Differential patterns in runs of homozygosity in two mice lines under divergent selection for environmental variability for birth weight.

Runs of homozygosity (ROH) are defined as long continuous homozygous stretches in the genome which are assumed to originate from a common ancestor. It has been demonstrated that divergent selection for variability in mice is possible and that low variability in birth weight is associated with robustness. To analyse ROH patterns and ROH-based genomic inbreeding, two mouse lines that were divergently selected for birth weight variability for 26 generations were used, with: 752 individuals for the high variability line (H-Line), 766 individuals for the low variability line (L-Line) and 74 individuals as a reference population. Individuals were genotyped using the high density Affymetrix Mouse Diversity Genotyping Array. ROH were identified using both the sliding windows (SW) and the consecutive runs (CR) methods. Inbreeding coefficients were calculated based on pedigree (FPED ) information, on ROH identified using the SW method (FROHSW ) and on ROH identified using the CR method (FROHCR ). Differences in genomic inbreeding were not consistent across generations and these parameters did not show clear differences between lines. Correlations between FPED and FROH were high, particularly for FROHSW . Moreover, correlations between FROHSW and FPED were even higher when ROH were identified with no restrictions in the number of heterozygotes per ROH. The comparison of FROH estimates between either of the selected lines were based on significant differences at the chromosome level, mainly in chromosomes 3, 4, 6, 8, 11, 15 and 19. ROH-based inbreeding estimates that were computed using longer homozygous segments had a higher relationship with FPED . Differences in robustness between lines were not attributable to a higher homozygosis in the L-Line, but maybe to the different distribution of ROH at the chromosome level between lines. The analysis identified a set of genomic regions for future research to establish the genomic basis of robustness.

Embryo survival and fertility differ in lines divergently selected for birth weight homogeneity in mice.

The selection of animals for lower environment sensitivity around the optimum trait value can also provide benefits in productivity and welfare. A divergent selection experiment for birth weight environmental variability in mice was successfully conducted over 17 generations. Animals from low variability selected line (L-line) were more robust by having a higher litter size and survival at weaning in a common breeding environment, than those from high variability line (H-line). The objective of this study was to analyze the differences between those divergently selected lines for embryo and fetal survival and for fertility and prolificacy rate. To study embryo survival and ovulation rate, a total of 98 females (34 H-line and 50 L-line) were studied in four generations of the divergent experiment. To analyze fetal survival and fertility rate, 378 female mice (138 H-line and 240 L-line) in 10 generations or the divergent experiment were studied. Ultrasound scans were performed at day 14 of gestation to establish the number of total fetal and the embryo absorptions. Mortality was addressed as the difference between litter size at birth and the number of fetuses at 14 days of gestation. The number of pregnant females in the first 3 days after mating was used to measure fertility. A linear model was also fitted to analyze embryo mortality, litter size, and the number of embryos at 14 days of gestation. A categorical model was then used to study fertility, including line, generation, and its interaction as effects. Despite the fact that there were no significant differences in the ovulation rate, litter size at birth was significantly higher in the L-line than in the H-line (9.82 vs. 8.36 pups, p < 0.001). Moreover, embryo mortality was significantly lower in the L-line than in the H-line (1.39 vs. 2.87 fetuses, p < 0.001). L-line females were more fertile (53.49% vs. 23.26% for the H-line). According to these results, the line selected for low environmental variance would be preferable for robustness and animal welfare.

Impact of selection for birth weight variability on reproductive longevity: A mice model.

Uniformity, understood as a similar performance in relevant livestock traits, such as birth weight within the litter, is being included as one of the selection objectives in breeding programmes, especially for polytocous livestock species. A divergent selection experiment for birth weight within-litter variability in mice during 23 generations showed that homogeneous animals were better for litter size, survival and feed efficiency but less heavy than heterogeneous animals. The aim of this study was to compare the reproductive longevity in both divergent lines as time to the end of the reproductive period. Two generations from both lines with an initial number of 43 females and 43 males were mated one to one and stayed together to have consecutive parturitions until the end of the reproductive life. Females were discarded when the time elapsed from the last parturition was longer than 63 days. The time to the end of the reproductive period between both lines was compared by fitting a Cox proportional hazard regression model adjusting for line, generation and its interaction. The rate of parturitions in both lines was also compared using a Prentice-Williams-Peterson model adjusted for the same effects. The low variability line was associated with a higher parturition rate, e.g., adjusted hazard ratio was 2.93 (95% CI 2.17-3.94). The Cox model showed that the low variability females also presented benefits of time to the end of the reproductive period, with an adjusted hazard ratio of 0.26 (95% CI 0.16-0.41). The median of reproductive days was 55.50 in the high variability line whilst the median was 252.50 days for the low variability females. The homogeneous line presented important reproductive advantages suggesting higher robustness and animal welfare. Further research should confirm whether the findings presented here of a better performance in the low variability line could be properly applied to some livestock species.

Calving date and its variability as a potential trait in the breeding objective to account for reproductive seasonality in alpacas.

The low fertility and offspring survival indicators in alpacas can be partially due to their particularity seasonal reproduction that reduces the opportunities of the females to become pregnant within a season, with the survival of the offspring concerned by the availability of food and exposure to diseases that depends on the calving date. Optimizing the date of delivery and reducing its variability are shown as eligible criteria that could be used as selection criteria within the genetic improvement programmes in alpacas, the calving date being a much more appropriate trait to measure and optimize fertility unlike of age at first calving and the calving interval, this due to the reproductive seasonality in camelids. For this study, 6,533 birth date records were taken between 2001 and 2018 of Peruvian alpacas, to estimate the genetic parameters. Models assuming heterogeneity in the residuals were fitted besides classical homogeneous models to address, not only the possibility of forwarding or delaying the calving date, but also the trend to have parturitions in similar dates. The heritability and repeatability ranged from 0.07 to 0.20 for a homogeneity model and from 0.08 to 0.23 for a heterogeneity model, and suggest the possibility of advancing or delaying the calving date. It should be taken into account that the gestation length of camelids makes it difficult to adapt many reproductive traits, and trying to centre the calving date could delay it. It was concluded the feasibility to genetically select the calving date, also in the production of camels and dromedaries, which have the same reproductive characteristics as alpacas. This selection can be combined with other traits. The heterogeneity model was shown to provide a better fit.

Effect of feed restriction on the environmental variability of birth weight in divergently selected lines of mice.

BACKGROUND: Selection of mice for decreased environmental variability of birth weight has achieved higher survivability and larger litter size as a correlated response to canalized selection, which suggests higher welfare and robustness, and animals that are more homogeneous. However, in these studies, animals were not exposed to an environmental challenge. To demonstrate the advantages of this mouse line with a low environmental variability of birth weight, animals from two divergent lines (high and low variability of birth weight) were subjected to feed restriction. The objective of this study was to use these divergent lines to compare their response in terms of robustness against an environmental challenge. At weaning, 120 females, i.e. four full-sib females from 10 random litters of three consecutive generations of selection, were chosen from these divergent lines. The total number of females was divided into four groups, which were subjected to a feeding regimen by imposing different levels of feed restriction (i.e. 75, 90 and 85% of full ad libitum feed across three generations, respectively) in different combinations during the growth and reproduction periods. RESULTS: Animals from the "low" line were less sensitive to a change in feed level than those from the "high" line. Regarding reproduction, the "low" line performed better in terms of number of females having parturitions, number of parturitions, and litter size. Imposing a feed restriction on female mice during their growth period did not affect the birth weight of their pups. The "low" line was preferred because of its higher reproductive efficiency and survival under an environmental challenge. CONCLUSIONS: Selection for decreased environmental variability of birth weight produces animals that are less sensitive to environmental conditions, which can be interpreted as having greater robustness.

Feed and reproductive efficiency differences between divergently selected lines for birthweight environmental variability in mice.

Sustainability has come to play an important role in agricultural production. A way to combine efficiency with sustainability might be by searching for robust animals that can be selected for the homogeneity of certain traits. Furthermore, the optimization of feed efficiency is one of the challenges to improve livestock genetics programmes, but this might compromise reproductive efficiency. Animals from two divergent mouse lines, regarding variability of birthweight, were used to check whether homogeneity was also related to both feed and reproductive efficiency. The objective of this study was to use these divergent lines of mice to compare them with their feed efficiency and the reproductive capacity. Animal weight, weight gain, feed intake, relative intake and cumulated transformation index were considered as feed efficiency traits. Animals from the low line had both lower weight and feed intake from 21 to 56 days. They had a worse transforming index in the three last weeks when litter size was fitted as an effect of the model, but the lines become similar if the higher litter size of the low line was not included. Reproductively, the low line performed better considering the number of females having parturitions, the number of parturitions, and with higher litter size and survival in both parturitions. Hence, the low variability line was preferred because of reproductive efficiency without seriously affecting its feed efficiency. Homogeneity seemed to be related to robustness with similar feed efficiency but higher reproductive efficiency.

Genomic inbreeding measures applied to a population of mice divergently selected for birth weight environmental variance.

This study aimed to compare different inbreeding measures estimated from pedigree and molecular data from two divergent mouse lines selected for environmental birth weight during 26 generations. Furthermore, the performance of different approaches and both molecular and pedigree data sources for estimating Ne were tested in this population. A total of 1,699 individuals were genotyped using a high-density genotyping array. Genomic relationship matrices were used to calculate molecular inbreeding: Nejati-Javaremi (F NEJ), Li and Horvitz (F L&H), Van Raden method 1 (F VR1) and method 2 (F VR2), and Yang (F YAN). Inbreeding based on runs of homozygosity (F ROH) and pedigree inbreeding (F PED) were also computed. F ROH, F NEJ, and F L&H were also adjusted for their average values in the first generation of selection and named F ROH0, F NEJ0, and F L&H0. ∆F was calculated from pedigrees as the individual inbreeding rate between the individual and his parents (∆F PEDt) and individual increases in inbreeding (∆F PEDi). Moreover, individual ∆F was calculated from the different molecular inbreeding coefficients (∆F NEJ0, ∆F L&H, ∆F L&H0, ∆F VR1, ∆F VR2, ∆F YAN, and ∆F ROH0). The Ne was obtained from different ∆F, such as Ne PEDt, Ne PEDi, Ne NEJ0, Ne L&H, Ne L&H0, Ne VR1, Ne VR2, Ne YAN, and Ne ROH0. Comparing with F PED , F ROH , F NEJ and F VR2 overestimated inbreeding while F NEJ0 , F L&H , F L&H0 , F VR1 and F YAN underestimated inbreeding. Correlations between inbreeding coefficients and ∆F were calculated. F ROH had the highest correlation with F PED (0.89); F YAN had correlations >0.95 with all the other molecular inbreeding coefficients. Ne PEDi was more reliable than Ne PEDt and presented similar behaviour to Ne L&H0 and Ne NEJ0. Stable trends in Ne were not observed until the 10th generation. In the 10th generation Ne PEDi was 42.20, Ne L&H0 was 45.04 and Ne NEJ0 was 45.05 and in the last generation these Ne were 35.65, 35.94 and 35.93, respectively F ROH presented the highest correlation with F PED, which addresses the identity by descent probability (IBD). The evolution of Ne L&H0 and Ne NEJ0 was the most similar to that of Ne PEDi. Data from several generations was necessary to reach a stable trend for Ne, both with pedigree and molecular data. This population was useful to test different approaches to computing inbreeding coefficients and Ne using molecular and pedigree data.

Differential sensitivity of climate conditions on birth weight genetic values in mice divergently selected for birth weight residual variance.

After 32 generations of a divergent selection experiment for residual variance of birth weight in mice, two divergent lines were thus obtained: the heterogeneous line (H-line) and the homogeneous line (L-line). Throughout the generations, differences were observed between the two lines in traits such as litter size, survival at weaning, and birth weight variability caused by unidentified environmental conditions. The L-line exhibited advantages in terms of higher survival rates, larger litter sizes, and less sensitivity to changes in food intake. The study is an examination of the effects of climate as an environmental factor on the performance of these animals. Climate factors including maximum, minimum, and mean temperature (T), humidity (H), and TH index; at three stages (the fecundation, a week before the parturition and the parturition), were linked to a birth weight dataset consisting of 22,614 records distributed as follows: 8,853 corresponding to the H-line, 12,649 to the L-line, and 1,112 to the initial population. Out of the 27 analyzed climatic variables, the maximum temperature 1 wk before parturition (MXTW) was identified as the most influential when comparing heteroscedastic models with the deviance information criterion. The order of Legendre polynomial to apply in the following random regression model was tested by a cross-validation using homoscedastic models. Finally, MXTW was compared on how it affected the two divergent lines by analyzing predicted breeding values (PBV) obtained from a random regression heteroscedastic model. The mean PBV of the H-line in the first generation showed a range of 0.070 g with a negative slope, which was 35 times higher than the range obtained for the L-line, which varied within 0.002 g. In the last generation of selection, the H-line exhibited greater instability of PBV across temperatures, with a difference of 0.101 g between the maximum and minimum mean PBV, compared to 0.017 g for the L-line. The standard deviations of the slopes in the H-line were more dispersed than in the L-line. Unlike the H-line, the L-line had slopes that were not significantly different from 0 throughout the generations of selection, indicating greater stability in response to MXTW variations. The H-line exhibited a higher sensitivity to changes in MXTW, particularly in birth weight, with the L-line being more stable. The selection for uniformity of birth weight could lead to less sensitive animals under environmental changes.

Two mice lines obtained by divergent selection for birth weight residual variance were used to determine whether environmental factors could differently affect the homogeneous and heterogeneous lines. The maximum temperature 1 wk before parturition (MXTW) had the higher impact on the birth weight of the animals. A random regression model showed the individual trajectory of birth weight throughout the changes in MXTW. It was evident that the homogeneous line is less susceptible to changes in climate. This result, therefore, supports the hypothesis that the selection for homogeneity in production animals is more advantageous. More robust animals are obtained that can better cope with changes in climate without compromising their productive traits.

Genetic parameters for fleece uniformity in alpacas.

Fiber diameter is the main selection objective and criterion in alpaca breeding programs, but it can vary across anatomic regions of the animal. As fiber diameter is usually registered from a unique sample from the mid side of the body, fiber diameter variability within fleece is never addressed and phenotypic and genetic differences may exist for fleece uniformity in alpaca populations. The objective of this work was to estimate the genetic parameters of fleece uniformity in an alpaca population. Fiber diameters measured in three different locations were used as repeated records of the same animal and studied for fitting a model that considers heterogeneous the residual variance of the model. Also, the logarithm of the standard deviation of the three measures was used as a measure of the fleece variability. Estimate of the additive genetic variance of the environmental variability was 0.43±0.14, enough high to suggest the existence of wide room to select for fleece uniformity. Genetic correlation of the trait with its environmental variability was 0.76±0.13 showing that fleece uniformity will be indirectly selected when aiming to reduce the fiber diameter. In the light of these parameters, and due to the cost of registering and the cost of opportunity, it looks no worthy to include uniformity as a selection criterion in alpaca breeding programs.

The quality of alpaca fiber is mainly assessed by a low fiber diameter. However, the fiber diameter can greatly vary along the different body locations of the animal, the industry demands not only the fineness of the fiber but also the fleece uniformity. This work studied the genetic parameters related to fleece uniformity by analyzing the diameter of three samples from different body locations (mid side, shoulder, and thigh) under two different models of analysis. The results showed variability between sampling locations and the existence of important genetic variability susceptible to being used in alpaca selection. Nevertheless, selection based on a single measurement could be used as the high correlations between locations and between the trait and its variability, saving the cost of sample analyses, being the fleece uniformity indirectly selected.

Long-Distance Transport of Finisher Pigs in the Iberian Peninsula: Effects of Season on Thermal and Enthalpy Conditions, Welfare Indicators and Meat pH.

Current legislation in the European Union places limits on live pig transport according to outside temperature, but less is known about the effects of sudden changes in the thermal microenvironment in trailers, particularly during long-distance transport. In this study, we measured the temperature and relative humidity inside livestock vehicles carrying 1920 Spanish finisher pigs (live weight 100 kg and 240 animals per journey) during eight long-distance (>15 h) commercial journeys to slaughter from northern Spain to Portugal in the summer and winter. Here, we report the rate of change in the air temperature (°C × min-1) and air enthalpies in the transport vehicle (kg water kg dry air-1). At sticking, blood samples were taken for to measure cortisol, glucose, and creatine kinase (CK) as stress response indicators, and the meat pH after 45 min and the pH after 24 h were also determined. The rate of change in the air temperature and enthalpy was higher inside the livestock vehicle during the winter months and was positively related with higher cortisol and glucose levels and lower pH after 45 min (p < 0.05). It is proposed that the rate of temperature change and air enthalpy represent useful integrated indices of thermal stress for pigs during transport.

Influence of Different Regimes of Moderate Maternal Feed Restriction during Pregnancy of Primiparous Rabbit Does on Long-Term Metabolic Energy Homeostasis, Productive Performance and Welfare.

In this study, a maternal feed restriction (MFR; 105 g/d) in primiparous rabbit does was applied from day 0 to 7 post artificial insemination (AI) (R07, n = 96), from day 7 to 21 post AI (R721, n = 92), from day 0 to 21 post AI (R021, n = 94) or fed ad libitum during whole pregnancy (Control, n= 92). Feed intake (FI) was measured after MFR was over. On day 28 of gestation, fetoplacental development was evaluated (n = 11/group) and the productive parameters of the remaining dams were analyzed. Plasma free tri-iodothyronine (T3) and thyroxine, glucose, insulin, non-esterified fatty acids (NEFA), and corticosterone were analyzed during gestation and lactation (n = 5/group). After MFR, all groups significantly increased their voluntary FI. The longer MFR was, the lower the weight and length of the fetuses, but no long-term effects over litter performance were observed. R021 groups had the lowest T3 and the highest NEFA concentrations during pregnancy and showed insulin resistance at the end of gestation, but during lactation, energy homeostasis was balanced in all groups. MFR did not affect corticosterone concentrations. In conclusion, the ration setting applied slightly involved the energy homeostasis and metabolism of the animals, but their overall metabolic condition, productive performance and welfare were not compromised.

Selection Response in a Divergent Selection Experiment for Birth Weight Variability in Mice Compared with a Control Line.

Birth weight (BW) in animal production is an economically important trait in prolific species. The laboratory mouse (Mus musculus) is used as an experimental animal because it is considered a suitable model for prolific species such as rabbits and pigs. Two mouse lines were divergently selected for birth weight variability with a third line of non-selected control population of the same origin as the animals starting the experiment. The objective of this study was, therefore, to compare and evaluate the differential response of each line. The animals were from the 17th generation of both low and high BW variability lines of the divergent selection experiment, including in addition animals from the control line. The dataset contained 389 records from 48 litters of the high line, 734 records from 73 litters of the low line, and 574 records from 71 litters of the control line. The studied traits were as follows: the BW, the BW variance, the BW standard deviation, the BW coefficient of variation within-litter, the weaning weight (WW), the litter size at birth and at weaning, the weight gain, and the preweaning survival. The model included the line effect jointly with the parturition number and its interaction, the linear and quadratic LS as covariates except for the LS trait itself when analyzing litter traits, as well as the pup sex when analyzing individual traits. The low line had a lower BW and WW, but a higher litter size, and greater robustness owing to a higher survival at weaning. As a model of livestock animals, the findings from this experiment led to a proposal of selection for pig production that would combine an increase in litter size with higher survival and welfare. Compared with the control line, a much higher response was observed in the low variability line than in the high line, making it extremely satisfactory given that homogeneity provides advantages in terms of animal welfare and robustness.

The Statistical Scale Effect as a Source of Positive Genetic Correlation Between Mean and Variability: A Simulation Study.

The selection objective for animal production is the highest income with the lowest production cost, while ensuring the highest animal welfare. A selection experiment for environmental variability of birth weight in mice showed a correlated response in the mean after 20 generations starting from a crossed panmictic population. The relationship between the birth weight and its environmental variability explained the correlated response. The scale effect represents a potential cause of this correlation. The relationship between the mean and the variability implies: the higher the mean, the higher the variability. The study was to quantify by simulation the genetic correlation between a trait and its environmental variability. This can be attributable to the scale effect in a range of coefficients of variation and heritabilities between 0.05 and 0.50. The resulting genetic correlation ranged from 0.1335 to 0.7021 being the highest for the highest heritability and the lowest CV. The scale effect for a trait with heritability between 0.25 and 0.35 and CV between 0.15 and 0.25 generated a genetic correlation between 0.43 and 0.57. The genetic coefficient of variation (GCV) affecting residual variability was modulated by the strength reducing the impact of the scale effect. GCV ranged from 0.0050 to 1.4984. The strength of the scale effect might be in the range between 0 and 1. The scale effect would explain many reported genetic correlation and the additive genetic variance for the variability. This is relevant when increasing the mean of a trait jointly with the reduction of its variability.

Supplementation with Fish Oil Improves Meat Fatty Acid Profile although Impairs Growth Performance of Early Weaned Rabbits.

Our objective was to analyze the influence of replacing lard (control) with fish oil (FO) rich in long-chain n-3 polyunsaturated fatty acids in the diet of rabbits weaned at 25 days of age on their growth performance, meat quality, cecal fermentation, and ileal morphology. Twenty-four litters (12 control and 12 FO) of nine kits each were fed the experimental diets from weaning (25 days) until slaughter at 60 days of age. Half of the litters (six per diet) were used to monitor productive performance, carcass characteristics, and ileal morphology, and cecal fermentation was assessed in the rest of litters. Diet had no influence on feed intake, meat color, and pH or cecal fermentation, but FO-fed rabbits had lower (p ≤ 0.049) average daily gain, chilled carcass weight, and perirenal fat than control rabbits. Fish oil inclusion in the diet resulted in lower morbidity (5.56% vs. 20.4%; p = 0.019) and a healthier fatty acid profile with lower (p < 0.001) n-6/n-3 ratios in both muscle and perirenal fat. In summary, the inclusion of FO in the diet of early weaned rabbits improved the fatty acid profile of rabbit meat and fat and decreased the morbidity, but growth performance was slightly reduced.