Vertebral and spinal dysplasia: A novel dominantly inherited congenital defect in Holstein cattle.

Monitoring and surveillance strategies are imperative for managing genetic defects in livestock populations in order to avoid detrimental effects on animal welfare and productivity. Recently, a number of previously unknown defects have been described in cattle, fostered by the huge progress in genome analysis and genomic selection. In response to reports about a potentially new defect in Holstein cattle, case-control studies were carried out to confirm a genetic background of the defect and to evaluate its phenotypic relevance. Eighty-five potentially affected offspring of a suspected carrier sire for the defect and 41 matched control calves were subjected to clinical and epidemiological monitoring on 39 farms. Forty-one animals, all offspring of the suspected carrier sire, showed pathognomonic tail malformations providing highly significant evidence for a congenital inherited defect, which was subsequently termed vertebral and spinal dysplasia (VSD). The defect is characterised by vertebral (specifically tail) deformities and neurological dysfunctions with gait abnormalities of the hind limbs. The deformities and neurological dysfunctions varied from very mild (only tail deformities) to severe (paraparesis). Detailed epidemiological monitoring provided no indication of environmental factors affecting VSD. The malformations and dysfunctions associated with VSD, as well as its mode of inheritance and the genotyping of the suspected carrier sire, indicated that VSD is a defect previously not described in cattle. VSD is inherited in a dominant mode, but shows incomplete penetrance of the phenotype, which impedes unequivocal identification of VSD carriers. A direct diagnostic genetic test for VSD is available.

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

BACKGROUND: Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. HYPOTHESIS: Dexamethasone treatment affects whole body insulin sensitivity. ANIMALS: Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. METHODS: Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 µg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. RESULTS: Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P < .001) concentrations, decreased SSGIR (HEC-II, P = .002; HEC-IV, P = .033), ISI (HEC-I, P < .015; HEC-II, P = .004), and insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Dexamethasone decreases whole body insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows.

Minimally-invasive catheterization of the portal, hepatic and cranial mesenteric veins and the abdominal aorta for quantitative determination of hepatic metabolism in dairy cows.

The objective of this study was to establish a minimally-invasive, ultrasound (US)-guided technique for the placement of indwelling catheters into the portal, hepatic, and cranial mesenteric veins as well as the abdominal aorta. Catheters were placed in eight healthy dairy cows on day 1. The patency of catheters was tested daily until day 14 when a necropsy was carried out. On day 6, energy intake and hepatic net output of glucose, removal of lactate, and oxygen were determined in seven cows. Post mortem examination revealed that all implanted catheters were in the intended locations. Loss of patency in one portal vein catheter on day 9 was attributable to a fibrin clot. Significant correlations were found between mean energy intake and mean hepatic plasma flow (r=0.91; P=0.004), hepatic glucose output (r=0.81; P=0.027) and hepatic removal of lactate (r=-0.70; P=0.08) and oxygen (r=-0.77; P=0.039), as well as between hepatic glucose net output and removal of lactate (r=-0.92; P=0.004). Minimally-invasive, US-guided transcutaneous catheter placement into the cranial mesenteric, portal and hepatic veins as well as the technique for catheterization of the abdominal aorta appear to be safe, and suitable for studies of quantitative hepatic metabolism in cattle.

The role of rare structural variants in the genetics of autism spectrum disorders.

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication and restricted interests and behaviors. Despite high estimates of heritability, genetic causes of ASD have long been elusive, due in part to a high degree of genetic and phenotypic heterogeneity (Bailey et al., 1995). Recently, important advances have been made in the genetics of ASD with the use of new technologies for the direct detection of copy number variation (CNV) in the human genome. CNV studies have revealed that de novo deletions and duplications, typically less than 1 Mb in size, are strongly associated with ASD, suggesting that spontaneous structural mutations play a more important role in the etiology of disease than was previously recognized. Rare mutations have been identified at many different locations in the genome, and multiple 'hot spots' have been identified where identical rearrangements recur with high frequency. These findings are consistent with the hypothesis that autism, like mental retardation, is caused by a large number of individually rare mutations. These studies serve as a model for how other emerging technologies for mutation detection (e.g. next generation sequencing platforms) could be used to further elucidate the role of rare sequence changes in ASD.