Chris Cannings

Bio: Chris Cannings is an academic researcher from University of Sheffield. The author has contributed to research in topics: Population & Evolutionarily stable strategy. The author has an hindex of 28, co-authored 104 publications receiving 4393 citations. Previous affiliations of Chris Cannings include University of Pavia & University of Cambridge.

Handbook of statistical genetics

Abstract: Editors' Preface. List of Contributors. BIOINFORMATICS. Chromosome Maps (T. Speed and H. Zhao). Statistical Significance in Biological Sequence Comparison (W. Pearson and T. Wood). Probabilistic Models for the Study of Protein Evolution (J. Thorne and N. Goldman). Statistical Approaches in Eukaryotic Gene Prediction (V. Solovyev). Protein Structure (W. Taylor). POPULATION GENETICS. Mathematical Models in Population Genetics (C. Neuhauser). Coalescent Theory (M. Nordborg). Inference Under the Coalescent (M. Stephens). Inferences from Spatial Population Genetics (F. Rousset). Analysis of Population Subdivision (L. Excoffier). Linkage Disequilibrium and Recombination (R. Hudson) EVOLUTIONARY GENETICS. Adaptive Molecular Evolution (Z. Yang). Genome Evolution (J. Brookfield). Virus Evolution (Y. Suzuki, et al.). Application of the Likelihood Function in Phylogenetic Analysis (J. Huelsenbeck and J. Bollback). Phylogenetics: Parsimony and Distance Methods (D. Penny and M. Hendy). GENETIC EPIDEMIOLOGY. Nonparametric Linkage (P. Holmans). The Transmission/Disequilibrium Test (W. Ewens and R. Spielman). Population Association (D. Clayton). Linkage Analysis (E. Thompson). ANIMAL AND PLANT GENETICS. Quantitative Trait Loci in Inbred Lines (R. Jansen). Mapping Quantitative Trait Loci in Outbred Pedigrees (I. Hoeschele). Inferences About Breeding Values (D. Gianola). Marker-Assisted Selection and Introgression (J. Whittaker). APPLICATIONS. Ethics in the Use of Statistics in Genetics (D. Beyleveld). Forensics (B. Weir). Pharmacogenetics (N. Schork, et al.). Statistical Basis of Risk Calculations (R. Chakraborty). Conservation Genetics (M. Beaumont). Genetic History of the Human Species (J. Relethford). Index

Probability functions on complex pedigrees

Abstract: The calculation of probabilities on pedigrees of arbitrary complexity is discussed for a basic model of transmission and penetrance (encompassing Mendelian inheritance, and certain environmental influences). The structure of pedigrees, and the types of loops occurring, is discussed. Some results in graph theory are obtained and, using these, a recurrence relation derived for certain probabilities. The recursive procedure enables the successive peeling off of certain members of the pedigree, and the condensation of the information on those individuals into a function on a subset of those remaining. The underlying theory is set out, and examples given of the utilization of the resulting algorithm.

Single nucleotide polymorphisms in the human interleukin-1B gene affect transcription according to haplotype context

Abstract: We questioned the significance of haplotype structure in gene regulation by testing whether individual single nucleotide polymorphisms (SNPs) within a gene promoter region [interleukin-1-beta (IL1B)] might affect promoter function and, if so, whether function was dependent on haplotype context. We sequenced genomic DNA from 25 individuals of diverse ethnicity, focusing on exons and upstream flanking regions of genes of the cluster. We identified four IL1B promoter region SNPs that were active in transient transfection reporter gene assays. To substantiate allelic differences found in reporter gene assays, we also examined nuclear protein binding to promoter sequence oligonucleotides containing different alleles of the SNPs. The effect of individual SNPs on reporter gene transcription varied according to which alleles of the three other SNPs were present in the promoter construct. The SNP patterns that influenced function reflected common haplotypes that occur in the population, suggesting functionally significant interactions between SNPs according to haplotype context. Of the haplotypes that include the four functional IL1B promoter SNPs (-3737, -1464, -511, -31), the four haplotypes that showed different contextual effects on SNP function accounted for >98% of the estimated haplotypes in Caucasian and African-American populations. This finding underlines the importance of understanding the haplotype structure of populations used for genetic studies and may be especially important in the functional analysis of genetic variation across gene regulatory regions.

The latent roots of certain Markov chains arising in genetics: A new approach, I. Haploid models

Abstract: Haploid models of genetic drift in populations of constant size are considered. Generalizations of the models of Moran and Wright have been developed by Karlin and McGregor (for multiple alleles and non-overlapping generations), by Chia and Watterson (for two alleles and overlapping or non-overlapping generations) and by Chia (for multiple alleles and overlapping or non-overlapping generations), using conditioned branching processes. A new approach is developed which contains the models mentioned above and provides simpler expressions for the latent roots. A greater dependence between the birth events and death events can be permitted, and non-independent mutations treated.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.

Construction of a genetic linkage map in man using restriction fragment length polymorphisms.

Abstract: We describe a new basis for the construction of a genetic linkage map of the human genome. The basic principle of the mapping scheme is to develop, by recombinant DNA techniques, random single-copy DNA probes capable of detecting DNA sequence polymorphisms, when hybridized to restriction digests of an individual's DNA. Each of these probes will define a locus. Loci can be expanded or contracted to include more or less polymorphism by further application of recombinant DNA technology. Suitably polymorphic loci can be tested for linkage relationships in human pedigrees by established methods; and loci can be arranged into linkage groups to form a true genetic map of "DNA marker loci." Pedigrees in which inherited traits are known to be segregating can then be analyzed, making possible the mapping of the gene(s) responsible for the trait with respect to the DNA marker loci, without requiring direct access to a specified gene's DNA. For inherited diseases mapped in this way, linked DNA marker loci can be used predictively for genetic counseling.

Random graphs

Abstract: We will review some of the major results in random graphs and some of the more challenging open problems. We will cover algorithmic and structural questions. We will touch on newer models, including those related to the WWW.