Long-term selection for litter size in swine results in shifts in allelic frequency in regions involved in reproductive processes.

High-density genotype data were analyzed in three lines of swine that express substantial variation in sow fertility to uncover regions of the genome potentially influenced during selection for litter size traits. The experimental lines examined include the Nebraska Index Line (NIL), which has been subjected to long-term selection for litter size; a control line derived from the same population that founded NIL; and a commercial Duroc × Hampshire (D × H) population, in which no selection for litter size was practiced. Regions of the genome potentially affected by selection for litter size traits in NIL were determined by multiple lines of evidence, including altered allelic frequency compared to the other lines, loss of heterozygosity and relative extended haplotype homozygosity. Additionally, a genome-wide association study for litter size traits was conducted in a population based on NIL and commercial maternal line genetics. Several genomic regions identified as putative signatures of selection overlapped with QTL for litter size traits. One of these regions, located on SSC2 (13-14 Mb), includes the candidate gene P2X3R, which plays a role in implantation and sustained release of hormones associated with reproductive processes. Sequencing identified synonymous SNPs in P2X3R that are fixed in NIL but polymorphic with nearly equal frequencies in the D × H line, indicating a potential role of P2X3R in sow fertility. These results suggest that data derived from these lines can help to uncover and understand a portion of the genetic variance associated with fertility traits in swine.

Analysis of 28 generations of selection for reproduction, growth, and carcass traits in swine.

Selection (28 generations, G) in a Large White-Landrace composite population for traits aimed at increasing live pigs born per litter (BA), with additional selection for increased 180-d weight (WT180) and longissimus muscle area (LMA) and decreased back fat (BF10) in the last 8 generations, was practiced. Objectives herein were to estimate genetic and phenotypic responses and genetic parameters (n = 1,883 to 54,174) and to investigate whether a plateau in response for BA occurred. Line 2 (L2) was selected for an index of ovulation rate and embryo survival (G0 to G11), fully formed pigs (FF) per litter (G12 to 14), and BA and pig birth weight (PBW, G15 to G19), and its control line (LC1) was selected randomly (G0 to G21). Line 4 (L4), derived from L2, and line 5 (L5), derived from LC1, at G8 were selected in 2 stages for ovulation rate and FF (G9 to G16) and BA and PBW (G17 to G19), and their control (LC6) was selected randomly. At G20, L4 and L5 were crossed to form L45, and L4 and L2 were crossed to continue L2; L2 and L45 were subsequently selected for BA, WT180, LMA, and BF10 (G21 to G28). At G21, LC1 and LC6 were reciprocally crossed to form LC16, control for L2, and LC61, control for L45. Selection in L2 and L45 was first for BA and then for other traits among pigs selected for BA. Line sizes were 40 to 60 litters by 15 to 20 sires/G. Cumulative selection differentials (CSD) were calculated. MTDFREML was used to estimate variance components, EBV, and responses. Genetic changes at G28 in L2 were 4.63 FF and 3.66 BA, with 72% (FF) and 86% (BA) of the change occurring after G11. Two-stage selection produced similar responses (P < 0.01) in FF in L4 and L5 (0.27 and 0.29 pigs/G) but a greater response in BA in L5 (0.19 vs. 0.28 pigs/G). Genetic change in L45 from G20 to G28 was 0.17 pigs/G for both FF and BA (P < 0.01). Genetic changes at G28 in L45 were 4.16 FF and 3.68 BA. Genetic correlations of reproductive and growth traits were near zero, ranging from -0.43 (stillborn pigs/litter with BF10) to 0.21 (mummies/litter with LMA). Selection for growth traits along with litter size selection during G19 to G28 resulted in responses consistent with the selection applied and the heritability of the trait. No evidence for a selection plateau existed; selection differentials and variances of FF and BA in selection lines during G20 to G28 were similar to those in earlier generations. Over all generations, heritability of BA was 0.20 ± 0.03 and remained at approximately 0.17 in selection lines in later generations.

Genomic analysis of the differential response to experimental infection with porcine circovirus 2b.

Porcine circovirus type 2 (PCV2) is the etiological agent of a group of associated diseases (PCVAD) that affect production efficiency and can lead to mortality. Using different crossbred lines of pigs, we analyzed host genetic variation of viral load, immune response and weight change following experimental infection with a PCV2b strain (n = 386). Pigs expressed variation in the magnitude and initiation of viremia and immune response recorded weekly until 28 days post-infection. A higher viral load was correlated with weight gain (r = -0.26, P < 0.0001) and presence of PCV2-specific antibodies (IgM, r = 0.26-0.34, P < 0.0001; IgG, r = 0.17-0.20, P < 0.01). In genome-wide association analyses of the responses at different time points, the proportions of phenotypic variation explained by combined effects of 56 433 SNPs were 34.8-59.4% for viremia, 10.1-59.5% for antibody response and 5.6-14.9% for weight change. Relationships between genomic prediction of overall viral load and weight gain during the first weeks of challenge were negative (-0.21 and -0.24 respectively, P < 0.0001). Individuals that carried more favorable alleles across three SNPs on SSC9 (0.60 Mb) and SSC12 (6.8 and 18.2 Mb) partially explained this relationship, having lower viral load (P < 0.0001); lower viremia at day 14 (P < 0.0001), day 21 (P < 0.01) and day 28 (P < 0.05) and greater overall average daily gain during infection (ADGi ; P < 0.01), ADGi at week 3 (P < 0.001) and week 4 (P < 0.01). These additive genetic relationships could lead to molecular solutions to improve animal health and reduce production costs.

Acute tubular injury is an important component in type I acute antibody-mediated rejection.

BACKGROUND: "Acute tubular necrosis (ATN)-like" changes in type I acute antibody- mediated rejection (AAMR) have been proposed since 2005, but the presence of "ATN-like" injury in AAMR has not well been established. The aim of this study was to confirm the presence of acute tubular injury in type I AAMR, using the specific proximal tubular injury marker, kidney injury molecule-1 (KIM-1). DESIGN: The study included 3 groups of cases, namely, a negative control group (normal nontransplantation renal parenchyma as group 1, n = 11), a positive control group (transplant ATN with negative C4d staining as group 2, n = 12), and study cases (type 1 AAMR as group 3, n = 19). Biopsy specimens from all groups were stained immunohistochemically for KIM-1 (monoclonal antibody) and KIM-1 staining intensity in proximal tubules was graded from 0.5 to 3+. Clinical indices were also correlated and analyzed. RESULTS: Group 1 demonstrated significantly lower serum creatinine levels (1.02 ± 0.10 mg/dL) when compared with both group 2 and group 3. Both groups 2 and 3 showed similar serum creatinine levels (4.02 ± 0.59 mg/dL in group 2 and 3.24 ± 0.34 mg/dL in group 3). The negative control group demonstrated negative proximal tubule staining for KIM-1, whereas both groups 2 and 3 showed positive KIM-1 staining in proximal tubules (intensity ranging from 1+ to 3+ in group 2 and from 0.5 to 3+ in group 3). CONCLUSION: Our results, using KIM-1 immunohistochemistry, demonstrated that acute tubular injury is an important component of type I AAMR.

Genome-wide prediction of age at puberty and reproductive longevity in sows.

Traditional selection for sow reproductive longevity is ineffective due to low heritability and late expression of the trait. Incorporation of DNA markers into selection programs is potentially a more practical approach for improving sow lifetime productivity. Using a resource population of crossbred gilts, we explored pleiotropic sources of variation that influence age at puberty and reproductive longevity. Of the traits recorded before breeding, only age at puberty significantly affected the probability that females would produce a first parity litter. The genetic variance explained by 1-Mb windows of the sow genome, compared across traits, uncovered regions that influence both age at puberty and lifetime number of parities. Allelic variants of SNPs located on SSC5 (27-28 Mb), SSC8 (36-37 Mb) and SSC12 (1.2-2 Mb) exhibited additive effects and were associated with both early expression of puberty and a greater than average number of lifetime parities. Combined analysis of these SNPs showed that an increase in the number of favorable alleles had positive impact on reproductive longevity, increasing number of parities by up to 1.36. The region located on SSC5 harbors non-synonymous alleles in the arginine vasopressin receptor 1A (AVPR1A) gene, a G-protein-coupled receptor associated with social and reproductive behaviors in voles and humans and a candidate for the observed effects. This region is characterized by high levels of linkage disequilibrium in different lines and could be exploited in marker-assisted selection programs across populations to increase sow reproductive longevity.

Cost minimisation analysis of using acellular dermal matrix (Strattice™) for breast reconstruction compared with standard techniques.

BACKGROUND: We performed a cost analysis (using UK 2011/12 NHS tariffs as a proxy for cost) comparing immediate breast reconstruction using the new one-stage technique of acellular dermal matrix (Strattice™) with implant versus the standard alternative techniques of tissue expander (TE)/implant as a two-stage procedure and latissimus dorsi (LD) flap reconstruction. METHODS: Clinical report data were collected for operative time, length of stay, outpatient procedures, and number of elective and emergency admissions in our first consecutive 24 patients undergoing one-stage Strattice reconstruction. Total cost to the NHS based on tariff, assuming top-up payments to cover Strattice acquisition costs, was assessed and compared to the two historical control groups matched on key variables. RESULTS: Eleven patients having unilateral Strattice reconstruction were compared to 10 having TE/implant reconstruction and 10 having LD flap and implant reconstruction. Thirteen patients having bilateral Strattice reconstruction were compared to 12 having bilateral TE/implant reconstruction. Total costs were: unilateral Strattice, £3685; unilateral TE, £4985; unilateral LD and implant, £6321; bilateral TE, £5478; and bilateral Strattice, £6771. CONCLUSIONS: The cost analysis shows a financial advantage of using acellular dermal matrix (Strattice) in unilateral breast reconstruction versus alternative procedures. The reimbursement system in England (Payment by Results) is based on disease-related groups similar to that of many countries across Europe and tariffs are based on reported hospital costs, making this analysis of relevance in other countries.

Effects of restricting energy during the gilt developmental period on growth and reproduction of lines differing in lean growth rate: responses in feed intake, growth, and age at puberty.

The overall objective was to compare reproductive performance through 4 parities of gilts developed with ad libitum access to feed or with restriction of energy to 75% of ad libitum intake. Effects on growth and pubertal development are reported. The experiment was a 2 × 2 factorial with 661 gilts. One-half of the gilts (n = 330) were allowed ad libitum access to feed from weaning to breeding at 235 d of age (AL), and 331 littermates were developed with ad libitum access to feed to 123 d of age and then restricted to 75% of ad libitum intake to 235 d of age (Res). Diets for gilts on regimen AL were formulated to meet requirements for growth. All nutrients except energy and selenium were increased in the diet fed to gilts on regimen Res so that nutrient intake per unit of BW was expected to be similar to that of gilts on regimen AL. Sires of all gilts were from an industry maternal line. Dams were either an industry Large White-Landrace cross, or Nebraska selection Line 45, producing gilts denoted as LW/LR and L45X, respectively. Traits were recorded every 2 wk. Recording of feed intake and BW began at 53 d of age, and recording of backfat (BF) and LM area (LMA) began at 123 d of age. Estrus detection began at 140 d of age to determine age at puberty (AP). The G:F ratio from 123 to 235 d of age for gilts on the AL regimen was greater (0.269 vs. 0.257, P < 0.01) than for gilts on the Res regimen; the greatest difference occurred in the first 2-wk period following feed restriction. The LW/LR gilts were heavier, had less BF, and had greater LMA than L45X gilts, but interactions with feeding regimen and period of development existed. Feed restriction reduced BW, BF, LMA, and ratio of BF to BW, but had little effect on ratio of LMA to BW. More L45X gilts than LW/LR gilts (98 vs. 93%, P < 0.01) and more gilts developed on regimen AL than regimen Res (98 vs. 91%, P < 0.01) expressed estrus. Mean age at puberty was 178.6 d for LW/LR and 173.0 d for L45X gilts (P < 0.01) and 174.1 d for regimen AL and 177.5 d for regimen Res (P < 0.05). The Res regimen delayed pubertal development. Subsequently, it will be important to determine effects on reproduction through 4 parities.

Factors associated with sow stayability in 6 genotypes.

The purpose of this study was to determine the association of production factors with stayability to parity 4 (STAY4) under controlled experimental conditions. Data were from 2,293 female pigs, sampled from 6 genetic lines that were entered into the National Pork Producers Council Maternal Line National Genetic Evaluation Program. Genetic lines evaluated included Newsham (NH), National Swine Registry (NSR), American Diamond Swine Genetics (ADSG), Danbred (DAN), and 2 Dekalb-Monsanto lines (DK44 and GPK347). Stepwise logistic regression was utilized in the analysis of STAY4. All effects were nested within genetic line. Categorical effects in the model were arrival date to the wean-to-finish unit (entry date) and breed-gestation-farrowing facility (farm). Continuous effects in the model were gilt backfat, LM depth, ADG, age at puberty, age at first farrowing, and traits recorded before the last litter of the sow (prefarrow backfat, number born alive, number weaned, litter weaning weight, lactation feed intake, lactation backfat loss, and lactation length). Factors significant for STAY4 included farm, entry date, age at first farrowing, ADG, gilt backfat, and lactation before removal effects, as well as feed intake, number born alive, and lactation length. Age at first farrowing and lactation feed intake affected all genetic lines. Regression coefficients for STAY4 on age at first farrowing were -0.014, -0.022, -0.017, -0.016, -0.011, and -0.021 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN genetic lines. Regression coefficients for STAY4 on lactation feed intake were 0.043, 0.049, 0.051, 0.061, 0.120, and 0.097 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN females. Age at puberty, age at first farrowing, and lactation feed intake had the greatest effect on STAY4.

Effect of pen mates on growth, backfat depth, and longissimus muscle area of swine.

Records on final BW (kg), backfat depth (cm), and LM area (cm(2)) of pigs from a University of Nebraska Large White/Landrace composite population were analyzed to estimate the effects of pen mates. Measurements were at approximately 180 d of age for 3,524 pigs in 351 pens (9 to 11 pigs per pen) farrowed from 1999 to 2005. The area of each pen was 8.13 m(2). The full model (M1) included the fixed effects of contemporary group, sex, line, and the covariates of age and inbreeding coefficient, and included random direct genetic, genetic pen-mate, permanent environmental, pen, litter, and residual effects. A derivative-free algorithm was used to obtain REML estimates of variance components for final BW adjusted to 180 d of age with M1 and 7 reduced models, and with 4 reduced models for the carcass traits. For final BW, likelihood ratio tests showed that M1 did not fit the data better than model 2 (permanent environmental effect omitted from M1) or model 3 (pen omitted from M1). Model 2 was not significantly (P > 0.05) better than model 3, which shows that variance attributable to pen effects and permanent environmental effects cannot be separated. Large sampling variances of estimates of the pen component of variance for models with pen-mate effects also indicate an inability to separate pen effects from the effects of pen mates. When pen-mate genetic effects were not in the model, estimates of components of variance and the fit of the data were the same for models 4 (included both permanent environmental and pen effects), 6 (included pen effects), and 7 (included permanent environmental effects), which shows that including both pen and permanent environmental effects was no better than including one or the other. Models 4, 6, and 7 were significantly better than model 8, which did not include pen-mate effects and pen effects, implying that pen effects are important. The estimate of pen variance with model 2 was approximately (number of pen mates - 1) times the estimate of variance of pen-mate permanent environmental effects with model 3. Patterns of estimates of variance components with models 2, 5, 6, and 8 for backfat depth and LM area were similar to those for final BW. Estimates of direct genetic variance and phenotypic variance were similar for all models. Estimates of heritability for direct genetic effects were approximately 0.40 for final BW, 0.45 for backfat depth, and 0.27 for LM area. Estimates of heritability for pen-mate genetic effects were 0.001 for the 3 traits for models including either pen or permanent environmental effects. Under the management conditions for this experiment, the conclusion is that the model for genetic evaluation should include litter effects and either pen effects or pen-mate permanent environmental effects and possibly genetic pen-mate effects, in general agreement with the results of studies of different populations at other locations.