Using regulatory variants to detect gene-gene interactions identifies networks of genes linked to cell immortalisation.

The extent to which the impact of regulatory genetic variants may depend on other factors, such as the expression levels of upstream transcription factors, remains poorly understood. Here we report a framework in which regulatory variants are first aggregated into sets, and using these as estimates of the total cis-genetic effects on a gene we model their non-additive interactions with the expression of other genes in the genome. Using 1220 lymphoblastoid cell lines across platforms and independent datasets we identify 74 genes where the impact of their regulatory variant-set is linked to the expression levels of networks of distal genes. We show that these networks are predominantly associated with tumourigenesis pathways, through which immortalised cells are able to rapidly proliferate. We consequently present an approach to define gene interaction networks underlying important cellular pathways such as cell immortalisation.

Cumulative incidence and risk factors for limber tail in the Dogslife labrador retriever cohort.

Limber tail is a condition that typically affects larger working breeds causing tail limpness and pain, resolving without veterinary intervention. It is poorly understood and the disease burden has not been well characterised. Data collected from owners of the Dogslife cohort of Labrador Retrievers have been used to describe incidents and a case-control study was undertaken to elucidate risk factors with 38 cases and 86 controls. The cumulative incidence of unexplained tail limpness was 9.7 per cent. Swimming is not a necessary precursor for limber tail, but it is a risk factor (OR=4.7) and working dogs were more susceptible than non-working dogs (OR=5.1). Higher latitudes were shown to be a risk factor for developing the condition and the case dogs were more related to each other than might be expected by chance. This suggests that dogs may have an underlying genetic predisposition to developing the condition. This study is the first, large-scale investigation of limber tail and the findings reveal an unexpectedly high illness burden. Anecdotally, accepted risk factors have been confirmed and the extent of their impact has been quantified. Identifying latitude and a potential underlying genetic predisposition suggests avenues for future work on this painful and distressing condition.

Dogslife: A cohort study of Labrador Retrievers in the UK.

Studies of animals that visit primary and secondary veterinary centres dominate companion animal epidemiology. Dogslife is a research initiative that collects data directly from owners about the health and lifestyle of Kennel Club (KC) registered Labrador Retrievers (LR) in the UK. The ultimate aim is to seek associations between canine lifestyle and health. A selection of data from Dogslife regarding the height, weight and lifestyle of 4307 LR up to four years of age is reported here. The majority of the dogs were household pets, living with at least one other pet, in families or households with more than one adult. The dogs typically ate diets of dried food and daily meal frequency decreased as the dogs aged. Working dogs spent more time exercising than pets, and dogs in Wales and Scotland were exercised more than their counterparts in England. Dogs in households with children spent less time exercising than dogs in other types of households. There was considerable variation in height and weight measurements indicative of a highly heterogeneous population. The average male height at the shoulders was 2-3cm taller than the UK breed standard. Dog weights continued to increase between one and four years of age. Those with chocolate coloured coats were heavier than their yellow and black counterparts. Greater dog weight was also associated with dogs whose owners reported restricting their dog's exercise due to where they lived. These findings highlight the utility of wide public engagement in the collation of phenotypic measures, providing a unique insight into the physical development and lifestyle of a cohort of LRs. In combination with concurrently collected data on the health of the cohort, phenotypic data from the Dogslife Project will contribute to understanding the relationship between dog lifestyle and health.

Protection of lambs against enteric colibacillosis by vaccination of ewes.

Pregnant ewes were vaccinated twice, seven weeks and three weeks before lambing, with a multivalent formalin-killed Escherichia coli vaccine containing an added K99, F41 antigen preparation. Lambs born to vaccinated and unvaccinated ewes were exposed to oral infection with E coli B44 (09:K30, K99, F41). All 10 lambs from vaccinated ewes were protected whereas all 10 control lambs developed severe diarrhoea and five died or were killed in extremis. In the following year, previously immunised ewes were given a single dose of the vaccine two weeks before lambing. Eleven of their 12 lambs were protected against a similar challenge, which caused the death of six of eight control lambs and severe diarrhoea in the two survivors. Higher levels of antibody to the K99, F41 preparation were detected by enzyme-linked immunosorbent assay in the serum and colostrum from vaccinated ewes and in the serum of their lambs when compared with similar samples from control ewes and lambs.

Surface temperature changes in response to handling in domestic chickens.

Stress-induced hyperthermia (SIH) occurs in numerous species and is characterised by an increase in core body temperature, and a decrease in surface temperature, of between 0.5 and 1.5°C within 10 to 15 min of the onset of "emotional stress". The aim of the current study was to ascertain whether the husbandry-relevant procedure of handling resulted in measurable changes in surface body temperature in chickens, as measured using infrared thermography. Baseline temperatures for 19 domestic hens were compared to temperatures immediately, and up to 20 min following handling (catching and brief restraint by a human). Surface head, eye and comb temperatures were plotted to investigate the pattern of temperature change. In response to handling, comb temperature decreased significantly, showing a rapid 2°C drop. Eye temperature showed an initial decrease then rose to levels significantly higher than handling. Head temperature increased over the 20 min post-handling period, to reach levels significantly higher than baseline. It can be concluded that surface temperature changes assessed using infrared thermography, in particular of the hen's comb, are sensitive to husbandry procedures such as handling and represent a potentially useful method for assessing stress-induced hyperthermia in chickens.