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Genome-wide analysis of screen behaviors among adolescents identifies novel loci and overlap with educational attainment and mental disorders.

Technological devices play a central role in adolescents' life. Despite concerns about negative effects of excessive screen time, there is little knowledge of screen behaviors' genetic architecture. Using self-reports from adolescents in the Norwegian Mother, Father, and Child Cohort Study (n = 18,490), we performed genome-wide association analysis for four screen behaviors: time spent (1) watching television; (2) gaming; (3) sitting/lying down with a screen device; and (4) using social media. The resulting summary statistics were analysed using the conditional false discovery rate (condFDR) approach to increase genetic discovery. We also estimated SNP-heritabilities of the screen behaviors and genetic correlations with eight psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit hyperactivity disorder, anorexia nervosa, cannabis use disorder and alcohol use disorder), and educational attainment. Screen behaviors displayed significant SNP-heritabilities (0.048-0.12). We observed significant genetic correlations between screen behaviors and psychiatric disorders (rg range: 0.21-0.42). Educational attainment demonstrated negative genetic correlation with screen behaviors, most strongly with social media use (rg = - 0.69). CondFDR analysis identified three novel loci associated with social media use. Thus, we show that screen behaviors are heritable, polygenic traits that partly share genetic signal with mental disorders and educational attainment.

Humans↗

Genetic parameters for litter size in sheep: natural versus hormone-induced oestrus.

The litter size in Suffolk and Texel-sheep was analysed using REML and Bayesian methods. Litters born after hormonal induced oestrus and after natural oestrus were treated as different traits in order to estimate the genetic correlation between the traits. Explanatory variables were the age of the ewe at lambing, period of lambing, a year*flock-effect, a permanent environmental effect associated with the ewe, and the additive genetic effect. The heritability estimates for litter size ranged from 0.06 to 0.13 using REML in bi-variate linear models. Transformation of the estimates to the underlying scale resulted in heritability estimates from 0.12 to 0.17. Posterior means of the heritability of litter size in the Bayesian approach with bi-variate threshold models varied from 0.05 to 0.18. REML estimates of the genetic correlations between the two types of litter size ranged from 0.57 to 0.64 in the Suffolk and from 0.75 to 0.81 in the Texel. The posterior means of the genetic correlation (Bayesian analysis) were 0.40 and 0.44 for the Suffolk and 0.56 and 0.75 for the Texel in the sire and animal model respectively. A bivariate threshold model seems appropriate for the genetic evaluation of prolificacy in the breeds concerned.

Animals↗

Genetic aspects of communication during male-male competition in the Madagascar hissing cockroach: honest signalling of size.

Male Madagascar hissing cockroaches, Gromphadorhina portentosa, engage in agonistic contests with other males and produce audible sounds or 'hisses' during these interactions. Hisses are used to maintain, rather than to establish, social relationships among males. The agonistic hisses of males are variable and could be used as signals to communicate size or competitive ability of an individual. In this study we examined how size influences male-male competition, as well as the genetic variation and covariation of male body size and components of the agonistic hiss. We found that male size affected the outcome of agonistic interactions between pairs of males: a male that dominated in a pair was significantly larger than the male that was subordinate. However, we found no differences in the hisses produced by dominant and subordinate males after controlling for male weight. We estimated heritabilities, evolvability and genetic correlations for male size and characteristics of the hiss from a full-sib analysis of brothers. The patterns of heritabilities and evolvabilities were very similar. The heritabilities of both male weight and duration of the hiss were significantly greater than zero. There was a significant positive genetic correlation between duration of the agonistic hiss and male weight, and a significant negative genetic correlation between hiss duration and the beginning dominant frequency. There was also a positive phenotypic correlation and a negative environmental correlation between male weight and hiss duration. Thus, hiss duration can signal the present influence of the environment on male size, whereas information from hiss duration and beginning dominant frequency can signal the male's ability to transmit genetic influence for size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inverse correlation between genetic aberrations and malignancy grade in ependymal tumors: a paradox?

OBJECTIVE: The goal of our study was to investigate the inverse correlation between number of genetic aberrations and malignancy grade in ependymal tumors at the ploidy level. METHODS: we examined seven myxopapillary ependymomas (mpEs) (WHO grade I), 28 spinal and cerebral ependymomas (Es) (WHO grade II), and 18 cerebral anaplastic ependymomas (aEs) (WHO grade III) using image DNA cytometry. The ploidy status was correlated with clinicopathological characteristics and with the results obtained by comparative genomic hybridization (CGH) analysis that we performed in about half of these tumors. RESULTS: mpEs were exclusively located in the spinal cord and aEs in the cerebrum only, whereas Es were located in both the spinal cord and brain. We found aneuploidy or tetraploidy to be common in the group of mpEs (6 out of 7) and much less frequent in Es (6 out of 28) and aEs (4 out of 18). Three-year postoperative survival was 100% for mpEs, 100% for spinal Es, 92% for cerebral Es, and 33% for aEs. Our CGH results in a selection of these tumors revealed the highest number of genetic aberrations in the mpEs (average 16; n = 2), a lower number in Es (average 12; n = 11) and the lowest number in aEs (average 5; n = 6). Interestingly, in the group of Es and aEs, a high number of genetic aberrations as detected by CGH was not correlated with aneuploidy or tetraploidy. Three patients, all with mpEs had local seeding. CONCLUSION: These results underline that mpEs are distinctly different from Es and aEs at the genetic level and that extensive genomic alterations and aneuploidy in ependymal tumors are not in itself an indicator of malignant behavior.

Adolescent↗

Response to long-term selection for egg production in laying hens.

1. A White Leghorn line was selected for part-record hen-housed number of eggs from 1962 to 1990. Genetic changes were estimated as deviations from its unselected control line. 2. Over the first 10 generations with selection almost exclusively for number of eggs to the age of 273 d, all traits, except rate of mortality, showed significant changes. Regressions per year were: 273 d production, 3.07 eggs; 497 d production, 5.18 eggs; production from 274 to 497 d, 2.43 eggs; age at first egg, -2.33 d; mean weight of first 10 eggs, -0.82 g; body weight at 497 d, -19.02 g and rate of mortality, 0.19%. 3. Over the rest of the period increasing selection pressure for egg weight has been applied. This resulted in positive changes for this trait and no or small negative changes in egg number. 4. In general, heritabilities and genetic correlations did not change over the period of selection. The heritability of the main trait of selection, production to 273 d was 0.19 +/- 0.04 and heritabilities of egg size traits about 0.50. 5. The genetic correlation between egg production to 273 d and mean weight of first 10 eggs was estimated as -0.37 +/- 0.06 but from the observed response a realised genetic correlation of -0.97 was calculated.

Aging↗

Bayesian estimates of covariance components between lactation curve parameters and disease liability in Danish Holstein cows.

In the present work, covariance components for milk yield and disease liability were estimated with bivariate random regression test-day sire models using a Bayesian approach and implemented via the Gibbs sampler. The data consist of 8075 first-parity Danish Holstein (DH) cows, from 1259 sires, performing in 57 herds from 1992 to 1997. Treatments associated with five different type of diseases were pooled into a single general disease liability for each cow. Two models were fitted to the data. First, using a bivariate model, milk yield is modeled via a random regression, and disease liability via a repeatablility model. Second, using a bivariate model, both milk yield and disease liability are modeled using random regressions. A comparison based on a Bayes factor provides very strong support for the bivariate random regression model. Posterior means of heritabilities for each of the traits were estimated for five different points in time throughout lactation. Across models, heritabilities for milk yield are lowest in the beginning of the lactation (0.19) and highest at the end of the lactation (0.35). Posterior means of heritabilities of disease liability range from 0.04 to 0.10 for test days, and is equal to 0.20 for the whole lactation. Heritability of persistency measures estimated from the two models are 0.20 and 0.21. Estimates of posterior means of genetic correlations between single test-day milk yield and single test-day disease liability are in the range of 0.31 to 0.57. The estimates of posterior mean and of the 95% posterior interval of the genetic correlation between persistency and (total) disease liability using the model with the highest posterior probability are -0.12 and (-0.44; 0.20), respectively. Even though the largest proportion of the posterior probability mass is spread along negative values of the correlation (indicating that individuals with a flatter lactation curve tend to have lower disease liability), a value of zero of the genetic correlation falls comfortably within the 95% posterior interval. Thus the prospects of reducing incidence of disease by manipulating persistency as defined in this work remain inconclusive.

Animals↗

Random regression models for male and female fertility evaluation using longitudinal binary data.

A longitudinal Bayesian threshold analysis of insemination outcomes was carried out using 2 random regression models with 3 (Model 1) and 5 (Model 2) parameters to model the additive genetic values at the liability scale. All insemination events of first-parity Holstein cows were used. The outcome of an insemination event was treated as a binary response of either a success (1) or a failure (0). Thus, all breeding information for a cow, including all service sires, was included, thereby allowing for a joint evaluation of male and female fertility. An edited data set of 369,353 insemination records from 210,373 first-lactation cows was used. On the liability scale, both models included the systematic effects of herd-year, month of insemination, technician, and regressions on age of service sire and milk yield during the first 100 d of lactation. The random effects in the model were the 3 or 5 random regression coefficients specific to each cow, the permanent effect of the cow, and the service sire effect. Using Model 1, the estimated heritability of an insemination outcome decreased from 0.035 at d 50 to 0.032 at d 140 and then increased continuously with DIM. The genetic correlations for insemination success at different time points ranged from 0.83 to 0.99, and their magnitude decreased with an increase in the interval between inseminations. A similar trend was observed for heritability and genetic correlations using Model 2. However, the average estimate of heritability was much higher (0.058) than those obtained using Model 1 or a repeatability model. In addition, the estimated genetic correlations followed the same trend as Model 1, but were lower and with a higher rate of decrease when the interval between inseminations increased. The posterior mean of service sire variance was 0.01 for both models, and permanent environmental variance was 0.05 and 0.02 for Models 1 and 2, respectively. Model comparison based on the Bayes factor indicated that Model 1 was more plausible, given the data.

Animals↗

Autosomal dominant polycystic kidney disease-type 2. Ultrasound, genetic and clinical correlations.

BACKGROUND: Ultrasound, genetic and clinical correlations are available for ADPKD-1, but lacking for ADPKD-2. The present study was carried out to address: (i) the age-related diagnostic usefulness of ultrasound compared with genetic linkage studies; (ii) the age-related incidence and prevalence of relevant symptoms and complications; and (iii) the age and causes of death in patients with ADPKD-2. METHODS: Two hundred and eleven alive subjects, from three ADPKD-2 families at 50% risk, were evaluated by physical examination, consultation of hospital records, biochemical parameters, ultrasound and with genetic linkage and DNA mutation analyses. Nineteen deceased and affected family members were also included in the study. RESULTS: Of the 211 alive members, DNA linkage studies and direct mutation analyses showed that 106 were affected and 105 were not. Ultrasound indicated 94 affected, 108 not affected and nine equivocal results in nine children under the age of 15. For all ages, the false-positive diagnostic rate for ultrasound was 7.5% and the false-negative rate was 12.9%. The difference between ultrasound and DNA findings was most evident in children aged 5-14 years where the ultrasound was correct in only 50% and wrong or inconclusive in the remaining 50%. The mean age of the 106 alive, ADPKD-2 genetically affected patients was 37.9 years (range: 6-66 years). Among them, 23.5% had experienced episodes of renal pain, 22.6% were treated for hypertension, 22.6% had experienced at least one urinary tract infection, 19.8% had nephrolithiasis, 11.3% had at least one episode of haematuria, 9.4% had asymptomatic liver cysts, 7.5% had developed chronic renal failure and 0.9% had reached end-stage renal failure. Of the 19 deceased members, nine died before reaching end-stage renal failure at a mean age of 58.7 years (range: 40-68 years), mainly due to vascular complications, while the remaining 10 died on haemodialysis at a mean age of 71.4 years (range: 66-82 years). CONCLUSIONS: DNA analysis is the gold standard for the diagnosis of ADPKD-2, especially in young people. Ultrasound diagnosis is highly dependent on age. Under the age of 14, ultrasound is not recommended as a routine diagnostic procedure, but ultrasound becomes 100% reliable in excluding ADPKD-2 in family members at 50% risk, over the age of 30. ADPKD-2 represents a mild variant of polycystic kidney disease with a low prevalence of symptoms and a late onset of end-stage renal failure.

Acute Kidney Injury↗

Genetic analysis of milk production traits of polish black and white cattle using large-scale random regression test-day models.

Genetic parameters for milk, fat, and protein yield and persistency in the first 3 lactations of Polish Black and White cattle were estimated. A multiple-lactation model was applied with random herd-test-day effect, fixed regressions for herd-year and age-season of calving, and random regressions for the additive genetic and permanent environmental effects. Three data sets with slightly different edits on minimal number of days in milk and the size of herd-year class were used. Each subset included more than 0.5 million test-day records and more than 58,000 cows. Estimates of covariance components and genetic parameters for each trait were obtained by Bayesian methods using the Gibbs sampler. Due to the large size and a good structure of the data, no differences in estimates were found when additional criteria for record selection were applied. More than 95% of the genetic variance for all traits and lactations was explained by the first 2 principal components, which were associated with the mean yield and lactation persistency. Heritabilities of 305-d milk yield in the first 3 lactations (0.18, 0.16, 0.17) were lower than those for fat (0.12, 0.11, 0.12) and protein (0.13, 0.14, 0.15). Estimates of daily heritabilities increased in general with days in milk for all traits and lactations, with no apparent abnormalities at the beginning or end of lactation. Genetic correlations between yields in different lactations ranged from 0.74 (fat yield in lactations 1 and 3) to 0.89 (milk yield in lactations 2 and 3). Persistency of lactation was defined as the linear regression coefficient of the lactation curve. Heritability of persistency increased with lactation number for all traits and genetic correlations between persistency in different lactations were smaller than those for 305d yield. Persistency was not genetically correlated with the total yield in lactation.

Animals↗

Genetic parameters for within-litter variation in piglet birth weight and change in within-litter variation during suckling.

The objective of this study was to ascertain whether maternal additive genetic variance exists for within-litter variation in birth weight and for change in within-litter variation in piglet weight during suckling. A further objective was to estimate maternal genetic correlations of these two traits with mortality, birth weight, growth, and number of piglets born alive. Data were obtained from Lövsta research station, Swedish University of Agricultural Sciences, and included 22,521 piglets born in 2,003 litters by 1,074 Swedish Yorkshire sows. No cross fostering was used in the herd. The following seven traits were analysed in a multivariate animal (sow) model: number of piglets born alive, within-litter SD in birth weight, within-litter SD in piglet weight at 3 wk of age, mean weight at birth, mean weight at 3 wk of age, proportion of stillborn piglets, and proportion of dead piglets during suckling. Maternal genetic variance for the change in within-litter SD in piglet weight during suckling was assessed from the estimated additive genetic covariance components by conditioning on within-litter SD in birth weight. Similarly, mean growth of piglets during suckling was assessed from the additive genetic covariance components by conditioning on mean weight at birth. The heritability for within-litter SD in birth weight was 0.08 and 0.06 for within-litter SD in piglet weight at 3 wk. The genetic correlation between these two traits was 0.71. Little maternal genetic variance was found for the change in within-litter SD in piglet weight during suckling, and opportunity for genetic improvement of this trait by selective breeding seems limited. The genetic correlation of within-litter SD in birth weight with proportion of dead piglets during suckling was 0.25 and of within-litter SD in birth weight with mean growth of piglets was -0.31. The maternal genetic variance and heritability found for within-litter SD in birth weight indicates that genetic improvement of this trait by selective breeding is possible. In addition, selection for sows' capacity to give birth to homogeneous litters may be advantageous for piglet survival, piglet growth, and litter homogeneity at weaning.

Animals↗

Correlated responses in body composition to divergent selection for exponential growth rate to 14 or 42 days of age in chickens.

Chicks divergently selected for 14-d (14H and 14L) or 42-d (42H and 42L) exponential growth rate (EGR) over five generations were used to determine correlated responses between growth at different ages and body composition. Regression coefficient estimates across five generations of selection were not significant for any line at either age for percentage total body water or protein. Genetic correlations between EGR from hatching to 14 d of age (EGR14) and 42-d percentage carcass fat were -0.18, -0.57, 0.63, and -0.79 among the 14H, 14L, 42H, and 42L lines, respectively. Genetic correlations between EGR from hatching to 42 d of age (EGR42) and 42-d percentage carcass fat were 0.09, -0.67,0.50, and -0.75 among the 14H, 14L, 42H, and 42L lines, respectively. During the short-term selection experiment, selection for fast EGR14 or EGR42 increased fat at the age of selection. However, selection for fast EGR42 increased body weight and percentage fat at 42 d of age (DOA), whereas selection for fast EGR14 increased body weight but not fat at 42 DOA. Therefore, it is possible to simultaneously select for high body weight at, or near, the inflection point of the growth curve without increasing fat deposition or obesity by taking advantage of the lack of a genetic correlation between EGR14 and body fat percentage at later ages.

Aging↗

Evolution in heterogeneous environments: genetic variability within and across different grains in Tribolium castaneum.

The course of adaptation to heterogeneous environments is influenced by the magnitude of genetic variation for ecologically important characters within each environment and the extent of genotype x environment interaction. Using the genetic correlation between the expression of characters in different environments as a measure of genotype x environment interaction is particularly useful for evolutionary interpretation. In this study, we estimated patterns of genetic variability and cross-environment genetic correlations for pupal weight and development time in two strains of the flour beetle Tribolium castaneum in five flours (wheat with brewer's yeast, wheat, rice, corn and oat). Wheat plus yeast is the standard medium in which the strains have been reared for hundreds of generations; other flours are novel environments. The results indicated moderate levels of genetic variation within the various flours for pupal weight but not for development time. Performance varied considerably across flours, with the highest performance for both strains found in the standard medium and the poorest in oat flour. The genetic correlations of pupal weight across flours in both strains were generally not significantly different from + 1. This suggests that evolution of body size in different flours cannot proceed independently, and that improved performance in the novel flours may produce declines in fitness in the standard environment.

Animals↗

The relationship between vitamin D levels and depression: a genetically informed study.

BACKGROUND: Low vitamin D (vitD) levels are consistently associated with an increased risk of depression. However, the biological mechanisms underlying this relationship and potential shared genetic overlap remain elusive. METHODS: We investigated the genetic overlap and causal relationships between depression (N = 589,356) and vitD levels (N = 417,580) using genome-wide association study (GWAS) summary statistics. We performed genome-wide and local genetic correlation analyses, followed by quantification of polygenic overlap variants. Shared genetic loci were identified and mapped to genes, which were further analyzed through gene expression and lifespan brain expression trajectory analyses. Bidirectional causal relationships were examined using multiple Mendelian randomization approaches. RESULTS: We observed significant negative genetic correlations (rg = -0.079) and identified genetic overlap (N = 410 variants). Genes mapped to the 13 shared loci showed opposing expression patterns. Tissue- and cell-specific functional enrichment analyses revealed significant signals related to brain development, with distinct patterns emerging between fetal development and adulthood. Shared genes (TRMT61A, ITIH4, RASGRP1, CTNND1, HERC1, IP6K1, FURIN ESR1, ZMYND and GRM5) exhibited notable expression variation in the brian throughout the lifespan, aligning with functional enrichment findings. CONCLUSIONS: Our findings elucidate the shared biological mechanisms underlying the relationship between vitD and depression, suggesting that vitD play an important role in the development of depression through altered early neurodevelopmental processes.

Humans↗

Genotype x environment interactions in conventional versus pasture-based dairies in Canada.

The objective of this study was to evaluate effects of genotype x environmental interaction (GxE) on dairy traits among herds in Canada that practice intensive rotational grazing versus conventional methods that rely on stored feeds. Based on responses to questionnaires, 22 herds were selected for the grazing group and the conventional group consisted of 34 large free-stall dairies. Production data consisted of 6,749 lactations of 2,817 cows in the grazing herds and 29,371 lactations of 12,774 cows in the control herds. Subsets of data for reproduction and conformation also were created. Per cow production was greater in the conventionally managed herds (9,947 kg of milk) than in the grazing herds (9,400 kg). Phenotypic data were regressed on sire predicted transmitting abilities (PTA) and genetic correlations for all traits were estimated between environments. A scaling effect was observed across environments for yield traits, as phenotypic differences among cows were greater than predicted by sire PTA in conventional herds and consistent with sire PTA in grazing herds. Heritabilities for yield also were greater in conventional herds. Other effects of GxE were minor, with genetic correlations of near 0.90 or greater for all traits. Among yield traits, genetic correlation was lowest for fat (0.88 with SE = 0.04). These results demonstrate that effects of GxE are small between the two types of management systems analyzed and that graziers can accurately select sires based on national rankings.

Animal Feed↗

A genetic investigation of various growth models to describe growth of lambs of two contrasting breeds.

This study compared the use of various models to describe growth in lambs of 2 contrasting breeds from birth to slaughter. Live BW records (n = 7559) from 240 Texel and 231 Scottish Blackface (SBF) lambs weighed at 2-wk intervals were modeled. Biologically relevant variables were estimated for each lamb from modified versions of the logistic, Gompertz, Richards, and exponential models, and from linear regression. In both breeds, all nonlinear models fitted the data well, with an average coefficient of determination (R2) of > 0.98. The linear model had a lower average R2 than any of the nonlinear models (< 0.94). The variables used to describe the best 3 models (logistic, Gompertz, and Richards) included estimated final BW (A); maximum ADG (B); age at maximum ADG (C); position of point of inflection in relation to A (D, for Richards only). The Richards and Gompertz models provided the best fit (average R2 = 0.986 to 0.989) in both breeds. Richards estimated an extra variable, allowing increased flexibility in describing individual growth patterns, but the Akaike's information criteria value (which weighs log-likelihood by number of parameters estimated) was similar to that of the Gompertz model. Variables A, B, C, and D were moderately to highly heritable in Texel lambs (h2 = 0.33 to 0.87), and genetic correlations between variables within-model ranged from -0.80 to 0.89, suggesting some flexibility to change the shape of the growth curve when selecting for different variables. In SBF lambs, only variables from the logistic and Gompertz models had moderate heritabilities (0.17 to 0.56), but with high genetic correlations between variables within each model (< -0.88 or > 0.92). Selection on growth variables seems promising (in Texel more than SBF), but high genetic correlations between variables may restrict the possibilities to change the growth curve shape. A random regression model was also fitted to the data to allow predictions of growth rates at relevant time points. Heritabilities for growth rates differed markedly at various stages of growth and between the 2 breeds (Texel: 0.14 to 0.74; SBF: 0.07 to 0.34), with negative correlations between growth rate at 60 d of age and growth rate at finishing. Following these results, future studies should investigate genetic relationships between relevant growth curve variables and other important production traits, such as carcass composition and meat quality.

Age Factors↗

Estimates of genetic parameters for 320-day pelvic measurements of males and females and calving ease of 2-year-old females.

Records from 12 breed groups collected from 1983 to 1991, included in the Germ Plasm Utilization project at the U.S. Meat Animal Research Center, were analyzed separately by breed group and combined to estimate heritabilities and genetic correlations for 320-d male and female pelvic width, height, and area, and for 320-d male pelvic and female 2-yr-old calving ease. Calving ease was analyzed as a trait of the dam using 1) actual and 2) binary scale calving ease scores with a covariate of calf birth weight. A bivariate animal model and derivative-free REML incorporating sparse matrix techniques were used. When breed groups were analyzed separately, heritability estimates of male and female 320-d pelvic traits varied by breed group and sex. Average genetic correlations between male and female 320-d pelvic width, pelvic height, and pelvic area were large and positive. When breed groups were combined (n = 26,071), heritability estimates for 320-d pelvic traits were moderate in size. Genetic correlations of .68, .48, and .61, between male and female 320-d pelvic width, height, and area, respectively, suggest male and female pelvic traits are largely under the same genetic control but are correlated traits rather than the same trait. Heritability estimates for actual calving ease in 2-yr-olds ranged from .00 to .49 in separate breed group analyses, and from .00 to .37 for binary measures. When breed groups were combined, heritability was .11 for actual calving ease and was .09 on the binary scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Genetic aspects of control of anaemia development in trypanotolerant N'Dama cattle.

148 one-year-old N'Dama cattle, progeny of 29 sires, were exposed for 92 days to a medium natural tsetse-trypanosome challenge in Gabon, Central Africa. Matching health and performance data were recorded on 11 occasions. Average packed red cell volume percent (PCV) and lowest PCV reached during the period were evaluated as measures of ability to control the development of anaemia. Attempts were made to systematically control other possible causes of anaemia. In animals detected as parasitaemic, those with above average average PCV values or above average lowest PCV reached had 34% and 35% respectively higher daily weight gains than those with below average. Even when not detected as parasitaemic, those with above average average PCV values or above average lowest PCV reached had 14% and 12% respectively higher gain indicating that a proportion of these animals actually were parasitaemic. When all environmental and parasitaemia information was taken into account, the heritability of growth, average PCV and lowest PCV reached was 0.39 +/- 0.31, 0.64 +/- 0.33 and 0.50 +/- 0.32 respectively. The genetic correlation between average PCV and growth was 0.70 +/- 0.42 and between lowest PCV reached and growth was 0.28 +/- 0.55. While the standard errors are large, the higher heritabilities of PCV measures compared to animal growth and the positive genetic correlations between PCV and growth do indicate an opportunity for selection on PCV when animals can be detected as parasitaemic. All heritabilities and genetic correlations increased in size when parasitaemia information was utilized in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Genetic variance in nociception and its relationship to the potency of morphine-induced analgesia in thermal and chemical tests.

The perceived intensity of a painful stimulus is determined in part by the stimulus intensity and environmental conditions. The purpose of this study was to determine the influence of genetic factors in nociception and its contribution to the potency of morphine to produce antinociception. Eight inbred strains of mice were tested across a range of stimulus intensities in thermal (hot plate) and chemical irritant (acetic acid) nociceptive tests. Stimulus intensities in the thermal test included hot plate temperatures of 51, 53, 55, 57 and 59 degrees C. Stimulus intensities in the chemical irritant test included acetic acid concentrations of 0.1, 0.3 and 0.6%. Linear interpolation of stimulus-effect curves revealed large genotype-dependent differences in the effective temperature resulting in a 10 s latency on the hot-plate (ET10") and the acetic acid concentration resulting in the same number of writhes as determined by the area under the curve (AUC50). There was no genetic correlation between sensitivity to thermal versus chemical stimuli. Morphine dose response curves were then determined at a fixed stimulus intensity in each test (55 degrees C and 0.6% acetic acid) to determine analgesic ED50 doses for each inbred strain. A significant effect of genotype on relative sensitivity to morphine-induced analgesia in both the thermal and chemical irritant tests was found, however there was no genetic correlation between the potency of morphine in each test. There was an inverse genetic correlation between sensitivity to thermal and chemical stimuli and morphine ED50 values in each respective test. In both tests, strains less sensitive to the nociceptive stimuli were more sensitive to the antinociceptive effects of morphine. Confirmation studies in a separate genetic population confirmed the inverse relationship between hot-plate sensitivity and antinociceptive potency. In summary, this study demonstrated (i) a large degree of genetically-determined variability in sensitivity to painful stimuli, (ii) sensitivity to thermal stimuli (hot-plate) is genetically unrelated to sensitivity to chemical (acetic acid) stimuli, (iii) the mechanism by which morphine produces its antinociceptive effects against thermal stimuli is largely genetically independent of the mechanism by which morphine produces its antinociceptive effects against chemical stimuli, and (iv) inherent differences in sensitivity to painful stimuli may be responsible, in part, for individual differences in the potency of morphine's antinociceptive effects.

Acetic Acid↗