Noninbred Control Research Articles

Control of Protein and Energy Metabolism in the Pituitary Gland in Response to Three-Week Running Training in Adult Male Mice.

It is assumed that crosstalk of central and peripheral tissues plays a role in the adaptive response to physical activity and exercise. Here, we wanted to study the effects of training and genetic predisposition in a marathon mouse model on mRNA expression in the pituitary gland. Therefore, we used a mouse model developed by phenotype selection for superior running performance (DUhTP) and non-inbred control mice (DUC). Both mouse lines underwent treadmill training for three weeks or were kept in a sedentary condition. In all groups, total RNA was isolated from the pituitary gland and sequenced. Molecular pathway analysis was performed by ingenuity pathway analysis (IPA). Training induced differential expression of 637 genes (DEGs) in DUC but only 50 DEGs in DUhTP mice. Genetic selection for enhanced running performance strongly affected gene expression in the pituitary gland and identified 1732 DEGs in sedentary DUC versus DUhTP mice. Training appeared to have an even stronger effect on gene expression in both lines and comparatively revealed 3828 DEGs in the pituitary gland. From the list of DEGs in all experimental groups, candidate genes were extracted by comparison with published genomic regions with significant effects on training responses in mice. Bioinformatic modeling revealed induction and coordinated expression of the pathways for ribosome synthesis and oxidative phosphorylation in DUC mice. By contrast, DUhTP mice were resistant to the positive effects of three-week training on protein and energy metabolism in the pituitary gland.

Genome-wide regulatory deterioration impedes adaptive responses to stress in inbred populations of Drosophila melanogaster.

Inbreeding depression is often intensified under environmental stress (i.e., inbreeding-stress interaction). Although the fitness consequences of this phenomenon are well-described, underlying mechanisms such as an increased expression of deleterious alleles under stress, or a lower capacity for adaptive responses to stress with inbreeding, have rarely been investigated. We investigated a fitness component (egg-to-adult viability) and gene-expression patterns using RNA-seq analyses in noninbred control lines and in inbred lines of Drosophila melanogaster exposed to benign temperature or heat stress. We find little support for an increase in the cumulative expression of deleterious alleles under stress. Instead, inbred individuals had a reduced ability to induce an adaptive gene regulatory stress response compared to controls. The decrease in egg-to-adult viability due to stress was most pronounced in the lines with the largest deviation in the adaptive stress response (R2 = 0.48). Thus, we find strong evidence for a lower capacity of inbred individuals to respond by gene regulation to stress and that this is the main driver of inbreeding-stress interactions. In comparison, the altered gene expression due to inbreeding at benign temperature showed no correlation with fitness and was pronounced in genomic regions experiencing the highest increase in homozygosity.

Trait‐specific consequences of inbreeding on adaptive phenotypic plasticity

Environmental changes may stress organisms and stimulate an adaptive phenotypic response. Effects of inbreeding often interact with the environment and can decrease fitness of inbred individuals exposed to stress more so than that of outbred individuals. Such an interaction may stem from a reduced ability of inbred individuals to respond plastically to environmental stress; however, this hypothesis has rarely been tested. In this study, we mimicked the genetic constitution of natural inbred populations by rearing replicate Drosophila melanogaster populations for 25 generations at a reduced population size (10 individuals). The replicate inbred populations, as well as control populations reared at a population size of 500, were exposed to a benign developmental temperature and two developmental temperatures at the lower and upper margins of their viable range. Flies developed at the three temperatures were assessed for traits known to vary across temperatures, namely abdominal pigmentation, wing size, and wing shape. We found no significant difference in phenotypic plasticity in pigmentation or in wing size between inbred and control populations, but a significantly higher plasticity in wing shape across temperatures in inbred compared to control populations. Given that the norms of reaction for the noninbred control populations are adaptive, we conclude that a reduced ability to induce an adaptive phenotypic response to temperature changes is not a general consequence of inbreeding and thus not a general explanation of inbreeding–environment interaction effects on fitness components.

The effects of inbreeding and heat stress on male sterility inDrosophila melanogaster

Understanding the consequences of inbreeding in combination with stress is important for the persistence of small endangered populations in a changing environment. Inbreeding and stress can influence the population at all stages of the life cycle, and in the last two decades a number of studies have demonstrated inbreeding depression for most life-cycle components, both in laboratory populations and in the wild. Although male fertility is known to be sensitive to temperature extremes, few studies have focused on this life-cycle component. We studied the effects of inbreeding on male sterility in benign and stressful environments using Drosophila melanogaster as a model organism. Male sterility was compared in 21 inbred lines and five non-inbred control lines at 25.0 and 29.0 degrees C. The effect of inbreeding on sterility was significant only at 29.0 C. This stress-induced increase in sterility indicates an interaction between the effects of inbreeding and high-temperature stress on male sterility. In addition, the stress-induced temporary and permanent sterility showed significant positive correlation, as did stress-induced sterility and the decrease in egg-to-adult viability. This suggests that the observed stress-induced decline in fitness could result from conditionally expressed, recessive deleterious alleles affecting both sterility and viability simultaneously. (C) 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104, 432-442.

Slow inbred lines of Drosophila melanogaster express as much inbreeding depression as fast inbred lines under semi-natural conditions

Selection may reduce the deleterious consequences of inbreeding. This may be due to purging of recessive deleterious alleles or balancing selection favouring heterozygote offspring. Such selection is expected to be more efficient at slower compared to at faster rates of inbreeding. In this study we tested the impact of inbreeding and the rate of inbreeding on fitness related traits (egg productivity, egg-to-adult viability, developmental time and behaviour) under cold and benign semi-natural thermal conditions using Drosophila melanogaster as a model organism. We used non-inbred control and slow and fast inbred lines (both with an expected inbreeding level of 0.25). The results show that contrary to expectations the slow inbred lines do not maintain higher average fitness than the fast inbred lines. Furthermore, we found that stressful environmental conditions increased the level of inbreeding depression but the impact of inbreeding rate on the level of inbreeding depression was not affected by the environmental conditions. The results do not support the hypothesis that inbreeding depression is less severe with slow compared to fast rates of inbreeding and illustrate that although selection may be more efficient with slower rates of inbreeding this does not necessary lead to less inbreeding depression.

Trait specific consequences of fast and slow inbreeding: lessons from captive populations of Drosophila melanogaster

The increased homozygosity due to inbreeding leads to expression of deleterious recessive alleles, which may cause inbreeding depression in small populations. The severity of inbreeding depression has been suggested to depend on the rate of inbreeding, with slower inbreeding being more effective in purging deleterious alleles of smaller effect. The effectiveness of purging is however dependent on various factors such as the effect of the deleterious, recessive alleles, the genetic background of inbreeding depression and the environment in which purging occurs. Investigations have shown inconclusive results as to whether purging efficiently diminish inbreeding depression. Here we used an ecologically relevant inbreeding coefficient (f ≈ 0.25) and generated ten slow and ten fast inbred lines of Drosophila melanogaster by keeping the effective population size constant at respectively 32 and 2 for 19 or 2 generations. These inbred lines were contrasted to non-inbred control lines. We investigated the effect of inbreeding and inbreeding rate in traits associated with fitness including heat, cold and desiccation stress resistance, egg-to-adult viability, development time, productivity, metabolic rate and wet weight under laboratory conditions. The results showed highly trait specific consequences of inbreeding and generally no support for the hypothesis that slow inbreeding is less deleterious than fast inbreeding. Egg-to-adult viability and development time were investigated under both benign and heat stress conditions. Reduced viability and increased developmental time were observed at stressful temperatures and inbreeding depression was on average more severe at stressful compared to benign temperatures.

Efficiency of selection, as measured by single nucleotide polymorphism variation, is dependent on inbreeding rate in Drosophila melanogaster

It is often hypothesized that slow inbreeding causes less inbreeding depression than fast inbreeding at the same absolute level of inbreeding. Possible explanations for this phenomenon include the more efficient purging of deleterious alleles and more efficient selection for heterozygote individuals during slow, when compared with fast, inbreeding. We studied the impact of inbreeding rate on the loss of heterozygosity and on morphological traits in Drosophila melanogaster. We analysed five noninbred control lines, 10 fast inbred lines and 10 slow inbred lines; the inbred lines all had an expected inbreeding coefficient of approximately 0.25. Forty single nucleotide polymorphisms in DNA coding regions were genotyped, and we measured the size and shape of wings and counted the number of sternopleural bristles on the genotyped individuals. We found a significantly higher level of genetic variation in the slow inbred lines than in the fast inbred lines. This higher genetic variation was resulting from a large contribution from a few loci and a smaller effect from several loci. We attributed the increased heterozygosity in the slow inbred lines to the favouring of heterozygous individuals over homozygous individuals by natural selection, either by associative over-dominance or balancing selection, or a combination of both. Furthermore, we found a significant polynomial correlation between genetic variance and wing size and shape in the fast inbred lines. This was caused by a greater number of homozygous individuals among the fast inbred lines with small, narrow wings, which indicated inbreeding depression. Our results demonstrated that the same amount of inbreeding can have different effects on genetic variance depending on the inbreeding rate, with slow inbreeding leading to higher genetic variance than fast inbreeding. These results increase our understanding of the genetic basis of the common observation that slow inbred lines express less inbreeding depression than fast inbred lines. In addition, this has more general implications for the importance of selection in maintaining genetic variation.

Effects of a single event of close inbreeding on growth and survival in steelhead

For two populations of Alaskan steelhead (Oncorhynchus mykiss) of common ancestry we evaluated effects of inbreeding in second-generation descendants of wild fish by comparing progeny of full-sibling matings to those of non-inbred controls to determine if a single event of close inbreeding has significant effects on survival and growth in captivity or the wild. In captivity, both survival and size were highly variable between inbred and control types within each line and among the five broods during five periods of freshwater culture. However, no consistent patterns of inbreeding enhancement or depression between types within lines across years were evident. In contrast, in the wild marine environment, 34 of 34 pairwise comparisons between inbred and control types in body size of returning adults after 2 or 3 years at liberty in the ocean were consistent with inbreeding depression with significant inbreeding depression varying from 2.9% for female length to 20.0% for female weight. Survival of marked juveniles (smolts) to adults in the wild marine environment was consistently and significantly lower in inbred types for both lines, for an average inbreeding depression of 78.8%. The results underscore the potential problems that can arise from using protective culture technologies, including captive broodstocks, to supplement endangered populations, and they highlight the genetic hazards that can be faced by small wild populations. This study demonstrates that high natural mortality or selection increases the amount of inbreeding depression detected in survival. Inbreeding effects on survival and growth in captivity can be poor indicators of survival and growth in a wild marine environment.

Trait mean depression for second-generation inbred strawberry populations with and without parent selection

Strawberry genotypes selected for superior fruit yield or chosen at random from first-generation self, full-sib, and half-sib populations were crossed to provide second-generation inbred progenies and composite cross-fertilized control populations. Mean yields for inbred offspring from crosses among selected parents exceeded those from the offspring of unselected parents by 87%, 23%, and 37% for self, full-sib, and half-sib populations, respectively; yields for offspring from unrelated crosses among selected parents were 54% larger than those for crosses among unselected parents. Selection for yield also resulted in significant correlated response for fruit number and plant diameter. Mean yields for second-generation half-sib and full-sib offspring from selected parents were greater than those for offspring from the unselected but non-inbred control population. This suggests that selection can be a powerful force in counteracting most of the inbreeding depression expected in cross-fertilized strawberry breeding programs. Selection treatment× inbreeding rate interactions were non-significant for all traits; thus, selection among partially inbred offspring did not have a large effect on the rate of genetic progress. Differential realized selection intensity among individuals with differing levels of homozygosity accumulated due to inbreeding is suggested as the most likely explanation for the absence of association between pedigree inbreeding coefficients and cross performance detected previously in strawberry.

Ten-year linear trends in reproduction and wool production among inbred and noninbred lines of Rambouillet, Targhee, and Columbia sheep1

To investigate the value of creating inbred lines for genetic improvement of sheep, 54 inbred, 1 randombred control, and 3 noninbred control lines were evaluated for lamb and wool production. Results were based on 19,438 dam and 23,625 lamb records from Rambouillet (R), Targhee (T), and Columbia (C) sheep collected over 9 yr (for T and C) and 10 yr (for R), starting in 1954. Average inbreeding in the inbred lines during the period was near 25% for lambs and 20% for ewes. The general trend in inbred lines for litter weight weaned (120 d) and number weaned (net reproductive rate), per ewe exposed to breeding, was downward as inbreeding increased. Trends in fleece weight generally also were down, regardless of concomitant increases in body weight. Declines were most pronounced in two lines developed by rapid inbreeding. Reproductive merit in the R and C noninbred controls also declined, but the declines were less than those for most inbred lines. Although the T noninbred control declined in fleece weight, trends for fleece weight in the R and C controls were positive and significantly different from the negative trends in the inbred lines. For the randombred control, slight downward trends in litter weight and number weaned were less (P < .05) than those for most inbred lines, indicating genetic declines in these traits for most inbred lines. Direct selection for an index of overall phenotypic merit, recurrent selection for combining ability for overall merit, and direct selection for body type, clean fleece weight, or staple length were all ineffective in preventing a decline in reproductive merit. Ending means (last 2 yr of production) revealed that litter weight weaned in the control groups of each breed was clearly superior to that in most inbred lines. Controls also were typically superior for fleece and body weight. Not one of the 54 inbred lines was superior (P < .05) to its respective noninbred control in weight of lamb weaned or net reproductive rate. Only four of the inbred lines were superior to the noninbred controls in fleece weight. These results, after at least 23 yr of development for most lines, reflect little encouragement for the costly development of many inbred lines for the purpose of improving lamb and wool production, especially when using the above selection criteria.

Response of genetic hypercalciuric rats to a low calcium diet

A fundamental mechanism for hypercalciuria in genetic hypercalciuric rats appears due to a primary increase in intestinal calcium absorption. However previous studies could not exclude additional mechanisms to account for the hypercalciuria. To determine if enhanced bone mineral dissolution either as a primary abnormality or secondary to a defect in renal tubule calcium reabsorption is responsible for a component of the augmented calcium excretion we studied rats continually inbred for hypercalciuria. Nineteenth generation adult female idiopathic hypercalciuric (IH) and non-inbred control (Ctl) rats were fed 13 g/day of a normal calcium diet (0.6% calcium, NCD) for 10 days. Urine calcium excretion over the last seven days was greater in IH (34 +/- 2 mg/7 day) than in Ctl (2.9 +/- 0.3, P < 0.01) rats. Some rats in each group were continued on the same diet while others were fed a low calcium diet (0.02% calcium, LCD) for an additional 10 days; balance measurements were made over the final seven days. With LCD, urine calcium excretion was approximately 8-fold higher in IH compared to Ctl (13 +/- 2 mg/7 day vs. 1.6 +/- 0.1, IH vs. Ctl, respectively, P < 0.01). In IH rats percent calcium absorption was greater (59 +/- 3% vs. 45 +/- 3, IH vs. Ctl, P < 0.01), however calcium retention was negative (-1.9 +/- 2.0 mg/7 day vs. 6.5 +/- 0.5, IH vs. Ctl, P < 0.01) compared to Ctl rats. The fall in urine calcium excretion when IH rats are fed LCD indicates that enhanced intestinal calcium absorption is a primary mechanism of the hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Inbreeding and Diseases: Demographic, Genetic, and Epidemiologic Perspectives

The demographic and quantitative genetic aspects of consanguineous marriages are reviewed before epidemiologic principles are applied to the hundreds of studies reviewed, and 3 in particular. Consanguineous unions range from cousin-cousin to more distant relatedness, and their prevalence varies by culture. Prevalence is highest in Arab countries, followed by India, Japan, Brazil and Israel. They are most common in lower educational and socioeconomic groups, the traditionally religious, and the early married, but are declining with modernization. Consanguinity is measured by geneticists by the inbreeding coefficient, the mean consanguinity of a population, and the concept of genetic load. Recessive genes may be deleterious or beneficial if heterozygous in local conditions. Bayesian statistics can predict by the coefficient of increase the probability of disease in offspring as a function of consanguinity and disease characteristics. Inbreeding generally increases prereproductive mortality; crude mortality increases with inbreeding in proportion to the mortality rate. Morbidity increases significantly with inbreeding in many diseases studies in many countries. Epidemiologic studies usually measure inbreeding effects in terms of genetic load, which is not readily translatable into morbidity and mortality. Several methods of computing results of epidemiologic studies are discussed, as well as methodological study design problems. Confounding is the most difficult problem in these studies, because of the difficulty in selecting non-inbred controls. Future inbreeding studies should be interpreted based on both genetic and epidemiologic grounds to illuminate the role of genetic factors and the relevance of inbreeding to disease and public health.

Weaning trait comparisons among inbred lines and selected noninbred and randomly bred control groups of Rambouillet, Targhee and Columbia sheep.

A program of inbreeding with concurrent selection was followed in the development of 26 Rambouiller, 20 Targhee and 10 Columbia inbred lines for subsequent linecross and topcross performance evaluation. Inbreeding coefficients averaged 30.4, 28.5 and 29.8% for the three breeds, respectively, at the end of the study. Selected noninbred control and unselected randomly bred control groups were maintained for each breed. Weaning trait data were evaluated for 1,332 Rambouillet, 1,557 Targhee and 1,049 Columbia inbred line and control group lambs during the final 2 years of inbreeding. Results showed a slight response to selection within inbred lines for the more highly heritable traits and some degree of genetic divergence among lines at the current levels of inbreeding. In general, the traits most sensitive to inbreeding depression were those more closely associated with fitness and those of low to moderate heritability. Even though a fairly large number of lines was developed, only a few inbred lines were superior (P less than .05) to their respective selected control groups - and usually for only one trait. Significantly, not a single Rambouillet, Targhee or Columbia inbred line was superior (P less than .05) in overall merit to its appropriate selected control group. Unselected control group means tended to be slightly superior to means for most inbred lines for traits of low heritability (weaning weight, body type and body condition) and inferior for more highly heritable traits (staple length, face cover, and neck folds). Notably, only six of a total of 56 inbred lines were superior (P less than .05) in overall merit to their appropriate unselected control groups.

The allograft reaction as an index of genetic diversity in inbred chickens

The main purpose of the study was to use the skin allograft reaction as a possible biological tool to estimate genetic diversity (inbreeding) in a population and to determine the relative influence on the B locus blood group locus on variation in graft rejection. In chickens, the B locus is the major histocompatibility system. One outbred and five inbred lines were used in 12 skin grafting experiments. Graft exchange also were made between certain line crosses. The study was based on 2172 allografts performed on 712 chickens.Incompatibility of the B blood group locus accounted for 3/4 of the total variance in homograft rejection within lines. For the compatible allografts only, lines accounted for more than 90% of the total variation.Graft acceptance in terms of mean survival time (MST) was highest in the most highly inbred lines and lowest in the noninbred control. The regression of genetic diversity, as a function Wright's inbreeding coefficient, as a percentage of allograft rejection may be a useful biological index of genetic diversity.

Abnormal Body Curvatures of Rainbow Trout (Salmo gairdneri) Inbred Fry

In an inbreeding experiment with rainbow trout (Salmo gairdneri), a special type of deformed fry was found. The deformity appeared after one generation of fullsib mating in one of nine fullsib groups. The deformed fry were observed soon after the resorption of the yolk sac and showed different forms of body curvatures. The deformity was lethal. Significant differences between inbred groups and the noninbred control groups indicate that the deformity is at least partly heritable.

Alterations in norepinephrine storage in inbred rats made hypertensive by triiodothyronine and sodium chloride.

The endogenous catecholamine content, norepinephrine retention, and the activity of enzymes involved in the synthesis and degradation of catecholamines were examined in several organs of inbred rats which developed hypertension as a result of triiodothyronine and NaCl administration. In hypertensive inbred rats given triiodothyronine and NaCl there was a decrease in content and retention of H³-nor-epinephrine. The decreased retention of H³-nor-epinephrine in hypertensive rats reflects increased turnover of the amine. Normotensive inbred rats not given triiodothyronine and NaCl had an increased norepinephrine content in the heart when compared to non-inbred control rats. Cardiac monoamine oxidase activity was increased, but catechol-O-methyl transferase unaltered in the hypertensive rats. The norepinephrine content in the gut and submaxillary gland was increased as a result of inbreeding, but the development of hypertension decreased the content to the range of noninbred control tissues. An increased retention of H³-norepinephrine was found in the gut and submaxillary gland as a result of inbreeding alone, and this was not altered by the presence of hypertension. Adrenal tyrosine hydroxylase activity, phenylethanolamine-N-methyl transferase activity and epinephrine were slightly elevated in the inbred hypertensive group, but no change in sympathetic ganglia tyrosine hydroxylase activity was demonstrated. Thus it appears that the hypertensive state produced by triiodothyronine and NaCl is accompanied by changes in catecholamine storage and synthetic enzymes whick in general resemble those previously reported for DOCA-NaCl hypertensive rats.

Inbreeding depression and heterosis of litter size in mice

1. A random bred population of mice was subjected to inbreeding and the changes of litter size, measured as the number of live young in first litters, were followed.2. The mean litter size declined at a rate of 0·56 young per 10% increase of the inbreeding coefficient.3. Selection for large litters within the lines during the inbreeding did not effectively reduce the rate of decline.4. Out of twenty lines at the beginning of the inbreeding seventeen were lost by the time the inbreeding coefficient reached 76%. Two more were lost later and one survived indefinitely. The three lines that survived longest started at a level below the mean and did not decline in litter size. The one that survived indefinitely reached 99% inbreeding without dropping below the non-inbred control.5. The three lines surviving at 81% inbreeding were crossed and the litters produced by the crossbred progeny were larger than the non-inbred control by about two young per litter. This gain from heterosis is attributable to selection among the lines on their performance as inbreds. A second and third cycle of inbreeding and crossing yielded no further progress, and the level of the first cross was never regained. This is attributable to the ineffectiveness of the selection applied and to the previous restrictions of the population size.6. The behaviour of the lines in the inbreeding and crossing point to simple dominance rather than over-dominance at the loci causing variation of litter size.7. This experiment suggests that, as a means of improvement of farm animals, cyclical inbreeding and crossing does not look very hopeful.