A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci

Performance and nutrient utilisation of dairy cows offered silages produced from three successive harvests of either a red clover–perennial ryegrass sward or a perennial ryegrass sward

The need to reduce reliance on imported protein feeds within the UK and Ireland has stimulated interest in locally grown forage legume crops, including red clover (Trifolium pratense L.). This 13-wk study examined the performance of 28 dairy cows offered silages produced from three successive harvests (H) of either a pure grass sward (GS) receiving 315 kg N/ha per annum or a red clover–perennial ryegrass sward (RCGS) receiving 22 kg N/ha per annum. The crops of H1, H2 and H3 were wilted for 48, 72 and 72 h, respectively. Silages from H1, H2 and H3 were offered for 5, 5 and 3 wk, respectively, with cows supplemented with 8.0 kg concentrate/d throughout the experiment. Digestibility of DM and the effectively degradable protein content were lower, while protein degradability was higher, for RCGS than for GS. Silage DM intakes (DMIs) were higher for RCGS than for GS at H1 and H2, with no differences at H3. Milk yield was higher with RCGS than with GS at H3, with no differences at H1 and H2. Milk fat and milk protein contents were lower with RCGS than with GS at H3 but did not differ at H1 and H2. Faecal N/N intake was higher in the RCGS group than in the GS group at H1, with no differences at H2 and H3. Gross energy digestibility was lower for RCGS than for GS at H2. Although cow performance was higher with RCGS treatment, the responses were variable between harvests, largely reflecting the changing proportion of RC in the swards as the season progresse

The effect of dietary fat and metabolizable energy supply on milk protein concentration of dairy cows

AbstractTo investigate the effect of dietary fat and metabolizable energy (ME) on milk protein concentration, an experiment was carried out using 12 multiparous early-lactation Holstein-Friesian dairy cows. Three diets were offered in a complete Latin-square change-over design, based on ad libitum access to grass silage. One of three concentrates was offered at a rate of 12 kg/day, each formulated to supply one of two levels of ME (12·1 and 13·6 MJ/kg dry matter (DM)) and one of two levels of fat (31 and a mean of 88 g acid hydrolysis ether extract per kg DM): low energy, high fat (LEHF); low energy, low fat (LELF); and high energy, high fat (HEHF). The concentration of milk protein was significantly higher from animals offered the LELF concentrate (32·5 v. a mean of 31·2 (s.e.d. 0·45) g/kg, P &lt; 0·05), because of lower milk yields (31·0 v. a mean of 33·4 (s.e.d. 0·63) kg/day, P &lt; 0·05). Animals offered the HEHF concentrate produced the highest yields of milk protein but their milk had the lowest concentrations of fat (32·5,34·4 and 31·9 g/kg for LEHF, LELF and HEHF respectively; s.e.d 1·07; P &lt; 0·05 for difference between LELF and HEHF). Silage DM intake was significantly increased by animals offered the LEHF concentrate (9·1, 8·6 and 8·7 (s.e.d. 0·19) kg/day, P &lt; 0·05 for differences between LEHF and the other two concentrates). Urinary purine derivative excretion, used as an index ofmicrobial protein supply, was highest from animals offered the LELF and HEHF concentrates, which both supplied similar amounts of fermentable ME. It is hypothesized that increased de novo synthesis offatty acids on the low fat diet reduced the availability of glucose for lactose synthesis, leading to reduced milk yields and hence increased milk protein concentrations.</jats:p

Use of grass and red clover silage mixtures for milk production and whole-body N partitioning by dairy cows

Twenty-four multiparous Holstein-Friesian dairy cows in mid lactation were used in a 44 Latin square changeover experiment with four 4-week periods to investigate the effect of altering the ratios of red clover (RC) and ryegrass silage (GS) in the forage component of their diet. Ratios (in the dry matter (DM)) were: R0, 0 RC:1 GS; R34, 0.34 RC:0.66 GS; R66, 0.66 RC:0.34 GS; R100, RC 1:0 GS. All cows received ad libitum access to their allocated forage with 4 kg of a standard concentrate per day. Results are presented in order of R0, R34, R66 and R100 respectively. Feed DM intakes (16.7, 17.8, 18.3, 19.0 kg d-1, s.e.d. 0.24, Plin<0.001) and milk yields (25.2, 26.1, 26.5, 26.1 kg d-1, s.e.d. 0.47, Plin<0.05, Pquad<0.05) increased as the proportion of RC in the forage increased. Nitrogen (N) intake and excretion of N in urine and faeces increased (P<0.01) with increasing proportion of RC in the diet, but milk N secretion as a proportion of diet N intake, decreased (P<0.01). It is concluded that the best balance of feed intakes, milk yields and efficiency of utilisation of dietary N was achieved when cows were offered a diet with RC silage as 0.66 of the forage