Genetic analysis of sow longevity and sow lifetime reproductive traits using censored data.

Sow longevity is a key component for efficient and profitable pig farming; however, approximately 50% of sows are removed annually from a breeding herd. There is no consensus in the scientific literature regarding a definition for sow longevity; however, it has been suggested that it can be measured using several methods such as stayability and economic indicators such as lifetime piglets produced. Sow longevity can be improved by genetic selection; however, it is rarely included in genetic evaluations. One reason is elongated time intervals required to collect complete lifetime data. The effect of genetic parameter estimation software in handling incomplete data (censoring) and possible early indicator traits were evaluated analysing a 30% censored data set (12 725 pedigreed Landrace × Large White sows that included approximately 30% censored data) with DMU6, THRGIBBS1F90 and GIBBS2CEN. Heritability estimates were low for all the traits evaluated. The results show that the binary stayability traits benefited from being analysed with a threshold model compared to analysing with a linear model. Sires were ranked very similarly regardless if the program handled censoring when all available data were included. Accumulated born alive and stayability were good indicators for lifetime born alive traits. Number of piglets born alive within each parity could be used as an early indicator trait for sow longevity.

Genetic associations for gilt growth, compositional, and structural soundness traits with sow longevity and lifetime reproductive performance.

The objective of this study was to estimate genetic associations for gilt growth, compositional, and structural soundness with sow longevity and lifetime reproduction. Performance and pedigree information from 1,447 commercial females from 2 genetic lines were included in the data analyzed. Growth was expressed as days to 113.5 kg BW (DAYS) and compositional traits included loin muscle area (LMA), 10th rib backfat (BF10), and last rib backfat (LRF). Structural soundness traits included body structure traits [length (BL), depth (BD), width (BWD), rib shape (BRS), top line (BTL), and hip structure (BHS)], leg structure traits [front legs: legs turned (FLT), buck knees (FBK), pastern posture (FPP), foot size (FFS), and uneven toes (FUT); rear legs: legs turned (RLT), leg posture (RLP), pastern posture (RPP), foot size (RFS), and uneven toes (RUT)], and overall leg action (OLA). Lifetime (LT) and removal parity (RP) were considered as longevity traits whereas lifetime reproductive traits included lifetime total number born (LNB), lifetime number born alive (LBA), number born alive per lifetime day (LBA/LT), and percentage productive days from total herd days (PD%). Genetic parameters were estimated with linear animal models using the average information REML algorithm. Second, to account for censored longevity and lifetime reproduction records, genetic parameters were estimated using Markov Chain Monte Carlo and Gibbs sampling methods. Similar estimates were obtained across the analysis methods. Heritability estimates for growth and compositional traits ranged from 0.50 to 0.70 and for structural soundness traits from 0.07 to 0.31. Longevity and lifetime reproductive trait heritability estimates ranged from 0.14 to 0.17 when REML was used. Unfavorable genetic correlations were obtained for DAYS with LT, RP, LNB, LBA, and PD% and for LRF with PD%. However, LMA was favorably associated with LT, RP, and LNB. Moderate to high correlations were obtained for BL and BRS with all longevity and lifetime reproductive traits. Correlations of BWD with LT and RP were moderate. Associations for leg soundness traits with longevity and lifetime reproductive traits were mainly low and nonsignificant (P ≥ 0.10). However, RLP was moderately correlated with LBA/LT and PD%. Current results indicate that selection for fewer DAYS has an antagonistic effect on lifetime performance. Furthermore, great BL, flat BRS, narrow BWD, and upright RLP seem detrimental to sow longevity and lifetime reproduction.

Genetic parameters for growth, body composition, and structural soundness traits in commercial gilts.

The objective of this study was to estimate genetic parameters for growth, body composition, and structural soundness traits in commercial gilt lines. The data included 1,449 gilts: 462 females from a grandparent maternal line and 987 from a parent maternal line. Growth was expressed as number of days to a constant 113.5 kg BW (DAYS) and compositional traits included loin muscle area (LMA), 10th rib backfat (BF10), and last rib backfat (LRF). Subjective structural soundness evaluation was completed using a 9-point scale and included: body length (BL), body depth (BD), body width (BWD), rib shape (BRS), top line (BTL), and hip structure (BHS); front legs: legs turned (FLT), buck knees (FBK), pastern posture (FPP), foot size (FFS), and uneven toes (FUT); rear legs: legs turned (RLT), leg posture (RLP), pastern posture (RPP), foot size (RFS), and uneven toes (RUT); and overall leg action (OLA). Genetic parameters were estimated with multivariate linear animal models, using the average information REML algorithm. Heritability estimates for growth and body composition traits ranged from 0.50 to 0.70, for body structure traits from 0.15 to 0.31, for leg structure traits from 0.07 to 0.31, and the estimate for OLA was 0.12. Several moderate to high genetic correlations were obtained among body structure traits, whereas correlations among leg structure traits were mainly low and nonsignificant. A strong correlation was found between FPP and OLA (P < 0.001); more upright FPP coincided with inferior OLA. Furthermore, FBK and FFS appeared to be favorably associated with OLA (0.05 < P < 0.10). Body structure trait correlations among each other and with leg soundness traits were primarily favorable. Correlations indicated that great BL and high BTL coincided with each other and deterioration of other structural soundness traits. Although genetic correlations obtained for DAYS and backfat measurements with structural soundness traits had an unfavorable trend, they were mainly low to moderate (i.e., simultaneous genetic improvement would be possible, including adversely associated traits). Due to greater heritabilities, faster genetic change could be expected for compositional and body structure traits than leg structure traits. Because of the genetic relationship among the trait groups, using information across traits when making selection decisions could result in genetic improvement among leg soundness traits.

Whole-genome association analyses for lifetime reproductive traits in the pig.

Profits for commercial pork producers vary in part because of sow productivity or sow productive life (SPL) and replacement costs. During the last decade, culling rates of sows have increased to more than 50% in the United States. Both SPL and culling rates are influenced by genetic and nongenetic factors. A whole-genome association study was conducted for pig lifetime reproductive traits, including lifetime total number born (LTNB), lifetime number born alive (LNBA), removal parity, and the ratio between lifetime nonproductive days and herd life. The proportion of phenotypic variance explained by markers was 0.15 for LTNB and LNBA, 0.12 for removal parity, and 0.06 for the ratio between lifetime nonproductive days and herd life. Several informative QTL regions (e.g., 14 QTL regions for LTNB) and genes within the regions (e.g., SLC22A18 on SSC2 for LTNB) were associated with lifetime reproductive traits in this study. Genes associated with LTNB and LNBA were similar, reflecting the high genetic correlation (0.99 ± 0.003) between these traits. Functional annotation revealed that many genes at the associated regions are expressed in reproductive tissues. For instance, the SLC22A18 gene on SSC2 associated with LTNB has been shown to be expressed in the placenta of mice. Many of the QTL regions showing associations coincided with previously identified QTL for fat deposition. This reinforces the role of fat regulation for lifetime reproductive traits. Overall, this whole-genome association study provides a list of genomic locations and markers associated with pig lifetime reproductive traits that could be considered for SPL in future studies.

Identification of genetic markers associated with fatness and leg weakness traits in the pig.

Pigs have undergone long-term selection in commercial conditions for improved rate and efficiency of lean gain. Interestingly, it has been observed in both experimental and field conditions that leg weakness has increased over time, concurrent with the selection for improved rate of lean gain, while fatter animals tend to have better leg action, and foot and leg (FL) structure. The exact molecular mechanisms or individual genes responsible for this apparent genetic correlation between fatness and leg weakness and other physical adaptability traits have been less well reported. Based on our recent studies involving candidate genes and leg weakness traits, the present investigation has identified 30 SNPs from 26 genes that were found to be associated with 10th rib backfat in a sow population consisting of 2066 animals. The specific alleles associated with increased backfat tended to be associated with better overall leg action, as shown for the genes including MTHFR, WNT2, APOE, BMP8, GNRHR and OXTR, while inconsistent associations with the single FL structure trait and backfat were observed for other genes. This study suggests that in some cases there may be a common genetic mechanism or linked genes regulating fatness and leg weakness. Such relationships are clearly complex, and the utilization of genetic markers associated with both traits should be treated cautiously.

Magnetoencephalographic (MEG) localization of the auditory N400m: effects of stimulus duration.

The effects of stimulus duration on the elicitation and equivalent current dipole (ECD) localization of the auditory N400(m) were studied in two subject groups, either familiar or unfamiliar with Finnish language, using a sentence-processing paradigm with incongruent ending words of either short or long duration. Long-duration words elicited a broad response at around 400 ms, the generator location(s) of which could not be reliably determined using ECD estimation. In contrast, short-duration words elicited a sharp, strong-amplitude response at about 400 ms latency and it's source location could be reliably determined as being in the vicinity of auditory cortex. Subjects unfamiliar with the Finnish language elicited no response at the 400 ms range. Thus, the use of short-duration words appears to be an important prerequisite for the elicitation and localization of N400m. The differential amplitude behaviour of the N400m between the two subject groups further suggests that comprehension of the semantic content of the speech message is also required.

Autoantibodies against oxidised low-density lipoprotein in patients with obstructive sleep apnoea.

Autoantibodies against oxidised low-density lipoprotein (OxLDL-Abs) have been proposed to be an indicator of endothelial dysfunction and a novel tool for finding individuals with a high cardiovascular risk. In a cross-sectional study, OxLDL-Abs were measured in 297 patients with obstructive sleep apnoea (OSA) and 54 controls using an enzyme-linked immunosorbent assay. The autoantibodies were increased in patients with OSA when compared to controls (age, body mass index (BMI) and gender adjusted, p = 0.001). However, within the OSA patients, OxLDL-Abs were not related to smoking, hypertension or BMI, and there was a weak negative correlation (r = -0.16, P = 0.007) between age and levels of OxLDL-Abs. In conclusion, at present the measurement OxLDL-Abs still remains a method for basic research and is not applicable for screening of at-risk patients with OSA.

Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease.

Oxidation of low density lipoproteins (LDL) obviously plays an important role in the pathogenesis of atherosclerosis. The purpose of the study was to determine whether antibodies against oxidized LDL are associated with coronary artery disease (CAD). We determined the serum levels of antibodies against copper-oxidized LDL by enzyme-linked immunosorbent assay in 58 patients with angiographically verified CAD and 34 controls without CAD. The mean antibody level, expressed in optical density units, was significantly higher in patients than in controls (0.150+/-0.088 versus 0.094+/-0.054, respectively; P=0.00089). In logistic regression analysis, high antibody level against oxidized LDL was associated significantly with CAD (P=0.0114), independent of age (P=0.00137), gender (P=0.0021), body mass index (P=0.5947), triglyceride concentration (P=0.9813), and total cholesterol-high density lipoprotein (HDL) cholesterol (P=0.0080) group. Similar analysis in nondiabetic subjects (n=79) and in men only (n=75) showed analogous results, with only minor changes in P values. The antibody level against oxidized LDL differed significantly between nonsmokers and smokers in CAD patients (P<0.00197) but not in controls (P=NS). In addition, the antibody level against oxidized LDL differed significantly between nonsmokers and smokers in subjects with low HDL cholesterol (0.9 mmol/L). In conclusion, elevated levels of antibodies against oxidized LDL were associated with CAD. The data suggest that oxidized LDL plays a role in the pathogenesis of atherosclerosis and suggest a protective function for HDL against LDL oxidation.

Women have a larger and less atherogenic low density lipoprotein particle size than men.

Some epidemiological studies have shown that serum total cholesterol increases with age. especially in women. On the other hand, the risk of coronary artery disease is smaller in women than in men. Earlier studies have shown that a small dense low density lipoprotein (LDL) is more atherogenic than a large LDL. We studied LDL size and apolipoprotein E (apo E) phenotypes in premenopausal and postmenopausal women and in men at the same age. In this study 342 subjects participating in a health screening study were examined. There were four subgroups: 40-year-old men (n = 85), 40-year-old women (n = 80), 70-year old men (n = 88) and 70-year-old women (n = 89). In the present study LDL size was larger (P < 0.01) in women (26.39 +/- 0.07 nm) than in men (25.95 +/- 0.07 nm). We found that LDL size correlated highly positively (r = 0.606; P < 0.001) with serum high density lipoprotein (HDL) concentration and inversely with serum triglyceride concentration (r = -0.627; P < 0.001). Measuring serum HDL cholesterol and triglycerides in health screening studies gives information indirectly about LDL size and its atherogenicity. Apo E phenotype was not significantly associated with serum triglycerides, but was associated with LDL size, LDL cholesterol, total cholesterol and HDL cholesterol. In our sample LDL size decreased and LDL cholesterol and total cholesterol increased according to the most prevalent apo E phenotypes in the order E2/3, E3/3, E3/4 and E4/4. Subjects with phenotype apo E4/4 had the smallest LDL size (25.70 +/- 0.19 nm), the highest total cholesterol (6.53 +/- 0.35 mmol/l) and the lowest HDL cholesterol values (1.28 +/- 0.04 mmol/l). We conclude that there was a significant interaction between sex and age in serum total cholesterol which was highest in older women. However, their LDL size was larger and their LDL is less atherogenic. Apo E phenotype had a significant influence on LDL size.

Apolipoprotein E polymorphism, serum lipids, myocardial infarction and severity of angiographically verified coronary artery disease in men and women.

In several populations, the apolipoprotein E (apo E) allele epsilon 4 is associated with high concentration of plasma total and low density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD). We determined the apo E phenotypes of 309 patients with angiographically verified CAD and 38 patients without CAD by isoelectric focusing and Western blotting. In men with CAD, the plasma total and LDL-cholesterol increased according to apo E phenotype in the following order: E3/2 < E3/3 < E4/3 < E4/4 (P = 0.03 for total cholesterol, P = 0.007 for LDL-cholesterol). In women, there was a similar trend (P = 0.22 for total cholesterol, P = 0.15 for LDL-cholesterol). The relative frequency of men with three vessel CAD increased (P = 0.43) together with LDL-cholesterol levels (P = 0.05) according to apo E phenotype E3/2, E3/3, E4/3, E4/4. Total and LDL-cholesterol levels were higher in patients with three vessel CAD than in patients with less serious types of CAD (P = 0.02 for total cholesterol, P = 0.007 for LDL-cholesterol). The relative frequency of patients with myocardial infarction increased according to apo E phenotype (P = 0.51). Both in men and women, there were no differences between apo E phenotypes in age at occurrence of the first myocardial infarction. The apo E allele frequencies of patients with CAD vs. without CAD were 2.3% vs. 1.3% for epsilon 2, 79.0% vs. 76.3% for epsilon 3 and 18.7% vs. 22.4% for epsilon 4. There were no statistically significant differences in apo E allele or phenotype frequencies between patients with CAD and without CAD or between patients with CAD and the general Finnish population. Our results support previous studies in suggesting that the apo E allele epsilon 4 is a risk factor for atherosclerosis, which affects plasma total and LDL-cholesterol. In addition, our results suggest that the apo E allele determines the severity of CAD.

Postprandial plasma lipoprotein changes in relation to apolipoprotein E phenotypes and low density lipoprotein size in men with and without coronary artery disease.

Postprandial lipoprotein metabolism may play a role in the etiology of premature coronary artery disease (CAD). To determine whether apolipoprotein E (apo E) polymorphism and the size of low density lipoprotein (LDL) influence postprandial lipemia we studied 39 healthy men and 35 men with CAD. Venous blood samples were obtained before an oral fat load and 3, 5 and 7 h thereafter. Total cholesterol and high density lipoprotein (HDL) cholesterol concentrations did not change in either group during the fat load, but triglycerides increased more markedly in CAD patients compared with controls independently of apo E phenotypes. There was a positive correlation between the size of LDL and the concentration of HDL cholesterol (r = 0.541, P < 0.001); conversely, an inverse correlation was observed between LDL size and the level of fasting triglycerides (r = -0.582; P < 0.001). The patients with CAD had significantly smaller LDL particles (25.89 +/- 0.56 nm) than in controls (26.21 +/- 0.63 nm) (P < 0.05). The increase in triglyceride levels during the fat load was highest in CAD patients with a small size of LDL particles (< 25.5 nm) and lowest in controls with large LDL (> 25.5 nm). Our results suggest that the magnitude of the triglyceride response is a better indicator of CAD risk than the fasting triglyceride concentration. The best model in our logistic regression analysis selected as significant risk factors the change of triglyceride concentration from the baseline at 5 h after a fat meal and HDL cholesterol. This model classified 83% of the subjects correctly.

Moderate and heavy alcohol consumption have no favorable effect on lipid values.

Moderate alcohol consumption has been reported to provide protection against coronary heart disease. We studied serum lipid values in 380 men, including 184 controls (37 teetotalers and 147 moderate drinkers), 90 heavy drinkers, and 106 alcoholics. Total cholesterol values were significantly lower among alcoholics than controls (mean +/- SEM, 5.43 +/- 0.15 mmol/L [210 +/- 5.8 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]), but their high-density lipoprotein (HDL) cholesterol values were higher (1.66 +/- 0.07 mmol/L [64 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). Accordingly, there was a highly significant difference in the HDL/total cholesterol ratio (0.32 +/- 0.13 vs 0.19 +/- 0.01). Heavy drinkers had significantly higher total cholesterol values than controls (6.30 +/- 0.13 mmol/L [244 +/- 5.0 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]); the same was true of HDL cholesterol values (1.25 +/- 0.07 mmol/L [48 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). No significant difference was found in the HDL/total cholesterol ratio between controls and heavy drinkers or between teetotalers and moderate drinkers. Therefore, moderate alcohol intake apparently does not change HDL/total cholesterol ratio; if moderate drinking is protective against coronary heart disease, the mechanism is probably not via lipids.

Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity.

Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eighty-five-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age.

Once daily compared with twice daily administration of slow-release diltiazem as monotherapy for hypertension.

We compared the efficacy of the antihypertensive drug diltiazem in a slow release formulation administered once daily with its twice daily administration as monotherapy in 34 patients with mild to moderate essential hypertension. All subjects received placebo for three weeks before the randomised, double blind, crossover study, and their supine diastolic blood pressure (BP) ranged from 95 mmHg to 115 mmHg. After the patients had received the placebo for three weeks diltiazem was titrated in the open label treatment to either 120 mg or 180 mg twice daily until the target BP level was achieved. After the open three weeks' of treatment with diltiazem twice daily patients were allocated randomly for either once daily or twice daily administration. After a six week, double blind period, the treatment was changed according to the crossover design. With a dose of 120 mg or 180 mg twice daily patients' supine and standing BP readings were significantly lower than when they took the drug once daily. In the subgroup (n = 19) with the maximum dose of diltiazem given twice daily and once daily BP levels were lower in those subjects on twice daily treatment than in those treated once a day with the same total daily dose, the differences being significant. Administration of diltiazem once a day in a slow release formulation was not as effective as a twice daily dose when the dose titration was greatest or when compared with the same dosage (240 mg x 1/day or 120 mg x 2/day).