comparison was made in a variety of situations by varying family size and degree of polymorphism among marker loci. The following were observed for the deterministic method relative to MCMC: (i) it was an order of magnitude faster; (ii) its estimates of IBD probabilities were found to agree closely, even though it does not extract information when haplotypes are not known with certainty; (iii) the shape of the profile for the QTL test statistic as a function of location was similar, although the magnitude of the test statistic was slightly smaller; and (iv) the estimates of QTL variance was similar. It was concluded that the method proposed provided a rapid means of calculating the IBD matrix with only a small loss in precision, making it an attractive alternative to the use of stochastic MCMC methods. Furthermore, developments in marker technology providing denser maps would enhance the relative advantage of this method.

Animals↗