Polymorphisms in the selectin gene cluster are associated with fertility and survival time in a population of Holstein Friesian cows

Selectins are adhesion molecules, which mediate attachment between leucocytes and endothelium. They aid extravasation of leucocytes from blood into inflamed tissue during the mammary gland’s response to infection. Selectins are also involved in attachment of the conceptus to the endometrium and subsequent placental development. Poor fertility and udder health are major causes for culling dairy cows. The three identified bovine selectin genes SELP, SELL and SELE are located in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in SELP and SELE are associated with human vascular disease, while SELP SNP rs6127 has been associated with recurrent pregnancy loss in women. This study describes the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and SELE (n = 1) with fertility, milk production and longevity traits in a population of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at 6 months of age and animals were monitored until either culling or 2,340 days from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala substitution at rs42312260. This region was associated with poor fertility and reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus in the linking region between consensus repeats 4 and 5, which may influence glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA homozygotes present in the population and AG heterozygotes had significantly worse fertility than GG homozygotes. Small changes in milk production associated with some SNP could not account for the reduced fertility and only SELPEx6 showed any association with somatic cell count. These results suggest that polymorphisms in SELP and SELE are associated with the likelihood of successful pregnancy, potentially through compromised implantation and placental development

Association of bovine leptin polymorphisms with energy output and energy storage traits in progeny tested Holstein-Friesian dairy cattle sires

peer-reviewedBackground: Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. Results: All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P < 0.05) with milk protein concentration and calf perinatal mortality. It had a tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was associated (P < 0.05) with reduced milk fat concentration, reduced milk protein concentration, longer gestation length and tended to associate (P < 0.1) with an increase in calving difficulty, calf perinatal mortality and somatic cells in the milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and gestation length. It also tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and length of gestation. The T allele of the Y7F SNP significantly associated with reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There was also a tendency (P < 0.1) for Y7F to associate with increased body condition score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with reduced survival in the herd (P < 0.05). Conclusions Several leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow.Department of Agriculture, Food and Fisheries, Ireland - Research Stimulus Fund (RSF-06-0353; RSF-06-0409); Irish Dairy Research Trust; Teagasc Walsh Fellowshi

Rare Variants in APP, PSEN1 and PSEN2 Increase Risk for AD in Late-Onset Alzheimer's Disease Families

Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD). Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7%) carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN) three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09×10−5; OR = 2.21; 95%CI = 1.49–3.28) or an unselected population of 12,481 samples (p = 6.82×10−5; OR = 2.19; 95%CI = 1.347–3.26). Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS

The impact of early life nutrition and housing on growth and reproduction in dairy cattle

Contentious issues in calf rearing include milk feeding practices and single versus group housing. The current study was performed on a high producing 170 Holstein cow dairy farm, to investigate the impact of nutrition and housing on growth and reproduction. Heifer calves (n = 100) were allocated in birth order to one of two commonly used management strategies. All calves received 3-4 litres of dam specific colostrum within 6 hours of birth. Group A calves were group housed from birth and fed milk replacer (MR) ad libitum via a computerised machine utilising a single teat, with weaning commencing at 63 days of age. Group R calves were initially housed in individual pens and received 2.5 litres of MR twice daily via a bucket until 21 days of age when they were group housed and fed 3 litres of MR twice daily via a group trough with weaning commencing at 56 days. From 12 weeks of age onwards, calves in both dietary groups were subject to common nutritional and husbandry protocols. All breeding of heifers was via artificial insemination with no hormonal intervention. Calves were weighed, body condition scored and morphometric measures recorded weekly up till 12 weeks of age then monthly until conception. Pre-weaning growth rates (kg/day) were significantly higher in Group A calves compared to Group R (0.89, 95% CI 0.86-0.93 vs 0.57, 95% CI 0.54-0.6 kg/day P 0.050) in any of the mean values of measured reproductive parameters, multivariable Cox regression suggested that there was a weak trend (P = 0.072) for Group A animals to achieve first service earlier than their Group R counterparts (62.6 weeks versus 65.3 weeks). Irrespective of dietary group, the hazard for achievement of all measured reproductive parameters, apart from time to puberty, was 20-40% less for heifers borne from multiparous dams compared to heifers from primiparous dams

Suboptimal herd performance amplifies the spread of infectious disease in the cattle industry

Farms that purchase replacement breeding cattle are at increased risk of introducing many economically important diseases. The objectives of this analysis were to determine whether the total number of replacement breeding cattle purchased by individual farms could be reduced by improving herd performance and to quantify the effects of such reductions on the industry-level transmission dynamics of infectious cattle diseases. Detailed information on the performance and contact patterns of British cattle herds was extracted from the national cattle movement database as a case example. Approximately 69% of beef herds and 59% of dairy herds with an average of at least 20 recorded calvings per year purchased at least one replacement breeding animal. Results from zero-inflated negative binomial regression models revealed that herds with high average ages at first calving, prolonged calving intervals, abnormally high or low culling rates, and high calf mortality rates were generally more likely to be open herds and to purchase greater numbers of replacement breeding cattle. If all herds achieved the same level of performance as the top 20% of herds, the total number of replacement beef and dairy cattle purchased could be reduced by an estimated 34% and 51%, respectively. Although these purchases accounted for only 13% of between-herd contacts in the industry trade network, they were found to have a disproportionately strong influence on disease transmission dynamics. These findings suggest that targeting extension services at herds with suboptimal performance may be an effective strategy for controlling endemic cattle diseases while simultaneously improving industry productivity

Optimising early youngstock management

The period from birth to first calving for a dairy heifer has not always received much attention on dairy farms, but success in this non-productive period is key to ensuring a profitable system of replacements. For calving at the optimum time of 24 months, growth must be on target and disease incidence must be minimised. This article covers aspects of management that influence growth and disease in this period; starting with colostrum management and success of passive transfer, then feeding of milk and other requirements pre-weaning, optimum housing for disease prevention, through to timing of first service. It is also crucial to record, monitor and assess the success of this period, and practical and applicable methods to do this on farm are discussed