Publications

Bovine mastitis remains the most common and costly disease of dairy cattle worldwide. A complementary control measure to herd hygiene and vaccine development would be to selectively breed cattle with greater resistance to mammary infection. Toll-like receptor 1 (TLR1) has an integral role for the initiation and regulation of the immune response to microbial pathogens, and has been linked to numerous inflammatory diseases. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) within the bovine TLR1 gene (boTLR1) are associated with clinical mastitis (CM). Selected boTLR1 SNPs were analysed within a Holstein Friesian herd. Significant associations were found for the tagging SNP -79 T > G and the 3'UTR SNP + 2463 C > T. We observed favourable linkage of reduced CM with increased milk fat and protein, indicating selection for these markers would not be detrimental to milk quality. Furthermore, we present evidence that some of these boTLR1 SNPs underpin functional variation in bovine TLR1. Animals with the GG genotype (from the tag SNP -79 T > G) had significantly lower boTLR1 expression in milk somatic cells when compared with TT or TG animals. In addition, stimulation of leucocytes from GG animals with the TLR1-ligand Pam3csk4 resulted in significantly lower levels of CXCL8 mRNA and protein. SNPs in boTLR1 were significantly associated with CM. In addition we have identified a bovine population with impaired boTLR1 expression and function. This may have additional implications for animal health and warrants further investigation to determine the suitability of identified SNPs as markers for disease susceptibility.

Truck trap collections of Culicoides biting midges (Diptera: Ceratopogonidae) were made during 2 yr of sampling from 2008 to 2009 at a farm site in southern England. Samples were collected from 810 sample runs carried out over 52 d and contained 7,095 Culicoides of which more than half (50.3%) were identified as Culicoides obsoletus Meigen by using a multiplex polymerase chain reaction assay. Other commonly encountered species included Culicoides scoticus Downes & Kettle (14.7% of total Culicoides caught), Culicoides dewulfi Goetghebuer (3.7%), and Culicoides chiopterus Meigen (4.2%). The activity rates of these species were examined with regard to both meteorological factors (light intensity, humidity, temperature, and wind speed and direction) and other potentially contributing variables (lunar phase and brightness, sunset time, and year) by using generalized linear models. All the species examined were collected in greater abundance at sunset, although the relationship between underlying light intensity and numbers was less pronounced in C. dewulfi and C. chiopterus. Collections of Culicoides were reduced at temperatures above 21 degrees C and were inversely related to wind speed. Variation between species was recorded, however, in response to wind direction: C. dewulfi and C. chiopterus were associated with prevailing winds passing through fields containing livestock, whereas C. obsoletus and C. scoticus demonstrated no such relationship. A male: female ratio of 1: 3.56 was observed in catches, and male populations were protandrous. These results are discussed with reference both to the ecology of these species and methods currently used to predict adult Culicoides movement and abundance in Europe.

Successful control of livestock diseases requires an understanding of how they spread amongst animals and between premises. Mathematical models can offer important insight into the dynamics of disease, especially when built upon experimental and/or field data. Here the dynamics of a range of epidemiological models are explored in order to determine which models perform best in capturing real-world heterogeneities at sufficient resolution. individual based network models are considered together with one- and two-class compartmental models, for which the final epidemic size is calculated as a function of the probability of disease transmission occurring during a given physical contact between two individuals. For numerical results the special cases of a viral disease with a fast recovery rate (foot-and-mouth disease) and a bacterial disease with a slow recovery rate (brucellosis) amongst sheep are considered. Quantitative results from observational studies of physical contact amongst domestic sheep are applied and results from the differently structured flocks (ewes with newborn lambs, ewes with nearly weaned lambs and ewes only) compared. These indicate that the breeding cycle leads to significant changes in the expected basic reproduction ratio of diseases. The observed heterogeneity of contacts amongst animals is best captured by full network simulations, although simple compartmental models describe the key features of an outbreak but, as expected, often overestimate the speed of an outbreak. Here the weights of contacts are heterogeneous, with many low weight links. However, due to the well-connected nature of the networks, this has little effect and differences between models remain small. These results indicate that simple compartmental models can be a useful tool for modelling real-world flocks; their applicability will be greater still for more homogeneously mixed livestock, which could be promoted by higher intensity farming practices.

Immunoglobulin (IG) gene rearrangement and expression are central to disease resistance and health maintenance in animals. The IG kappa (IGK) locus in swine (Sus scrofa domestica) contributes to approximately half of all antibody molecules, in contrast to many other Cetartiodactyla, whose members provide the majority of human dietary protein and in which kappa locus utilization is limited. The porcine IGK variable locus is 27.9 kb upstream of five IG kappa J genes (IGKJ) which are separated from a single constant gene (IGKC) by 2.8 kb. Fourteen variable genes (IGKV) were identified, of which nine are functional and two are open reading frame (ORF). Of the three pseudogenes, IGKV3-1 contains a frameshift and multiple stop codons, IGKV7-2 contains multiple stop codons, and IGKV2-5 is missing exon 2. The nine functional IGKV genes are phylogenetically related to either the human IGKV1 or IGKV2 subgroups. IGKV2 subgroup genes were found to be dominantly expressed. Polymorphisms were identified on overlapping BACs derived from the same individual such that 11 genes contain amino acid differences. The most striking allelic differences are present in IGKV2 genes, which contain as many as 16 amino acid changes between alleles, the majority of which are in complementarity determining region (CDR) 1. In addition, many IGKV2 CDR1 are shared between genes but not between alleles, suggesting extensive diversification of this locus through gene conversion.