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Biomedical subjects

M Kirkpatrick

Publications and source records attributed to M Kirkpatrick.

At least 19 recordsLinked to original sources
PubMed2000

CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the beta2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE.

Acetylcholine↗
PubMed2000

Inbreeding depression due to mildly deleterious mutations in finite populations: size does matter.

We studied the effects of population size on the inbreeding depression and genetic load caused by deleterious mutations at a single locus. Analysis shows how the inbreeding depression decreases as population size becomes smaller and/or the rate of inbreeding increases. This pattern contrasts with that for the load, which increases as population size becomes smaller but decreases as inbreeding rate goes up. The depression and load both approach asymptotic limits when the population size becomes very large or very small. Numerical results show that the transition between the small and the large population regimes is quite rapid, and occurs largely over a range of population sizes that vary by a factor of 10. The effects of drift on inbreeding depression may bias some estimates of the genomic rate of deleterious mutation. These effects could also be important in the evolution of breeding systems in hermaphroditic organisms and in the conservation of endangered populations.

Genetics, Population↗
PubMed2000

Runaway sexual selection when female preferences are directly selected.

We introduce models for the runaway coevolution of female mating preferences and male display traits. The models generalize earlier results by allowing for direct natural selection on the preference, arbitrary forms of mate choice, and fairly general assumptions about the underlying genetics. Results show that a runaway is less likely when there is direct selection on the preference, but that it is still possible if there is a sufficiently large phenotypic correlation between the female's preference and the male's trait among mated pairs. Comparison of three preference functions introduced by Lande (1981) shows that open-ended preferences are particularly prone to a runaway, and that absolute preferences require very large differences between females in their preferences. We analyze the causes of the runaway seen in a model developed by Iwasa and Pomiankowski (1995).

Animals↗
PubMed1999

The variability of force platform data in normal and cerebral palsy gait.

OBJECTIVE: To determine the natural variability and symmetry of force platform parameters in normal and cerebral palsy gait. DESIGN: Force platform data has been analysed using coefficient of variation, analysis of variances and symmetry index. BACKGROUND: It is important to establish the natural variability of force platform data so that changes in gait due to natural variability and those due to intervention can be determined. METHODS: Force platform data and walking speed were recorded in 15 normal volunteers and 11 children with cerebral palsy on 3 consecutive days. Five recordings were made of each leg on each day. RESULTS: The force platform parameters in both groups showed greater asymmetry in the horizontal plane. In the cerebral palsy group significant asymmetry was found in all 3 directions. The variation of the vertical ground reaction force peaks (Fz1 and Fz3) and of the anterior-posterior negative peak (Fy3) for both groups was low. Fz3 was the most reproducible force parameter. The other force parameters showed high variability and are not considered reliable measures of gait. The temporal parameters and the walking speed were reproducible measures. CONCLUSIONS: Only selected ground reaction force parameters showed acceptable stability and reproducibility. Therefore caution has to be taken in the selection of these parameters, when assessing the effects of any intervention on cerebral palsy gait.

Adult↗
PubMed1999

Artificial selection on phenotypically plastic traits.

Many phenotypes respond physiologically or developmentally to continuously distributed environmental variables such as temperature and nutritional quality. Information about phenotypic plasticity can be used to improve the efficiency of artificial selection. Here we show that the quantitative genetic theory for 'infinite-dimensional' traits such as reaction norms provides a natural framework to accomplish this goal. It is expected to improve selection responses by making more efficient use of information about environmental effects than do conventional methods. The approach is illustrated by deriving an index for mass selection of a phenotypically plastic trait. We suggest that the same approach could be extended directly to more general and efficient breeding schemes, such as those based on general best linear unbiased prediction. Methods for estimating genetic covariance functions are reviewed.

Animals↗
PubMed1999

The reinforcement of mating preferences on an island.

We develop a haploid model for the reinforcement of female mating preferences on an island that receives migrants from a continent. We find that preferences will evolve to favor island males under a broad range of conditions: when the average male display trait on the island and continent differ, when the preference acts on that difference, and when there is standing genetic variance for the preference. A difference between the mean display trait on the continent and on the island is sufficient to drive reinforcement of preferences. Additional postzygotic isolation, caused, for example, by either epistatic incompatibility or ecological selection against hybrids, will amplify reinforcement but is not necessary. Under some conditions, the degree of preference reinforcement is a simple function of quantities that can be estimated entirely from phenotypic data. We go on to study how postzygotic isolation caused by epistatic incompatibilities affects reinforcement of the preference. With only one pair of epistatic loci, reinforcement is enhanced by tighter linkage between the preference genes and the genes causing hybrid incompatibility. Reinforcement of the preference is also affected by the number of epistatically interacting genes involved in incompatibility, independent of the overall intensity of selection against hybrids.

Animals↗
PubMed1997

The strength of indirect selection on female mating preferences.

An important but controversial class of hypotheses concerning the evolution of female preferences for extreme male mating displays involves "indirect selection." Even in the absence of direct fitness effects, preference for males with high overall fitness can spread via a genetic correlation that develops between preference alleles and high fitness genotypes. Here we develop a quantitative expression for the force of indirect selection that (i) applies to any female mating behavior, (ii) is relatively insensitive to the underlying genetics, and (iii) is based on measurable quantities. In conjunction with the limited data now available, it suggests that the evolutionary force generated by indirect selection on preferences is weak in absolute terms. This finding raises the possibility that direct selection on preference genes may often be more important than indirect selection, but more data on the quantities identified by our model and on direct selection are needed to decide the question.

Animals↗
PubMed1994

Spinal cord dysfunction in neonatal meningococcal meningitis.

A 3-week-old infant with meningococcal meningitis is described whose clinical course was complicated by paraparesis and urinary retention. This rare complication of meningococcal meningitis has not previously been reported in the neonatal age group.

Female↗
PubMed1994

Estimating the covariance structure of traits during growth and ageing, illustrated with lactation in dairy cattle.

Quantitative variation in traits that change with age is important to both evolutionary biologists and breeders. We present three new methods for estimating the phenotypic and additive genetic covariance functions of a trait that changes with age, and illustrate them using data on daily lactation records from British Holstein-Friesian dairy cattle. First, a new technique is developed to fit a continuous covariance function to a covariance matrix. Secondly, this technique is used to estimate and correct for a bias that inflates estimates of phenotypic variances. Thirdly, we offer a numerical method for estimating the eigenvalues and eigenfunctions of covariance functions. Although the algorithms are moderately complex, they have been implemented in a software package that is made freely available. Analysis of lactation shows the advantages of the new methods over earlier ones. Results suggest that phenotypic variances are inflated by as much as 39% above the underlying covariance structure by measurement error and short term environmental effects. Analysis of additive genetic variation indicates that about 90% of the additive genetic variation for lactation during the first 10 months is associated with an eigen-function that corresponds to increased (or decreased) production at all ages. Genetic tradeoffs between early and late milk yield are seen in the second eigen-function, but it accounts for less than 8% of the additive variance. This illustrates that selection is expected to increase production throughout lactation.

Aging↗
PubMed1993

Preliminary evaluation of Cyto-Rich: an improved automated cytology preparation.

A new cervical cytology monolayer preparation system called Cyto-Rich was evaluated. Using samples from 557 patients, Cyto-Rich monolayers were compared to matched conventional smears. After conventional smears were prepared and spray fixed, residual exfoliated cells were transferred to preservative fluid. The cell suspensions were gently disaggregated and the epithelial component enriched with gradient centrifugal sedimentation. The batched samples were then placed on the Cyto-Rich work station where slides are automatically prepared and stained. The results demonstrate that Cyto-Rich prepared monolayers are vastly superior to the conventional smears for cell presentation. While the study showed 99% overall concordance. Cyto-Rich improved the detection of low-grade cervical intraepithelial lesions.

Automation↗