Biomedical subjects
M Kirkpatrick
Publications and source records attributed to M Kirkpatrick.
Prevention vs cure in developing countries.
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Direct selection of female mating preferences: comments on Grafen's models.
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Is the prevalence of childhood hearing impairment over-estimated in developing countries?
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Selection response in traits with maternal inheritance.
Maternal inheritance is the non-Mendelian transmission of traits from mothers to their offspring. Despite its presence in virtually all organisms, acting through a variety of mechanisms, the evolutionary consequences of maternal inheritance are not well understood. Here we review and extend a model of the inheritance and evolution of multiple quantitative characters with complex pathways of maternal effects. Extensions of the earlier model include common family environmental effects not associated with maternal phenotype, sexual dimorphism, and paternal effects (non-Mendelian influence of the father on offspring traits). We find that, in contrast to simple Mendelian inheritance, maternal inheritance produces qualitatively different evolutionary dynamics for two reasons: (1) the response to selection on a set of characters depends not only on their additive genetic variances and covariances, but also on maternal characters that influence them, and (2) time lags in the response to selection create a form of evolutionary momentum. These results have important implications for evolution in natural populations and practical applications in the economic improvement of domesticated species. We derive selection indices that maximize either the economic improvement in a single generation of artificial selection or the asymptotic rate of improvement in long-term selection programmes, based on individual merit or a combination of individual and family merit. Numerical examples show that accounting for maternal inheritance can lead to considerable increases in the efficiency of artificial selection.
Analysis of the inheritance, selection and evolution of growth trajectories.
We present methods for estimating the parameters of inheritance and selection that appear in a quantitative genetic model for the evolution growth trajectories and other "infinite-dimensional" traits that we recently introduced. Two methods for estimating the additive genetic covariance function are developed, a "full" model that fully fits the data and a "reduced" model that generates a smoothed estimate consistent with the sampling errors in the data. By decomposing the covariance function into its eigenvalues and eigenfunctions, it is possible to identify potential evolutionary changes in the population's mean growth trajectory for which there is (and those for which there is not) genetic variation. Algorithms for estimating these quantities, their confidence intervals, and for testing hypotheses about them are developed. These techniques are illustrated by an analysis of early growth in mice. Compatible methods for estimating the selection gradient function acting on growth trajectories in natural or domesticated populations are presented. We show how the estimates for the additive genetic covariance function and the selection gradient function can be used to predict the evolutionary change in a population's mean growth trajectory.
Thoughts about the origins of femininity.
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Genetic segregation and the maintenance of sexual reproduction.
Sexual reproduction confronts evolutionary biology with a paradox: other things being equal, an asexual (all-female) population will have twice the reproductive potential of a competing sexual population and therefore should rapidly drive the sexual population to extinction. Thus, the persistence of sexual reproduction in most life forms implies a compensatory advantage to sexual reproduction. Work on this problem has emphasized the evolutionary advantages produced by the genetic recombination that accompanies sexual reproduction. Here we show that genetic segregation produces an advantage to sexual reproduction even in the absence of an advantage from recombination. Segregation in a diploid sexual population allows selection to carry a single advantageous mutation to a homozygous state, whereas two separate mutations are required in a parthenogenetic population. The complete fixation of advantageous mutations is thus delayed in a heterozygous state in asexual populations. Calculation of the selective load incurred suggests that it may offset the intrinsic twofold reproductive advantage of asexual reproduction and maintain sexual reproduction in diploid populations.
Sexual selection. Is bigger always better?
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A quantitative genetic model for growth, shape, reaction norms, and other infinite-dimensional characters.
Infinite-dimensional characters are those in which the phenotype of an individual is described by a function, rather than by a finite set of measurements. Examples include growth trajectories, morphological shapes, and norms of reaction. Methods are presented here that allow individual phenotypes, population means, and patterns of variance and covariance to be quantified for infinite-dimensional characters. A quantitative-genetic model is developed, and the recursion equation for the evolution of the population mean phenotype of an infinite-dimensional character is derived. The infinite-dimensional method offers three advantages over conventional finite-dimensional methods when applied to this kind of trait: (1) it describes the trait at all points rather than at a finite number of landmarks, (2) it eliminates errors in predicting the evolutionary response to selection made by conventional methods because they neglect the effects of selection on some parts of the trait, and (3) it estimates parameters of interest more efficiently.
Symptoms and signs of progressive hydrocephalus.
The clinical features of 107 cases of children with hydrocephalus and measured raised intraventricular pressure were analysed retrospectively. Fifty one children had recently been diagnosed as having hydrocephalus, and the remainder had had shunts injected to direct the cerebrospinal fluid. The most common symptoms in the group were vomiting, behavioural changes, drowsiness, and headaches. The most common clinical signs were inappropriately increasing occipitofrontal head circumferences, tense anterior fontanelles, splayed sutures, and distension of the scalp veins. Half the infantile cases of hydrocephalus were without symptoms, and a quarter of the cases with cerebrospinal fluid shunts and measured raised intraventricular pressure were without signs. There were no fewer than 33 different clinical signs including several unusual ones, such as macular rash and sweating. We believe that the presentation of hydrocephalus with raised intraventricular pressure is sufficiently variable, unusual, or even absent to justify the direct measurement of intracranial pressure.
The evolution of growth trajectories and other complex quantitative characters.
Growth trajectories differ from many other quantitative characters in that they are characterized by a continuous function rather than by a finite number of discrete measurements. We review here recently developed methods for predicting the evolution of growth trajectories under the influence of natural or artificial selection. Using our method, analysis of genetic data from mice shows that the patterns of genetic variation arising from developmental processes impose constraints on evolution of growth trajectories. These constraints can be quantified to reveal the families of growth trajectories that can be produced by selection and those families that cannot. The data suggest there may be relatively few evolutionary degrees of freedom for growth trajectories despite the presence of abundant additive genetic variation to alter size and (or) growth rate at every age. The description of these constraints may be useful to both biologists who would like to determine the evolutionary options available to natural populations and to breeders who would like to alter growth trajectories to economically improve domesticated species. Our methods and conclusions can be generalized to other kinds of "infinite-dimensional" or complex characters, including morphological shapes and norms of reaction.
Management of dysentery by community health workers.
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Treatment of requests for sex-change surgery with psychotherapy.
The authors describe two patients whose requests for sex-change surgery represented crises in sexual identity and anxiety-masking symptoms. Brief psychotherapy enabled these patients to relinquish their belief in a surgical "cure". In evaluating such request, the psychiatrist should consider the patient's total personality rather than focusing on the genuineness of the perceived gender disorder. Whatever the final decision, the opportunity for continued psychotherapy should be provided.
Evaluation of a new single-use thermometer.
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Changing attitudes of disabled females through assertiveness training.
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