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Biomedical subjects

Chris Cannings

Publications and source records attributed to Chris Cannings.

10 recordsLinked to original sources
PubMed2006

Estimating the parameters of a model for protein-protein interaction graphs.

We find accurate approximations for the expected number of three-cycles and unchorded four-cycles under a stochastic distribution for graphs that has been proposed for modelling yeast two-hybrid protein-protein interaction networks. We show that unchorded four-cycles are characteristic motifs under this model and that the count of unchorded four-cycles in the graph is a reliable statistic on which to base parameter estimation. Finally, we test our model against a range of experimental data, obtain parameter estimates from these data and investigate possible improvements in the model. Characterization of this model lays the foundation for its use as a prior distribution in a Bayesian analysis of yeast two-hybrid networks that can potentially aid in identifying false-positive and false-negative results.

Algorithms↗
PubMed2005

The probability density of the total IBD length over a single autosome in unilineal relationships.

Several authors have studied identity by descent (IBD) by way of a continuous recombination process along a chromosome. Despite its potential uses in, for example, gene mapping or delineation of biological relationships there has been no exact algebraic result given for the probability density function of the IBD proportion in any familial relationship. Other authors have derived algebraic approximations in the case of half-sibs by way of the Poisson clumping heuristic and used computational methods to compute the distribution function of the IBD sharing for unilineal relationships. Here we provide a general numerical method for finding the density of IBD sharing that could be applied to any unilineal relationship and more importantly we derive algebraically an expression for the density for a grandparent-grandchild relationship. Initially we assume that recombination events occur at random along a chromosome, then go on to show how the method could be extended to incorporate a form of genetic interference.

Crossing Over, Genetic↗
PubMed2004

Sequential genotyping within TDT families.

We demonstrate that, given a limited amount of genotyping resources, the power of a TDT study can be increased substantially by genotyping within families sequentially. By sequential genotyping we mean that one parent in a family should be typed and then the decision on whether to continue genotyping the family is based on this parent's genotype. If it is decided to continue genotyping then a further decision is made about whether to genotype the offspring once the second parent has been genotyped. We show that, for a given power, reductions in sample size of over 80% are possible, even for the most robust selection strategies. We discuss the practical application of such sequential genotyping and illustrate its potential using a real data set.

Child↗
PubMed2004

Simulating realistic zero loop pedigrees using a bipartite Prufer code and graphical modelling.

Graph algorithms previously developed by the authors are adapted to simulate pedigrees similar to those used in genetic linkage studies which associate disease phenotypes with specific genomic locations. Pedigrees are chosen uniformly at random from the set of those with specified numbers of individuals and matings and which contain no loops. Summary statistics from pedigrees generated in this way can be used to check real pedigrees for anomalies due to biased sampling or phenotypic effects on the pedigree structure.

Algorithms↗
PubMed2003

Patch leaving strategies and superparasitism: an asymmetric generalized war of attrition.

When several competitors deplete a patch, it can be advantageous for each of them to stay provided that others leave, whereas, on the other hand, staying longer decreases the expected payoff for everyone. This situation can be considered as a generalized war of attrition. Previous studies have shown that optimal patch leaving strategies become stochastic and the expected leaving time is much larger than predicted by the marginal value theorem when competitors interfere. The possibility of superparasitism, as occurs for example in parasitoids, induces such interference. In addition, it gives several complications. First, the payoff of females that have left the patch is affected by the ovipositions of the remaining individuals. Second, differences in the arrival time of females cause payoff-relevant asymmetries, since females that arrived early on have parasitized more hosts in a patch at the moment superparasitism starts than those that arrived later. We show that this can be modelled as an asymmetric generalized war of attrition, and derive global characteristics of the ESS for simultaneous decisions on when to start superparasitism and when to leave a patch.

Animals↗
PubMed2003

Variation within genes encoding interleukin-1 and the interleukin-1 receptor antagonist influence the severity of meningococcal disease.

BACKGROUND: Genetically determined variation in proinflammatory cytokine release influences severity of meningococcal disease and other serious infections. OBJECTIVE: To ascertain the relative frequencies of single nucleotide polymorphisms within the interleukin-1 gene locus among patients who survived and those who died of meningococcal disease and a control population of blood donors. DESIGN: Association study. SETTING: England and Wales. PATIENTS: 1106 consecutively received blood samples from persons with microbiologically confirmed meningococcal disease and 839 samples from blood donors. MEASUREMENTS: Patient demographic and outcome data, infecting meningococcal serogroups, and genotype at the IL1B(-511) and IL1RN(+2018) loci of patients and blood donor controls. RESULTS: Genotype frequency did not differ between patients with meningococcal disease and blood donor controls. Logistic regression analysis revealed that the likelihood of death was significantly influenced by age but not socioeconomic status and was higher in patients who were infected with serogroup C (odds ratio for survival, 0.50 [95% CI, 0.33 to 0.78]). Patients carrying the common allele at IL1B(-511) were more likely to survive (odds ratio, 2.01 [CI, 1.11 to 3.79]). Patients with this allele were less likely to survive if they also carried the rare allele at IL1RN(+2018) (odds ratio, 0.61 [CI, 0.38 to 0.993]). CONCLUSION: Genotype at the interleukin-1 gene locus influences likelihood of survival of meningococcal disease but has no effect on susceptibility to the infection. Increasing age and infection with serogroup C also influence the likelihood of death.

Adolescent↗
PubMed2003

Recombination can evolve in large finite populations given selection on sufficient loci.

It is well known that an allele causing increased recombination is expected to proliferate as a result of genetic drift in a finite population undergoing selection, without requiring other mechanisms. This is supported by recent simulations apparently demonstrating that, in small populations, drift is more important than epistasis in increasing recombination, with this effect disappearing in larger finite populations. However, recent experimental evidence finds a greater advantage for recombination in larger populations. These results are reconciled by demonstrating through simulation without epistasis that for m loci recombination has an appreciable selective advantage over a range of population sizes (am, bm). bm increases steadily with m while am remains fairly static. Thus, however large the finite population, if selection acts on sufficiently many loci, an allele that increases recombination is selected for. We show that as selection acts on our finite population, recombination increases the variance in expected log fitness, causing indirect selection on a recombination-modifying locus. This effect is enhanced in those populations with more loci because the variance in phenotypic fitnesses in relation to the possible range will be smaller. Thus fixation of a particular haplotype is less likely to occur, increasing the advantage of recombination.

Alleles↗
PubMed2003

Enumeration and simulation of marriage node graphs on zero-loop pedigrees.

We present a method that for the marriage node graph of a zero-loop pedigree will enumerate all possible pedigrees that share the same underlying tree structure. The enumeration method leads naturally to a scheme for simulating from a uniform distribution on such pedigrees. This is extended to simulating pedigrees for which the underlying marriage node graph is a tree of any particular size.

Female↗
PubMed2003

The identity by descent process along the chromosome.

The probabilities of the various possible identity by descent (IBD) states at a locus captures all the genealogical information for that locus for the set of individuals under consideration. Here we study the stochastic process of the IBD state as one moves across the genome of a set of individuals. In general it is no longer sufficient to specify the IBD state, one needs to increase the state space if one is to maintain the Markov property, as has been discussed by for instance McPeak and Sun [Am J Hum Genet 2000;66:1076-1094] and Browning and Browning [Theor Popul Biol 2002;62:1-8]. This paper discusses a general method of deriving the transition matrix for that Markov chain iteratively from one time point to a subsequent one. This method allows a considerable reduction in the size of the state space needed. The basic recursion is set out here and the application is illustrated by two specific examples.

Alleles↗