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Biomedical subjects

M S Ridout

Publications and source records attributed to M S Ridout.

12 recordsLinked to original sources

Analysis of segregation data from selfed progeny of allopolyploids.

This paper discusses the inference of parental genotype based on segregation data from selfed progeny of allopolyploids when there is incomplete information about genotypes and when alleles are codominant or null. The distinct alleles that are present in a genotype are assumed to be known, but not the frequency with which they occur. These assumptions may be appropriate when genotypes are deduced from DNA or protein banding patterns on electrophoretic gels. A computer program, SELF, is described that can generate all possible parental genotypes and rank them on the basis of their agreement with the progeny data. The program caters for tetraploids, hexaploids and octoploids. The methods are illustrated using data from a study of the inheritance of isoenzymes in selfed progeny of octoploid strawberry cultivars.

Alleles↗

Polylink: to support two-point linkage analysis in autotetraploids.

SUMMARY: Polylink runs under Microsoft Windows (95 or later). It performs various calculations that are useful for investigating two-point linkage analysis for autopolyploids, based on the random chromosome pairing model. These include calculation of offspring phenotypic probabilities as functions of the recombination fraction, calculation of theoretical standard errors for the maximum likelihood estimator of and numerical computation of maximum likelihood estimates. It also includes simulation facilities. AVAILABILITY: Polylink is free and available from Xiangming Xu via email

Computational Biology↗

Cation permeability and selectivity of a root plasma membrane calcium channel.

Calcium channels in the plasma membrane of root cells fulfill both nutritional and signaling roles. The permeability of these channels to different cations determines the magnitude of their cation conductances, their effects on cell membrane potential and their contribution to cation toxicities. The selectivity of the rca channel, a Ca2+-permeable channel from the plasma membrane of wheat (Triticum aestivum L.) roots, was studied following its incorporation into planar lipid bilayers. The permeation of K+, Na+, Ca2+ and Mg2+ through the pore of the rca channel was modeled. It was assumed that cations permeated in single file through a pore with three energy barriers and two ion-binding sites. Differences in permeation between divalent and monovalent cations were attributed largely to the affinity of the ion binding sites. The model suggested that significant negative surface charge was present in the vestibules to the pore and that the pore could accommodate two cations simultaneously, which repelled each other strongly. The pore structure of the rca channel appeared to differ from that of L-type calcium channels from animal cell membranes since its ion binding sites had a lower affinity for divalent cations. The model adequately accounted for the diverse permeation phenomena observed for the rca channel. It described the apparent submillimolar Km for the relationship between unitary conductance and Ca2+ activity, the differences in selectivity sequences obtained from measurements of conductance and permeability ratios, the changes in relative cation permeabilities with solution ionic composition, and the complex effects of Ca2+ on K+ and Na+ currents through the channel. Having established the adequacy of the model, it was used to predict the unitary currents that would be observed under the ionic conditions employed in patch-clamp experiments and to demonstrate the high selectivity of the rca channel for Ca2+ influx under physiological conditions.

Calcium↗

An energy-barrier model for the permeation of monovalent and divalent cations through the maxi cation channel in the plasma membrane of rye roots.

The depolarization-activated, high-conductance "maxi" cation channel in the plasma membrane of rye (Secale cereale L.) roots is permeable to a wide variety of monovalent and divalent cations. The permeation of K+, Na+, Ca2+ and Ba2+ through the pore could be simulated using a model composed of three energy barriers and two ion binding sites (a 3B2S model), which assumed single-file permeation and the possibility of double cation occupancy. The model had an asymmetrical free energy profile. Differences in permeation between cations were attributed primarily to differences in their free energy profiles in the regions of the pore adjacent to the extracellular solution. In particular, the height of the central free energy peak differed between cations, and cations differed in their affinities for ion binding sites. Significant ion repulsion occurred within the pore, and the mouths of the pore had considerable surface charge. The model adequately described the diverse current vs. voltage (I/V) relationships obtained over a wide variety of experimental conditions. It described the phenomena of non-Michaelian unitary conductance vs. activity relationships for K+, Na+ and Ca2+, differences in selectivity sequences obtained from measurements of conductance and permeability ratios, changes in relative cation permeabilities with solution composition, and the complex effects of Ba2+ and Ca2+ on K+ currents through the channel. The model enabled the prediction of unitary currents and ion fluxes through the maxi cation channel under physiological conditions. It could be used, in combination with data on the kinetics of the channel, as input to electrocoupling models allowing the relationships between membrane voltage, Ca2+ influx and Ca2+ signaling to be studied theoretically.

Barium↗

Estimating intraclass correlation for binary data.

This paper reviews many different estimators of intraclass correlation that have been proposed for binary data and compares them in an extensive simulation study. Some of the estimators are very specific, while others result from general methods such as pseudo-likelihood and extended quasi-likelihood estimation. The simulation study identifies several useful estimators, one of which does not seem to have been considered previously for binary data. Estimators based on extended quasi-likelihood are found to have a substantial bias in some circumstances.

Biometry↗

Memory in coal tits: an alternative model.

Jolliffe and Jolliffe (1997, Biometrics 53, 1136-1142) proposed various models for data from an experiment on memory in coal tits. This article describes an alternative model, which fits equally well and which may be simpler to interpret.

Algorithms↗

The estimation of rapid rate constants from current-amplitude frequency distributions of single-channel recordings.

A method is described for estimating rapid rate constants from the distributions of current amplitude observed in single-channel electrical recordings. It has the advantages over previous, similar approaches that it can accommodate both multistate kinetic models and adjustable filtering of the data using an 8-pole Bessel filter. The method is conceptually straightforward: the observed distributions of current amplitude are compared with theoretical distributions derived by combining several simplifying assumptions about the underlying stochastic process with a model of the filter and electrical noise. Parameters are estimated by approximate maximum likelihood. The method was used successfully to estimate rate constants for both a simple two-state kinetic model (the transitions between open and closed states during the rapid gating of an outward-rectifying K(+)-selective channel in the plasma membrane of Acetabularia) and a complex multistate kinetic model (the blockade of the maxi cation channel in the plasma membrane of rye roots by verapamil). For the two-state model, parameters were estimated well, provided that they were not too fast or too slow in relation to the sampling rate. In the three-state model the precision of estimates depended in a complex way on the values of all rate parameters in the model.

Acetabularia↗

Finite mixture models for proportions.

Six data sets recording fetal control mortality in mouse litters are presented. The data are clearly overdispersed, and a standard approach would be to describe the data by means of a beta-binomial model or to use quasi-likelihood methods. For five of the examples, we show that beta-binomial model provides a reasonable description but that the fit can be significantly improved by using a mixture of a beta-binomial model with a binomial distribution. This mixture provides two alternative solutions, in one of which the binomial component indicates a high probability of death but is selected infrequently; this accounts for outlying litters with high mortality. The influence of the outliers on the beta-binomial fits is also demonstrated. The location and nature of the two main maxima to the likelihood are investigated through profile log-likelihoods. Comparisons are made with the performance of finite mixtures of binomial distributions.

Animals↗

Modelling digit preference in fecundability studies.

Retrospective studies of fecundability, in which women are asked how many cycles they required to become pregnant, are often affected by problems of digit preference. A probability model for such digit preference is proposed in which misreporting favours 6 or 12 (and possibly also 3) cycles. It is assumed that in the absence of misreporting the number of cycles follows a beta-geometric distribution. The model is applied to two data sets, with clear-cut results: The inclusion of additional parameters to model the misreporting can lead to substantial improvements in fit, but causes little change to the estimated parameters of the underlying beta-geometric distribution. In some cases misreporting parameters may be regarded as nuisance parameters, while in others they may be of interest. We have found estimates of these parameters to vary between different categories of women in an interpretable manner. The models may also be used to estimate the percentage of couples in any study that misreport their conception waiting time.

Biometry↗

Testing for random dropouts in repeated measurement data.

Diggle (1989, Biometrics 45, 1255-1258) proposes a test for random dropouts in repeated measurement data when the experiment has a completely randomized design. It is argued here that logistic regression is a comparable but more flexible technique for studying the occurrence of dropouts.

Animals↗

Improved estimation of the proportion of triploids in populations with diploid and triploid individuals.

We consider the estimation of the proportion of triploids in populations of plants or animals in which diploid and triploid individuals coexist, using data from electrophoretic analysis of isozyme or microsatellite markers. Individuals that have three distinct alleles at a locus are unambiguously triploid. However, other individuals cannot be classified with certainty as diploid or triploid, unless allelic dosage can be determined reliably. This is impossible for microsatellite markers, and for many isozyme markers. We therefore present a maximum likelihood method of estimating the proportion of triploids based only on the presence or absence of different alleles.

Alleles↗