Effective population size and inbreeding depression on litter size in rabbits. A case study

The purpose of this study is to use demographic and litter size data on four Spanish maternal lines of rabbits (A, V, H and LP), as a case study, in order to: (i) estimate the effective population size of the lines, as a measure of the rate of increase of inbreeding, and (ii) study whether the inbreeding effect on litter size traits depends on the pattern of its accumulation over time. The lines are being selected for litter size at weaning and are kept closed at the same selection nucleus under the same selection and management programme. The study considered 47 794 l and a pedigree of 14 622 animals. Some practices in mating and selection management allow an increase of the inbreeding coefficient lower than 0.01 per generation in these lines of around 25 males and 125 females. Their effective population size (Ne) was around 57.3, showing that the effect of selection, increasing the inbreeding, was counterbalanced by the management practices, intended to reduce the rate of inbreeding increase. The inbreeding of each individual was broken down into three components: old, intermediate and new inbreeding. The coefficients of regression of the old, intermediate and new inbreeding on total born (TB), number born alive (NBA) and number weaned (NW) per litter showed a decreasing trend from positive to negative values. Regression coefficients significantly different from zero were those for the old inbreeding on TB (6.79 ± 2.37) and NBA (5.92 ± 2.37). The contrast between the coefficients of regression between the old and new inbreeding were significant for the three litter size traits: 7.57 ± 1.72 for TB; 6.66 ± 1.73 for NBA and 5.13 ± 1.67 for NW. These results have been interpreted as the combined action of purging unfavourable genes and artificial selection favoured by the inbreeding throughout the generations of selection.     

Estimation of inbreeding depression on female fertility in the Finnish Ayrshire population

Single nucleotide polymorphism (SNP) data enable the estimation of inbreeding at the genome level. In this study, we estimated inbreeding levels for 19,075 Finnish Ayrshire cows genotyped with a low‐density SNP panel (8K). The genotypes were imputed to 50K density, and after quality control, 39,144 SNPs remained for the analysis. Inbreeding coefficients were estimated for each animal based on the percentage of homozygous SNPs (F_PH), runs of homozygosity (F_ROH) and pedigree (F_PED). Phenotypic records were available for 13,712 animals including non‐return rate (NRR), number of inseminations (AIS) and interval from first to last insemination (IFL) for heifers and up to three parities for cows, as well as interval from calving to first insemination (ICF) for cows. Average F_PED was 0.02, F_ROH 0.06 and F_PH 0.63. A correlation of 0.71 was found between F_PED and F_ROH, 0.66 between F_PED and F_PH and 0.94 between F_ROH and F_PH. Pedigree‐based inbreeding coefficients did not show inbreeding depression in any of the traits. However, when F_ROH or F_PH was used as a covariate, significant inbreeding depression was observed; a 10% increase in F_ROH was associated with 5 days longer IFL0 and IFL1, 2 weeks longer IFL3 and 3 days longer ICF2 compared to non‐inbred cows.     

Comparison of four direct algorithms for computing inbreeding coefficients

One widely used measure in genetic analyses of livestock species is the inbreeding coefficient. Computation costs of inbreeding coefficients are of importance for large populations. Very recently, a ‘direct’ method for computing inbreeding coefficients was modified using a relatively efficient method to construct lists of ancestors in which the integrity of chronological order within each ancestral path is kept. Using simulated data, the computational efficiency of the recently modified algorithm was investigated by comparing it with three other algorithms – the original direct algorithm, its previously modified algorithm and another direct algorithm. The recently modified algorithm became considerably faster than the original algorithm and its previous modification when the number of generations increased, and it was fast relative to the other direct algorithm when the average number of generations and family size were not large. When only animals born in the most recent year were evaluated with the knowledge of inbreeding coefficients for their ancestors, the recently modified algorithm outperformed the other algorithms, indicating its possible advantage in updating situations.     

Genetic description of a divergent selection experiment in Angora rabbits with overlapping generations

The chief aims of this paper were the following: (i) to describe the demography and genetic structure in two divergent selected lines for total fleece weight (TFW) of French Angora rabbits with overlapping generations; (ii) to describe the effects of inbreeding during an experiment of divergent selection. A study of longevity with the survival kit showed that there was no significant difference in the risk of death or culling between the low line (LL) and high line (HL). A significant effect of inbreeding (p < 0.05) was observed with a 30% higher risk factor in the highest class of inbreeding coefficient compared with the other classes. The means of generation interval were 562 and 601 days in LL and HL, respectively. The numbers of generations for LL and HL were 3.90 and 3.64, respectively. Generation intervals decreased significantly from 1995 to 2000 (p < 0.05). The number of daughters in HL was very variable. The number of animals per generation was higher in HL than in LL. Each buck left nearly three daughters to the next generation (2.52 in LL, 3.24 in HL). In both lines, the effective number of ancestor genomes still present in the genetic pool of the generation was around eight from the reference population of 1995 to that of 2001. Inbreeding in HL was always higher than in LL. The effect of inbreeding was also significant (p < 0.05) on TFW and live weight. The animals with the lowest inbreeding category produced a higher TFW (p < 0.05) than the others. The observed selection differentials were lower than that expected owing to the breeding animal management rules in order to control inbreeding increase.     

On individual‐specific prediction of hidden inbreeding depression load

Inbreeding depression is caused by increased homozygosity in the genome and merges two genetic mechanisms, a higher impact from recessive mutations and the waste of overdominance contributions. It is of major concern for the conservation of endangered populations of plants and animals, as major abnormalities are more frequent in inbred families than in outcrosses. Nevertheless, we lack appropriate analytical methods to estimate the hidden inbreeding depression load (IDL) in the genome of each individual. Here, a new mixed linear model approach has been developed to account for the inbreeding depression‐related background of each individual in the pedigree. Within this context, inbred descendants contributed relevant information to predict the IDL contained in the genome of a given ancestor; moreover, known relationships spread these predictions to the remaining individuals in the pedigree, even if not contributing inbred offspring. Results obtained from the analysis of weaning weight in the MARET rabbit population demonstrated that the genetic background of inbreeding depression distributed heterogeneously across individuals and inherited generation by generation. Moreover, this approach was clearly preferred in terms of model fit and complexity when compared with classical approaches to inbreeding depression. This methodology must be viewed as a new tool for a better understanding of inbreeding in domestic and wild populations.     

闭锁群体BLUP选择下遗传方差和近交系数的变化

采用计算机随机模拟方法模拟了在一个闭锁群体内连续对单个性状进行 1 5个世代选择的情况。选择过程中世代不重叠 ,每个世代的种畜根据动物模型最佳线性无偏预测 (BLUP)法估计的育种值进行选留 ,并在此基础上系统地比较了不同群体规模、公母比例和性状遗传力对群体遗传方差和近交系数变化的影响。结果表明 ,扩大育种群规模、增加公畜比例以及对低遗传力性状进行选择时 ,群体遗传方差降低的速度和近交系数上升的速度会更慢 ,在长期选择时可望获得更大的持续进展和适宜的近交增量     

Computing inbreeding coefficients and the inverse numerator relationship matrix in large populations of honey bees

The inbreeding coefficients are considered in breeding decisions, and the inverse numerator relationship matrix A ^?1 is a prerequisite for breeding value estimation. Polyandry and haploid males are among the specifics of relationships between honey bees. Brascamp and Bijma (2014) averaged out the manifold possible relationships among honey bees that appear to have the same parents in a pedigree and assigned a single entry in A to animals that behave as a unit, for example, the workers of a hive. Their methods of calculation connected full‐sibs in the variance matrix of the Mendelian sampling terms D , via nonzero off‐diagonal elements. This impedes the inversion of A and the closely connected calculation of inbreeding coefficients, because efficient algorithms for this task take D to be a diagonal matrix. Memory limitations necessitate their use for large data sets. We adapted the quickest of them to the block diagonal matrix D , that is postulated for the honey bee. To our knowledge, the presented algorithm is the first one that facilitates the method of Brascamp and Bijma (2014) on large data sets.     

Runs of homozygosity and analysis of inbreeding depression

Pedigree information was traditionally used to assess inbreeding. The availability of high-density marker panels provides an alternative to assess inbreeding, particularly in the presence of incomplete and error-prone pedigrees. Assessment of autozygosity across chromosomal segments using runs of homozygosity (ROH) has emerged as a valuable tool to estimate inbreeding due to its general flexibility and ability to quantify the chromosomal contribution to genome-wide inbreeding. Unfortunately, the identification of ROH segments is sensitive to the parameters used during the search process. These parameters are heuristically set, leading to significant variation in the results. The minimum length required to identify an ROH segment has major effects on the estimation of inbreeding and inbreeding depression, yet it is arbitrarily set. To overcome this limitation, a search algorithm to approximate mutation enrichment was developed to determine the minimum length of ROH segments. It consists of finding genome segments with significant effect differences in trait means between animals with high and low burdens of autozygous intervals with a specific length. The minimum length could be determined heuristically as the smallest interval at which a significant signal is detected. The proposed method was tested in an inbred Hereford cattle population genotyped for 30,220 SNPs. Phenotypes recorded for six traits were used for the approximation of mutation loads. The estimated minimum length was around 1 Mb for yearling weight (YW) and average daily gain (ADG) and 4 Mb for birth weight and weaning weight. These trait-specific thresholds estimated using the proposed method could be attributed to a trait-dependent effect of homozygosity. The detection of significant inbreeding effects was well aligned with the estimated thresholds, especially for YW and ADG. Although highly deleterious alleles are expected to be more frequent in recent inbreeding (long ROH), short ROH segments (<5 Mb) could contain a large number of less deleterious mutations with substantial joint effects on some traits (YW and ADG). Our results highlight the importance of accurate estimation of the ROH-based inbreeding and the necessity to consider a trait-specific minimum length threshold for the identification of ROH segments in inbreeding depression analyses. These thresholds could be determined using the proposed method provided the availability of phenotypic information.     

Relationship between inbreeding and milk production traits in two Italian dairy sheep breeds

The effects of inbreeding in livestock species breeds have been well documented and they have a negative impact on profitability. The objective of this study was to evaluate the levels of inbreeding in Sarda (SAR, n = 785) and Valle del Belice (VdB, n = 473) dairy sheep breeds and their impact on milk production traits. Two inbreeding coefficients (F) were estimated: using pedigree (F_PED), or runs of homozygosity (ROH; F_ROH) at different minimum ROH lengths and different ROH classes. After the quality control, 38,779 single nucleotide polymorphisms remained for further analyses. A mixed-linear model was used to evaluate the impact of inbreeding coefficients on production traits within each breed. VdB showed higher inbreeding coefficients compared to SAR, with both breeds showing lower estimates as the minimum ROH length increased. Significant inbreeding depression was found only for milk yield, with a loss of around 7 g/day (for SAR) and 9 g/day (VdB) for a 1% increase of F_ROH. The present study confirms how the use of genomic information can be used to manage intra-breed diversity and to calculate the effects of inbreeding on phenotypic traits.     

The contribution of dominance and inbreeding depression in estimating variance components for litter size in Pannon White rabbits

In a synthetic closed population of Pannon White rabbits, additive (V_A), dominance (V_D) and permanent environmental (V_Pe) variance components as well as doe (b_Fd) and litter (b_Fl) inbreeding depression were estimated for the number of kits born alive (NBA), number of kits born dead (NBD) and total number of kits born (TNB). The data set consisted of 18,398 kindling records of 3883 does collected from 1992 to 2009. Six models were used to estimate dominance and inbreeding effects. The most complete model estimated V_A and V_D to contribute 5.5 ± 1.1% and 4.8 ± 2.4%, respectively, to total phenotypic variance (V_P) for NBA; the corresponding values for NBD were 1.9 ± 0.6% and 5.3 ± 2.4%, for TNB, 6.2 ± 1.0% and 8.1 ± 3.2% respectively. These results indicate the presence of considerable V_D. Including dominance in the model generally reduced V_A and V_Pe estimates, and had only a very small effect on inbreeding depression estimates. Including inbreeding covariates did not affect estimates of any variance component. A 10% increase in doe inbreeding significantly increased NBD (b_Fd = 0.18 ± 0.07), while a 10% increase in litter inbreeding significantly reduced NBA (b_Fl = ?0.41 ± 0.11) and TNB (b_Fl = ?0.34 ± 0.10). These findings argue for including dominance effects in models of litter size traits in populations that exhibit significant dominance relationships.     

Effect of sire mating patterns on future genetic merit and inbreeding in a closed beef cattle population

Summary Alternative breeding strategies were simulated based on the population structure of the Tajima strain of Japanese Black cattle. An analysis of the population structure revealed that some sires up to 20 years of age have been used in Tajima. In addition, 95% of newborn calves were the progeny of only 20 sires, and their mating frequencies were significantly skewed. The current average inbreeding coefficient and founder genome equivalents of the strain were estimated to be 0.199 and 2.25, respectively. Average inbreeding coefficient is expected to reach 0.394 within 27 years. Thus, different breeding strategies were assessed for their effect on the level of inbreeding and average genetic merit. We compared strategies that (1) halve the sire service period, (2) double the number of mating sires and (3) lower the skewed sire mating frequency and optimize the frequency for weighted genetic merit and diversity. Reducing the service period yielded a 7.0–12.0% reduction in the rate of inbreeding while maintaining almost the same genetic gain. Increasing the number of sires resulted in a 19.3–21.3% reduction in inbreeding with a corresponding 1.6–8.4% reduction in gain. The rates of inbreeding from the optimized strategies decreased as the weight on genetic diversity increased. However, a strategy that emphasized only genetic gain yielded lower gain than other strategies because the strategy allowed only one sire to mate, resulting in reduced genetic variance and low accuracy of genetic evaluation. In contrast, a strategy with no emphasis on genetic gain when determining mating frequency resulted in reductions of 16.0% and 63.2% in genetic gain and inbreeding, respectively. The strategies examined here are easily applicable and can be expected to reduce immediate loss of genetic diversity.     

Estimation of ancestral inbreeding effects on stillbirth,calving ease and birthweight in German Holstein dairy cattle

In this study, the effect of different measurements of ancestral inbreeding on birthweight, calving ease and stillbirth were analysed. Three models were used to estimate the effect of ancestral inbreeding, and the estimated regression coefficient of phenotypic data on different measurements of ancestral inbreeding was used to quantify the effect of ancestral inbreeding. The first model included only one measurement of inbreeding, whereas the second model included the classical inbreeding coefficients and one alternative inbreeding coefficient. The third model included the classical inbreeding coefficients, the interaction between classical inbreeding and ancestral inbreeding, and the classical inbreeding coefficients of the dam. Phenotypic data for this study were collected from February 1998 to December 2008 on three large commercial milk farms. During this time, 36 477 calving events were recorded. All calves were weighed after birth, and 8.08% of the calves died within 48 h after calving. Calving ease was recorded on a scale between 1 and 4 (1 = easy birth, 4 = surgery), and 69.95, 20.91, 8.92 and 0.21% of the calvings were scored with 1, 2, 3 and 4, respectively. The average inbreeding coefficient of inbred animals was 0.03, and average ancestral inbreeding coefficients were 0.08 and 0.01, depending on how ancestral inbreeding was calculated. Approximately 26% of classically non‐inbred animals showed ancestral inbreeding. Correlations between different inbreeding coefficients ranged between 0.46 and 0.99. No significant effect of ancestral inbreeding was found for calving ease, because the number of animals with reasonable high level of ancestral inbreeding was too low. Significant effects of ancestral inbreeding were estimated for birthweight and stillbirth. Unfavourable effects of ancestral inbreeding were observed for birthweight. However, favourable purging effects were estimated for stillbirth, indicating that purging could be partly beneficial for genetic improvement of stillbirth.     

Correlated response in litter size components in rabbits selected for litter size variability

A divergent selection experiment for the environmental variability of litter size (Ve) over seven generations was carried out in rabbits at the University Miguel Hernández of Elche. The Ve was estimated as the phenotypic variance within the female, after correcting for year‐season and parity‐lactation status. The aim of this study was to analyse the correlated responses to selection in litter size components. The ovulation rate (OR) and number of implanted embryos (IE) in females were measured by laparoscopy at 12 day of the second gestation. At the end of the second gestation, the total number of kits born was measured (TB). Embryonic (ES), foetal (FS) and prenatal (PS) survival were computed as IE/OR, TB/IE and TB/OR, respectively. A total of 405 laparoscopies were performed. Data were analysed using Bayesian methodology. The correlated response to selection for litter size environmental variability in terms of the litter size components was estimated as either genetic trends, estimated by computing the average estimated breeding values for each generation and each line, or the phenotypic differences between lines. The OR was similar in both lines. However, after seven generations of selection, the homogenous line showed more IE (1.09 embryos for genetic means and 1.23 embryos for phenotypic means) and higher ES than the heterogeneous one (0.07 for genetic means and 0.08 for phenotypic means). The probability of the phenotypic differences between lines being higher than zero (p) was 1.00 and .99, respectively. A higher uterine overcrowding of embryos in the homogeneous line did not penalize FS; as a result, this line continued to show a greater TB (1.01 kits for genetic means and 1.30 kits for phenotypic means, p = .99, in the seventh generation). In conclusion, a decrease in litter size variability showed a favourable effect on ES and led to a higher litter size at birth.     

Rates of inbreeding and genetic diversity in Iranian Holstein Cattle

The accumulation of inbreeding and the loss of genetic diversity is a potential problem in Holstein dairy cattle. The goal of this study was to estimate inbreeding levels and other measures of genetic diversity, using pedigree information from Iranian Holstein cattle. Edited pedigree included 1 048 572 animals. The average number of discrete generation equivalents and pedigree completeness index reached 13.4 and 90%, respectively. The rate of inbreeding was 0.3% per year. Effective number of founders, founder genomes, non‐founders and ancestors of animals born between 2003 and 2011 were 503, 15.6, 16.1 and 25.7, respectively. It was proven that the unequal founder contributions as well as bottlenecks and genetic drift were important reasons for the loss of genetic diversity in the population. The top 10 ancestors with the highest marginal genetic contributions to animals born between 2003 and 2011 and with the highest contributions to inbreeding were 48.20% and 63.94%, respectively. Analyses revealed that the most important cause of genetic diversity loss was genetic drift accumulated over non‐founder generations, which occurred due to small effective population size. Therefore, it seems that managing selection and mating decisions are controlling future co‐ancestry and inbreeding, which would lead to better handling of the effective population size.     

Assessing effective population size,coancestry and inbreeding effects on litter size using the pedigree and SNP data in closed lines of the Iberian pig breed

The complete pedigree of two closed Iberian pig lines (Gamito and Torbiscal), with 798 and 4077 reproducers, has been used to measure the evolution of coancestry (f) and inbreeding (F) for autosomal and X‐linked genes along 16 and 28 respective equivalent discrete generations. At the last generation, the mean values of each line were f = 0.41 and 0.22, F = 0.35 and 0.18, f_X = 0.46 and 0.22 and F_X = 0.47 and 0.19, respectively. Other calculated parameters were the effective number of founders (final values, 6.8 and 35.2) and non‐founders (1.5 and 2.4), founder genome equivalents (1.2 and 2.3) and effective population size (16.0 and 57.7). Measures of Torbiscal effective size based on rates of coancestry (66.1), inbreeding (65.0) and linkage disequilibrium (71.0) were estimated from whole‐genome SNP genotyping data. Values of new and old inbreeding and their respective rates by generation were computed to detect purging effects of natural selection. The analysis of 6854 Torbiscal litters showed significant negative impacts of new and fast inbreeding on litter size, as expected from the purging hypothesis: ?0.20 born piglets per litter by a 10% of new inbreeding, and ?0.03 and ?0.02 piglets by 1% of total and new inbreeding rates, respectively. The analysis performed on 1274 litters of the Gamito line failed to show purging effects. The only significant results were reductions in ?0.91 and ?0.17 piglets by a 10% of old and X‐linked genes inbreeding, respectively. These results may be useful for some practical issues in conservation programs of farm or captive wild animals.     

Application of individual increase in inbreeding to estimate realized effective sizes from real pedigrees

The objective of this study was to test the performance of a recently proposed methodology for the estimation of realized effective size (N(e)) based on individual increase in inbreeding (DeltaF(i)) on several real pedigrees: (a) an experimental mice population; (b) a closed pedigree of fighting bulls; (c) the Spanish Purebred (SPB, Andalusian) horse pedigree; (d) the Carthusian strain of SPB pedigree; (e) the Spanish Arab horse pedigree; and (f) the Spanish Anglo-Arab horse pedigree. Several reference subpopulations were defined on the basis of generation length in order to consider only animals in the last generation, to assess the influence of the pedigree content on the estimates of N(e). The estimates of realized N(e) computed from DeltaF(i) (Ne) tended to be higher than those obtained from regression on equivalent generations. The new parameter Ne remained approximately stable when pedigree depth achieved about five equivalent generations. Estimates of take into account the genetic history of the populations, the size of their founder population, and the mating policy or bottlenecks caused by poor use of reproducing individuals. The usefulness of the realized N(e) computed from individual increase in inbreeding in real pedigrees is also discussed.     

Pharmacokinetics of dexmedetomidine in isoflurane-anesthetized New Zealand White rabbits

Objective

To characterize the pharmacokinetics of dexmedetomidine when administered as a short intravenous (IV) infusion to isoflurane-anesthetized rabbits.

Genetic inbreeding depression load for fertility traits in Pura Raza Española mares

Fertility is a key factor in the economic success of horse farms. However, it has received little attention due to the difficulty of measuring fertility objectively. Since its studbook creation (1912), the Pura Raza Española (PRE) breed has been a closed population and become high in-bred resulting in inbreeding depression (poor phenotypic values). Nevertheless, heterogeneous effects of inbreeding depression have been detected among founders and nonfounders. The aims of this study were (1) to analyze the genetic parameters for reproductive traits in mares of the PRE horse breed and (2) to estimate, for the first time, the inbreeding depression load associated with common ancestors of the breed. A total of 22,799 mares were analyzed. Heritability estimates ranged from 0.05 (interval between first and second foaling) to 0.16 (age at first foaling), whereas inbreeding depression load ratios ranged from 0.06 (parturition efficiency at 6th foaling) to 0.17 (age at first foaling), for a partial inbreeding coefficient of 10%. Although heritability is related to the variability expressed in the population, inbreeding depression load ratios measure the potential variability, whether expressed in the population or not. Most correlations between additive and inbreeding depression load genetic values were significant (P < 0.001) and of low to moderate magnitude. Our results confirm that individual inbreeding depression loads allow us to select horses that have a genetic value resistant to the deleterious effects of inbreeding.     

Role of selection and inbreeding on the incidence of cutaneous malignant melanoma in Sinclair swine

Summary This paper reports the quantitative analysis of the historical database of a herd of Sinclair swine affected by cutaneous malignant melanoma. The herd was under partial and non-systematic selection for melanoma susceptibility (animals having at least one tumour during the first 6 weeks of life). Weighted selection differentials for the number of tumours at birth and the number of tumours at 6 weeks were generally positive and between −0.43 and 4.76 tumours for the number of tumours at 6 weeks. Estimates of the heritability for number of tumours at birth and at 6 weeks using 1934 animals were 0.27 (±0.03) and 0.25 (±0.03), respectively. The estimate of the genetic correlation between these two traits was 0.95 (±0.03). Genetic trends were positive for the number of tumours at birth and at 6 weeks. In spite of positive selection differentials and a moderate heritability, there was a negative phenotypic trend in the number of tumours. Natural selection might be acting in a direction opposite to artificial selection in the Sinclair herd. The slopes of the regression of the number of tumours at birth, at 6 weeks, and melanoma susceptibility on individual inbreeding coefficients were non-significant, indicating no evidence of dominance. The number of live-born pigs was lower in litters from parents susceptible to the disease (p < 0.01).