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Genetic determinants of severity of acute withdrawal from diazepam in mice: commonality with ethanol and pentobarbital.

Potentially life-threatening seizures can occur following withdrawal from benzodiazepines, ethanol, or barbiturates. In animals, withdrawal severity has been shown to be partially genetically determined for each drug class. Susceptibility to these drugs is partially determined by common genetic factors, but the evidence is conflicting. We tested the hypothesis that acute benzodiazepine withdrawal convulsions are influenced by at least some genes that also affect withdrawal from ethanol and pentobarbital. Results in inbred mouse strains demonstrate that strain susceptibility is genetically correlated with susceptibility to ethanol and pentobarbital. The proportion of variance accounted for by genetic factors common to diazepam and ethanol was estimated at 69%. Results contrast with previous data obtained in mice that were serially tested for withdrawal severity from ethanol, pentobarbital, and then diazepam, because serial testing of mice significantly affected the previous results for some strains. Diazepam withdrawal severity was also genetically correlated with pentobarbital withdrawal. Together, these results suggest that some genes influence severity of withdrawal from several types of depressant drugs.

Animals↗

Genetic antagonism between body weight and milk production in beef cattle.

Korean cattle have an unusually short suckling period (4 mo) due to poor milking ability, and this is a hindrance to growth of calves. Therefore, Korean cattle breeders have shown interest in genetic improvement of milking ability. In this study, body weight (birth weight, weaning weight, and yearling weight) and five daily milk yields by period in Korean cattle (Hanwoo) were analyzed using a two-trait sire and maternal grandsire mixed model. The milk yields used were actually measured at sequential intervals from 1 to 4 mo after calving. Posterior means of the parameters were estimated using Gibbs sampling. Heritability estimates (0.25 to 0.26) for daily milk yield at weaning were larger than those with other periods. Genetic impact on daily milk yield, especially at weaning, was emphasized in order to lengthen the suckling period of Korean cattle. Genetic correlation estimates between BW and daily milk yield were all negative (-0.08 to -0.16 for birth weight, -0.04 to -0.21 for weaning weight, and -0.12 to -0.19 for yearling weight), whereas environmental correlation estimates were all positive (0.20 to 0.39 for birth weight, 0.34 to 0.51 for weaning weight, and 0.30 to 0.45 for yearling weight). The negative estimates of genetic correlation between weight and milk yield implied genetic antagonism between direct and maternal effects for weaning weight of beef cattle.

Animals↗

Evolutionary genetics of juvenile hormone and ecdysteroid regulation in Gryllus: a case study in the microevolution of endocrine regulation.

During the past 15 years the first detailed synthesis of endocrinology and population genetics has begun, in which natural genetic variations for endocrine regulators have been characterized, almost exclusively in species of the cricket genus Gryllus. Artificial selection studies have documented that regulators of the juvenile hormone titer can rapidly evolve and exhibit levels of genetic variability similar to other physiological traits. Strong genetic correlations exist between some but not all regulators of the JH titer during the juvenile stage. No genetic correlation exists between regulators functioning in juvenile and adult stages, and thus, endocrine regulation can evolve independently in these stages. Genetic variation in the JH titer, the ecdysteroid titer, and JHE activity, in adult and juvenile stages, have been documented in genetic stocks of wing-polymorphic crickets; morph-specific differences in these endocrine traits are potentially responsible for genetically based differences in aspects of wing and flight muscle development, adult egg production, and adult dispersal. An unexpected morph-specific, genetic polymorphism for a circadian rhythm for the JH titer was observed in both the laboratory and field. Few comparable studies exist in non-Gryllus species, in which in vivo endocrine-genetic variation has been directly quantified using reliable analytical methods; many reported cases of endocrine variation in these species have been obtained using an inappropriate method and thus should be considered unsubstantiated. Obtaining basic information on the characteristics of natural genetic variation for endocrine regulators still remains one of the most important tasks of the fledgling subdiscipline of evolutionary endocrinology. Single gene endocrine mutants in Drosophila are promising candidates for investigating molecular-genetic variation in natural populations. Future studies should also focus on endocrine traits studied in the field and geographic variation in endocrine regulation.

Animals↗

Genetic parameters for milk production and persistency for Danish Holsteins estimated in random regression models using REML.

(Co)variance components for milk, fat, and protein yield of 8075 first-parity Danish Holsteins (DH) were estimated in random regression models by REML. For all analyses, the fixed part of the model was held constant, whereas four different functions were applied to model the additive genetic effect and the permanent environment effect. Homogeneous residual variance was assumed throughout lactation. Univariate models were compared using a minimum of -2 ln(restricted likelihood) as the criterion for best fit. Heritabilities as a function of time were calculated from the estimated curve parameters from univariate analyses. Independent of the function applied and the trait in question, heritabilities were lowest in the beginning of the lactation. Heritabilities for persistency of fat yield were slightly higher than heritabilities for persistency of milk and protein yield. Genetic correlations between persistency and 305-d production were higher for protein and milk yield than for fat yield. Bivariate analyses between the production traits were carried out in sire models using the models with the best 3-parameter curve fit in the univariate analyses. Correlations between traits were calculated from covariance components for curve parameters estimated in bivariate analyses. Genetic correlations between milk and protein yield were higher than between milk and fat yield.

Algorithms↗

Genetic parameters for direct and maternal calving ability over parities in Piedmontese cattle.

Estimates of heritabilities and genetic correlations for calving ease over parities were obtained for the Italian Piedmontese population using animal models. Field data were calving records of 50,721 first- and 44,148 second-parity females and 142,869 records of 38,213 cows of second or later parity. Calving ability was scored in five categories and analyzed using either a univariate or a bivariate linear model, treating performance over parities as different traits. The bivariate model was used to investigate the genetic relationship between first- and second- or between first- and third-parity calving ability. All models included direct and maternal genetic effects, which were assumed to be mutually correlated. (Co)variance components were estimated using restricted maximum likelihood procedures. In the univariate analyses, the heritability for direct effects was .19 +/- .01, .10 +/- .01, and .08 +/- .004 for first, second, and second and later parities, respectively. The heritability for maternal effects was .09 +/- .01, .11 +/- .01, and .05 +/- .01, respectively. All genetic correlations between direct and maternal effects were negative, ranging from -.55 to -.43. Approximated standard errors of genetic correlations between direct and maternal effects ranged from .041 to .062. For multiparous cows, the fraction of total variance due to the permanent environment was greater than the maternal heritability. With bivariate models, direct heritability for first parity was smaller than the corresponding univariate estimate, ranging from .18 to .14. Maternal heritabilities were slightly higher than the corresponding univariate estimates. Genetic correlation between first and second parity was .998 +/- .00 for direct effects and .913 +/- .01 for maternal effects. When the bivariate model analyzed first- and third-parity calving ability, genetic correlation was .907 +/- .02 for direct effects and .979 +/- .01 for maternal effects. Residual correlations were low in all bivariate analyses, ranging from .13 for analysis of first and second parity to .07 for analysis of first and third parity. In conclusion, estimates of genetic correlations for calving ease in different parities obtained in this study were very high, but variance components and heritabilities were clearly heterogeneous over parities.

Animals↗

Genetic analysis of growth traits in Muzaffarnagari sheep.

Data on 4112 Muzaffarnagari sheep, maintained at the Central Institute for Research on Goats, Makhdoom, Mathura, India, and recorded between 1976 and 1999, were analysed to study the growth-related traits and their genetic control. The average weights at birth, and at 12 months of age were 3.1 +/- 0.2 and 28.0 +/- 0.6 kg, respectively. The pre- and post-weaning average daily weight gains were 127.8 +/- 3.3 g and 49.4 +/- 1.6 g. and the associated growth efficiencies were 3.59 +/- 0.08 and 0.95 +/- 0.03. Significant differences associated with the year of lambing were observed in body weight, weight gain and efficiency in weight gain at different stages of growth. The lambs born in the dam's second parity were generally of heavier weight and higher daily weight gain than those born in other parities. Males were heavier and had a higher weight gain than females at almost all stages of growth and the differences tended to increase with age. Single-born lambs had a distinct advantage over those born in multiple births at all stages of growth. The heritabilities of all body weights, weight gains and efficiency in weight gains at different stages of growth were moderate (0.18-0.26), except for birth weight, which was of low heritability (0.068 +/- 0.01). The phenotypic and genetic correlations among the different body weights were positive and high, except for birth weight. The genetic correlation of the pre- and post-weaning average daily weight gains with body weights were high and positive.

Animal Husbandry↗

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

Female↗

Genetic analysis of Holstein cattle populations in Brazil and the United States.

Genetic relationships between Brazilian and US Holstein cattle populations were studied using first-lactation records of 305-d mature equivalent (ME) yields of milk and fat of daughters of 705 sires in Brazil and 701 sires in the United States, 358 of which had progeny in both countries. Components of(co)variance and genetic parameters were estimated from all data and from within herd-year standard deviation for milk (HYSD) data files using bivariate and multivariate sire models and DFREML procedures distinguishing the two countries. Sire (residual) variances from all data for milk yield were 51 to 59% (58 to 101%) as large in Brazil as those obtained from half-sisters in the average US herd. Corresponding proportions of the US variance in fat yield that were found in Brazil were 30 to 41% for the sire component of variance and 48 to 80% for the residual. Heritabilities for milk and fat yields from multivariate analysis of all the data were 0.25 and 0.22 in Brazil, and 0.34 and 0.35 in the United States. Genetic correlations between milk and fat were 0.79 in Brazil and 0.62 in the United States. Genetic correlations between countries were 0.85 for milk, 0.88 for fat, 0.55 for milk in Brazil and fat in the US, and 0.67 for fat in Brazil and milk in the United States. Correlated responses in Brazil from sire selection based on the US information increased with average HYSD in Brazil. Largest daughter yield response was predicted from information from half-sisters in low HYSD US herds (0.75 kg/kg for milk; 0.63 kg/kg for fat), which was 14% to 17% greater than estimates from all US herds because the scaling effects were less severe from heterogeneous variances. Unequal daughter response from unequal genetic (co)variances under restrictive Brazilian conditions is evidence for the interaction of genotype and environment. The smaller and variable yield expectations of daughters of US sires in Brazilian environments suggest the need for specific genetic improvement strategies in Brazilian Holstein herds. A US data file restricting daughter information to low HYSD US environments would be a wise choice for across-country evaluation. Procedures to incorporate such foreign evaluations should be explored to improve the accuracy of genetic evaluations for the Brazilian Holstein population.

Animals↗

Behavioral responses to novelty and structural variation of the hippocampus in mice. II. Multivariate genetic analysis.

On the basis of results from lesion studies in rodents, covariations are expected to exist between naturally-occurring heritable variations in hippocampal morphology and exploratory behavior elicited by novel surroundings. For this reason, we set up a full diallel cross between five inbred mouse strains and analyzed the behavioral and the hippocampal anatomical variation in male animals from this cross. Employing a bivariate extension of the diallel-cross analysis, estimates were obtained for the phenotypical, environmental, and genetical correlations between the phenotypes studied. A factor analysis performed on the matrix of additive-genetic correlations revealed that variations in the size of the intra- and infrapyramidal mossy fiber terminal fields (iip-MF) are negatively related to open-field exploration and novelty-induced fear. These results indicate that having larger iip-MF projections promotes the collection and processing of information about a novel environment, entailing lower levels of exploration and fear.

Animals↗

Genetic linkage of ecological specialization and reproductive isolation in pea aphids.

The evolution of ecological specialization generates biological diversity and may lead to speciation. Genetic architecture can either speed or retard this process. If resource use and mate choice have a common genetic basis through pleiotropy or close linkage, the resulting genetic correlations can promote the joint evolution of specialization and reproductive isolation, facilitating speciation. Here we present a model of the role of genetic correlations in specialization and speciation, and test it by analysing the genetic architecture of key traits in two highly specialized host races of the pea aphid (Acyrthosiphon pisum pisum; Hemiptera : Aphididae). We found several complexes of pleiotropic or closely linked quantitative trait loci (QTL) that affect key traits in ways that would promote speciation: QTL with antagonistic effects on performance on the two hosts are linked to QTL that produce asortative mating (through habitat choice). This type of genetic architecture may be common in taxa that have speciated under divergent natural selection.

Adaptation, Biological↗

Genetic and phenotypic relationships of farrowing and weaning survival to birth and placental weights in pigs.

Data obtained during 4 generations of divergent selection for placental efficiency were used to determine factors influencing survival at farrowing and weaning in litters produced by first-parity females. Data were collected from 193 litters and included records on 2,053 individuals. Farrowing survival (FS) and weaning survival (WS) were considered traits of the piglet and were scored 1 if the individual was alive at a time point or 0 if dead. Estimates of (co)variance components for direct and maternal additive genetic effects for FS and WS were obtained using an animal model and computed with the MTDFREML program. Estimates of direct heritability were 0.16 for FS and 0.18 for WS. Estimates of maternal heritability were 0.14 for FS and 0.10 for WS. Genetic correlation estimates between direct and maternal effects were high and negative for both traits. The direct genetic correlation between FS and WS was 0.92. Variables associated with FS and WS were determined using logistic regression procedures. Birth weight (BRW), placental weight, their interaction, and total born can be used as predictors of survival at farrowing in the absence of estimates of genetic merit for survival. The same model, excluding total number born, was the best model for predicting WS. In the presence of BRW information, placental efficiency did not improve the prediction of survival. While it was clearly disadvantageous for a piglet to be below the litter mean in BRW, being above the mean did not provide a substantial advantage in survival. Results from this analysis suggest that it is possible to select for increased survival at farrowing and at weaning. Information on a piglet's BRW, placental weight, litter average BRW, and deviation from litter average BRW can be used to optimize those values at levels resulting in high survival probability.

Animals↗

Carbon isotope discrimination and oxygen isotope composition in clones of the F(1) hybrid between slash pine and Caribbean pine in relation to tree growth, water-use efficiency and foliar nutrient concentration.

The objectives of this study were: (1) to examine how foliar carbon isotope discrimination (Delta) and oxygen isotope composition (delta(18)O) are related to tree growth, ash mineral nutrient concentration and foliar nutrient concentration in 7-year-old clones of the F(1) hybrid between slash pine (Pinus elliottii Engelm.) and Caribbean pine (P. caribaea var. hondurensis Barr. et Golf.) in subtropical Australia; and (2) to evaluate the potential of using foliar Delta, ash mineral nutrient concentration and delta(18)O measurements for selecting F(1) hybrid pine clones with high water-use efficiency (WUE) and growth potential. There were significant differences in tree growth, foliar Delta, delta(18)O and ash mineral nutrient concentration among the eight clones tested. Significant negative linear relationships existed between tree growth and Delta, extrapolating to zero growth at Delta = 24-30 per thousand. There were strong genetic correlations (r = -0.83 to -0.96) between Delta and tree growth, particularly tree height. Significant non-genetic correlations (r = -0.62 to -0.80) existed between Delta and foliar K concentration. Foliar delta(18)O, ash mineral nutrient concentration and foliar nutrient concentration were unrelated to tree growth. In the F(1) hybrid pine clones, variation in tree WUE, as reflected by Delta, was largely attributed to a genetic effect on leaf photosynthetic capacity rather than on stomatal conductance, as reflected by foliar delta(18)O.

Journal Article↗

Teat scores in first-parity Gelbvieh cows: relationship with suspensory score and calf growth traits.

Teat and udder suspensory scores from 9,418 first-parity Gelbvieh cows and growth records from 19,119 calves were used to estimate genetic and environmental parameters for teat and suspensory score and to investigate the relationship of teat and suspensory score with calf growth traits and maternal genetic growth effects. First-parity cows did not have multiple records within 280 d, gave birth to one calf, were 4 yr of age or younger at first-calving, and were at least 50% Gelbvieh. Producers scored cows within 24 h of parturition. Teat score (T), a subjective measure of teat size, ranged from 0 (very large) to 50 (very small), and suspensory score (S), a subjective score of udder support, ranged from 0 (very pendulous) to 50 (very tight). Unadjusted birth weight (BW), weaning weight, and yearling weight of the calves, born in the first three parities to cows with first-parity T and S records, were used to calculate pre- and postweaning ADG (WG and YG, respectively). A mixed model was used for the multiple trait analysis of T, S, BW, WG, and YG, which included herd-year, month of calving, age of cow at calving, and sex of calf (included only for BW, WG, and YG) as systematic effects; regression on the percentage of Gelbvieh; and additive animal and maternal genetic of dam (included only for BW and WG), maternal permanent environment (included only for BW and WG), and residual as random effects. The genetic correlation between T and S was 0.95, suggesting that T and S are basically the same trait in this dataset. The genetic correlations between T (S) with direct BW, WG, and YG and with maternal BW and WG were -0.18 (-0.06), 0.38 (0.31), 0.09 (-0.01), -0.16 (-0.16), and -0.47 (-0.55), respectively, suggesting that cows with smaller teats and tighter udders produced less milk and raised calves that had higher genetic growth potential for WG. Further, the Pearson correlations between predicted breeding values of T and S with maternal WG indicated that animals with extremely large teats or pendulous udders may produce more milk, but that the calf may have trouble accessing it. Conversely, with extremely small teats or tight udders, smaller amounts of milk would be produced and there may be a problem producing enough milk to maintain the growing calfs maintenance requirements. Therefore, it may be more beneficial for producers to select animals that have intermediate breeding values for T and S.

Age Factors↗

Genetic relationships between calving interval and body condition score conditional on milk yield.

Body condition score (BCS) is a useful tool in assessing the energy status of dairy cattle. Previous research has shown that it is heritable and genetically correlated to reproductive performance. Currently, interest exists in developing selection indexes for fertility that include BCS information. Before such indexes are developed, it is important to assess the genetic covariance between BCS and fertility after fully accounting for the covariance of both traits with milk yield, as indices to predict selection responses require knowledge of these (co)variances. In the present study, calving interval (CI) was used as a measure of reproductive performance. The genetic correlations between BCS and CI before and after genetically adjusting for milk yield were -0.48 and -0.22, respectively. Thus, cows with low BCS have longer CI, which is exacerbated by high levels of milk production. Using selection index theory, we showed that selecting for milk yield alone will result in an increase of 768 kg of milk, an increase of 4.46 d in CI and a reduction of 0.41 BCS units for every standard deviation change in the index. Restricting BCS to no genetic change, whereas still selecting for milk yield will result in an increase of 653.1 kg of milk per standard deviation of the selection index. However, CI will still continue to increase at a rate of 3.20 d per standard deviation of the selection index. The selection indices used here are not optimum, in that they are not economically driven and do not consider all traits that contribute to profitability. However, they demonstrate that, even though restricting BCS may be seen as an attractive way of limiting reliance of body tissue mobilization to fuel milk production, this is unlikely to result in improvements in CI, although the rate of increase in CI will be reduced.

Analysis of Variance↗

Direct and correlated responses to artificial selection on developmental time and wing length in Drosophila buzzatii.

Developmental time and body size are two positively correlated traits closely related to fitness in many organisms including Drosophila. Previous work suggested that these two traits are involved in a trade-off that may result from a negative genetic correlation between their effects on pre-adult and adult fitness. Here, we examine the evolution of developmental time and body size (indexed by wing length) under artificial selection applied to one or both traits in replicated D. buzzatii populations. Directional changes in both developmental time and wing length indicate the presence of substantial additive genetic variance for both traits. The strongest response to selection for fast development was found in lines selected simultaneously to reduce both developmental time and wing length, probably as an expected consequence of a synergistic effect of indirect selection. When selection was applied in the direction opposite to the putative genetic correlation, that is, large wing length but fast development, no responses were observed for developmental time. Lines selected to reduce both wing length and developmental time diverged slightly faster from the control than lines selected to increase wing length and reduce developmental time. However, wing length did not diverge from the control in lines selected only for fast development. These results suggest a complex genetic basis of the correlation between developmental time and wing length, but are generally consistent with the hypothesis that both traits are related in a trade-off. However, we found that this trade-off may disappear under uncrowded conditions, with fast-developing lines exhibiting a higher pre-adult viability than other lines when tested at high larval density.

Analysis of Variance↗

Selection and genetic (co)variance in bighorn sheep.

Genetic theory predicts that directional selection should deplete additive genetic variance for traits closely related to fitness, and may favor the maintenance of alleles with antagonistically pleiotropic effects on fitness-related traits. Trait heritability is therefore expected to decline with the degree of association with fitness, and some genetic correlations between selected traits are expected to be negative. Here we demonstrate a negative relationship between trait heritability and association with lifetime reproductive success in a wild population of bighorn sheep (Ovis canadensis) at Ram Mountain, Alberta, Canada. Lower heritability for fitness-related traits, however, was not wholly a consequence of declining genetic variance, because those traits showed high levels of residual variance. Genetic correlations estimated between pairs of traits with significant heritability were positive. Principal component analyses suggest that positive relationships between morphometric traits constitute the main axis of genetic variation. Trade-offs in the form of negative genetic or phenotypic correlations among the traits we have measured do not appear to constrain the potential for evolution in this population.

Age Factors↗

Estimation of genetic parameters for test day records of somatic cell score.

The present study estimated variance components for test day records of somatic cell score and production traits. Data consisted of 235,100 test day observations recorded between 1986 and 1994 on lactations 1 to 3 of 15,922 Holstein cows from 143 herds. Records were considered as repeated observations within a lactation and as different traits across lactations. The multiple-trait animal model for analysis included random animal additive genetic and permanent environment effects by lactation. Fixed effects included herd test date and a set of four covariables for days in lactation, estimated by parity, age, and season, which accounted for the shape of the lactation curve. Gibbs sampling chains were carried out separately for somatic cell score and milk production and fat and protein yields. Heritabilities of somatic cell score for lactations 1 to 3 were .09, .09, and .11, respectively. Genetic correlations between lactations were high (.88, .79, and .95 between lactations 1 and 2, 1 and 3, and 2 and 3, respectively). Correlations between permanent environment effects were smaller (.29, .19, and .46 between lactations 1 and 2, 1 and 3, and 2 and 3, respectively). Heritabilities and correlations between permanent environment effects were higher for production traits than for somatic cell score. Genetic correlations between lactations for production traits were similar to those for somatic cell score. Variances between lactations differed significantly, indicating that observations from different lactations should no be considered as repeated observations of the same trait.

Animals↗

Application of the covariance function approach with an iterative two-stage algorithm to the estimation of parameters of a random regression test day model for dairy production traits.

The covariance function approach with an iterative two-stage algorithm of LIU et al. (2000) was applied to estimate parameters for the Polish Black-and-White dairy population based on a sample of 338 808 test day records for milk, fat, and protein yields. A multiple trait sire model was used to estimate covariances of lactation stages. A third-order Legendre polynomial was subsequently fitted to the estimated (co)variances to derive (co)variances of random regression coefficients for both additive genetic and permanent environment effects. Daily and 305-day heritability estimates obtained are consistent with several studies which used both fixed and random regression test day models. Genetic correlations between any two days in milk (DIM) of the same lactation as well as genetic correlations between the same DIM of two lactations were within a biologically acceptable range. It was shown that the applied estimation procedure can utilise very large data sets and give plausible estimates of (co)variance components.

Journal Article↗