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PubMed1985

Effectiveness of genetic selection for prolificacy in pigs.

This paper attempts to summarize and discuss the new evidence on the effectiveness of selection for prolificacy. In recent years selection between lines, and the adoption of formal cross-breeding programmes, have led to considerable improvements at a commercial level. Within-line selection has not been tackled seriously except in a few experiments. The mainly negative results from these should not lead to the conclusion that progress is impossible, but rather that it needs larger resources, applied consistently for several generations, to overcome the inherent problems. There are now many estimates of genetic parameters, based on large data sets, and these have helped to clear up some of the confusion resulting from previous inadequate material. A heritability of around 0.1, repeatability of 0.15, and fairly high genetic correlations between successive records seem justified. The negative environmental effect of being reared in a large litter is frequently present, but there is no good reason why this should seriously affect attempts to improve the trait by selection. Information from a candidate's relatives other than its dam can undoubtedly increase the accuracy with which its breeding value is estimated, but the routine use of such data in practical programmes is not straightforward. Prolificacy is only one group of traits contributing to net economic worth. The need to strike a balance between all relevant traits is explored in the particular context of a scheme based on hyperprolific sows. Finally, selection can only have lasting and cumulative effectiveness if it is applied at the top of a pyramid of improvement. Both culling and selection of replacement gilts within the commercial sector are largely irrelevant.

Animals↗
PubMed2000

Differential susceptibility to periodontitis in genetically selected Wistar rat lines that differ in their behavioral and endocrinological response to stressors.

This study tests the model presented previously by Breivik et al. (1996), in which the extent of periodontitis, an inflammatory disease, is predicted from the reactivity of the HPA-axis. Briefly, the model implies that elevated plasma levels of corticosterone modulate the immune system by shifting the T-helper balance toward a more Th2 response, which, alternately, increases the sensitivity to periodontitis. To test this model, two genetically distinct types of rats that differ both behaviorally and endocrinologically in their response to stress (high corticosterone responding APO-SUS rats and low corticosterone responding APO-UNSUS rats) were compared. Periodontitis was experimentally induced through the placement of a ligature and measured as the extent of tissue (fiber and bone) loss, both histologically and radiographically. The results show that, as expected, APO-SUS animals are more sensitive to periodontitis, i.e., show more fiber and bone loss, than APO-UNSUS animals. These data are in agreement with findings in Fischer and Lewis rats, as well as with corticosterone treated and adrenalectomized animals and suggest that genetic factors underlying the variation in the reactivity of the HPA-axis (and, accordingly, their behavioral response to stress) play an important a role in the development of inflammatory diseases.

Animals↗
PubMed1993

Genetic selection for crescent formation yields mouse strain with rapidly progressive glomerulonephritis and small vessel vasculitis.

We have established a recombinant inbred strain of mouse named spontaneous crescentic glomerulonephritis-forming mouse/Kinjoh or SCG/Kj. Mice of this strain spontaneously develop rapidly progressive glomerulonephritis. This strain of mice was derived from (BXSB/Mp x MRL/Mp-lpr/lpr)F1 hybrid mice by brother x sister mating coupled with repeated histopathologic selection for breeding of mice whose parents had the highest frequency of crescent formation in the kidneys. In this strain of mice, nephritis appears earlier and is more rapidly progressive than in any other murine model of systemic lupus erythematosus. Histopathologically, the characteristic renal lesions in the mice of this strain express a most dramatic form of crescentic glomerulonephritis. The lesions in the kidneys show only slight fine granular immune deposits along the glomerular basement membrane associated with remarkable extraglomerular proliferation and hemorrhage in Bowman's space. Although selection was not based on vasculitis, mice of this strain also exhibit a high incidence of necrotizing vasculitis. These vascular lesions involve primarily small arteries and arterioles and many organs and tissues but spare the kidneys. Thus this form of vasculitis has been found to be correlated with the crescentic form of glomerulonephritis but not with lymphoid hyperplasia of the spleen. We conclude that, in this strain of mouse, the rapidly progressive glomerulonephritis is genetically restricted and that this genetic restriction is firmly linked to that responsible for the vasculitis.

Animals↗
PubMed1993

Identification of Aspergillus brlA response elements (BREs) by genetic selection in yeast.

The brlA gene of Aspergillus nidulans plays a central role in controlling conidiophore development. To test the hypothesis that brlA encodes a transcriptional regulator and to identify sites of interaction for the BrlA polypeptide, we expressed brlA in Saccharomyces cerevisiae (yeast) strains containing Aspergillus DNA sequences inserted upstream of a minimal yeast promoter fused to the Escherichia coli lacZ gene. Initially, a DNA fragment from the promoter region of the developmentally regulated rodA gene was tested and shown to mediate brlA-dependent transcriptional activation. Two additional DNA fragments were selected from an Aspergillus genomic library by their ability to respond to brlA in yeast. These fragments contained multiple copies of a sequence motif present in the rodA fragment, which we propose to be sites for BrlA interaction and designate brlA response elements (BREs). DNA fragments containing BREs upstream of a minimal Aspergillus promoter were capable of conferring developmental regulation in Aspergillus. Deletion of BREs from the upstream region of rodA greatly decreased its developmental induction. Multiple copies of a synthetic oligonucleotide with the consensus sequence identified among the BREs mediated brlA-dependent transcriptional activation in yeast. The results show that a primary activity of brlA is transcriptional activation and tentatively identify sites of interaction for the BrlA polypeptide.

Aspergillus nidulans↗
PubMed2005

Sexual selection, genetic architecture, and the condition dependence of body shape in the sexually dimorphic fly Prochyliza xanthostoma (Piophilidae).

The hypothesis that sexual selection drives the evolution of condition dependence is not firmly supported by empirical evidence, and the process remains poorly understood. First, even though sexual competition typically involves multiple traits, studies usually compare a single sexual trait with a single "control" trait, ignoring variation among sexual traits and raising the possibility of sampling bias. Second, few studies have addressed the genetic basis of condition dependence. Third, even though condition dependence is thought to result from a form of sex-specific epistasis, the evolution of condition dependence has never been considered in relation to intralocus sexual conflict. We argue that condition dependence may weaken intersexual genetic correlations and facilitate the evolution of sexual dimorphism. To address these questions, we manipulated an environmental factor affecting condition (larval diet) and examined its effects on four sexual and four nonsexual traits in Prochyliza xanthostoma adults. As predicted by theory, the strength of condition dependence increased with degree of exaggeration among male traits. Body shape was more condition dependent in males than in females and, perhaps as a result, genetic and environmental effects on body shape were congruent in males, but not in females. However, of the four male sexual traits, only head length was significantly larger in high-condition males after controlling for body size. Strong condition dependence was associated with reduced intersexual genetic correlation. However, homologous male and female traits exhibited correlated responses to condition, suggesting an intersexual genetic correlation for condition dependence itself. Our findings support the role of sexual selection in the evolution of condition dependence, but reveal considerable variation in condition dependence among sexual traits. It is not clear whether the evolution of condition dependence has mitigated or exacerbated intralocus sexual conflict in this species.

Animals↗
PubMed1995

Analysis of RNA-binding proteins by in vitro genetic selection: identification of an amino acid residue important for locking U1A onto its RNA target.

An in vitro genetic system was developed as a rapid means for studying the specificity determinants of RNA-binding proteins. This system was used to investigate the origin of the RNA-binding specificity of the mammalian spliceosomal protein U1A. The U1A domain responsible for binding to U1 small nuclear RNA was locally mutagenized and displayed as a combinatorial library on filamentous bacteriophage. Affinity selection identified four U1A residues in the mutagenized region that are important for specific binding to U1 hairpin II. One of these residues (Leu-49) disproportionately affects the rates of binding and release and appears to play a critical role in locking the protein onto the RNA. Interestingly, a protein variant that binds more tightly than U1A emerged during the selection, showing that the affinity of U1A for U1 RNA has not been optimized during evolution.

Amino Acid Sequence↗
PubMed1986

Genetic selection of a Plasmodium-refractory strain of the malaria vector Anopheles gambiae.

The anopheline mosquito is the target in most malaria control programs, primarily through the use of residual insecticides. A mosquito was studied that is refractory to most species of malaria through a genetically controlled mechanism. A strain of Anopheles gambiae, which was selected for complete refractoriness to the simian malaria parasite Plasmodium cynomolgi, also has varying degrees of refractoriness to most other malaria species examined, including the human parasites P. falciparum, P. ovale, and P. vivax for which this mosquito is the principal African vector. Furthermore, the refractoriness extends to other subhuman primate malarias, to rodent malaria, and to avian malaria. Refractoriness is manifested by encapsulation of the malaria ookinete after it completes its passage through the mosquito midgut, approximately 16 to 24 hours after ingestion of an infective blood meal. Fully encapsulated ookinetes show no abnormalities in parasite organelles, suggesting that refractoriness is due to an enhanced ability of the host to recognize the living parasite rather than to a passive encapsulation of a dead or dying parasite. Production of fully refractory and fully susceptible mosquito strains was achieved through a short series of selective breeding steps. This result indicates a relatively simple genetic basis for refractoriness. In addition to the value these strains may serve in general studies of insect immune mechanisms, this finding encourages consideration of genetic manipulation of natural vector populations as a malaria control strategy.

Animals↗
PubMed2002

Differences in composition of avian bone collagen following genetic selection for resistance to osteoporosis.

1. Collagen characteristics were compared in the tibiotarsus and humerus from 103 females and 38 males aged 68 to 72 weeks from the G6 generation of lines of laying hen selected for resistance or susceptibility to osteoporosis (high and low bone index (BI) lines). 2. Selection over the latest generation resulted in further divergence in the breaking strengths of humerus (from 12.3 to 21.8%) and tibia (from 22.3 to 37.3%) in hens. Males also showed line differences in bone strengths. 3. Plasma pyridinoline concentration was higher in hens in the low BI line, suggesting a greater rate of bone resorption in this line. 4. There were few differences between the lines in collagen and calcium concentrations in humerus and tibiotarsus cortical bone. 5. There were no differences between the lines in either sex in reduced immature collagen cross-link content of humerus or tibiotarsus. 6. Mature collagen cross-link content was higher in the high BI line in the male humerus but this effect was not apparent in the male tibiotarsus nor in either bone in the females. 7. Pyrrolic cross-link contents were higher in the high BI line in the female humerus and tibiotarsus and in the male tibiotarsus. 8. Over both lines combined, there were positive correlations between humeral and tibiotarsal pyrrole contents and strengths in females and between tibiotarsal pyrrole content and strength in males. 9. It is concluded that an increase in cross-linking, particularly pyrrolic cross-linking, in the collagen matrix contributes in part to the improvement in bone strength in the high BI line.

Amino Acids↗
PubMed1989

Genetic selection and DNA sequences of 4.5S RNA homologs.

A general strategy for cloning the functional homologs of an Escherichia coli gene was used to clone homologs of 4.5S RNA from other bacteria. The genes encoding these homologs were selected by their ability to complement a deletion of the gene for 4.5S RNA. DNA sequences of the regions encoding the homologs were determined. Since this approach does not require that the homologous genes hybridize with probes generated from the E. coli sequence, the sequences of the homologs were not all similar to the sequence of the E. coli gene. Despite the dissimilarity of the primary sequences of some of the homologs, all could be folded to obtain a similar structure.

Bacillus subtilis↗
PubMed1993

Divergent genetic selection for incidence of tibial dyschondroplasia in broilers at seven weeks of age.

Selection for a high (H) or low (L) incidence of tibial dyschondroplasia (TD) at 7 wk of age was practiced for four generations in broiler breeders using low intensity x-ray imaging (Lixiscope) for TD diagnosis. As a result, broiler lines with H or L incidence of TD at 7 wk of age were developed keeping a randomly selected control (C) broiler line. A total of 4,232 chicks were hatched representing 172 sires and 612 dams over four generations for the H, L, and C lines. The TD scores at 7 wk were collected on 4,056 broilers. Incidence of TD at 4 and 7 wk of age were studied in the C, H, and L lines of broilers. Direct response to selection in the H and L lines were estimated per generation and per weighted cumulative selection differential (WCSD). Total WCSD deviation from the C line for incidence of TD at 7 wk of age was 1.496 and -.42 units for the H and the L lines, respectively. The response per generation for incidence of TD at 7 wk of age for the H line was .153 +/- .028 units. The realized heritability for the H line for incidence of TD at 7 wk of age was .437 +/- .065. The incidence of TD was not significantly decreased in the L line at 7 wk of age.

Analysis of Variance↗
PubMedDate not supplied

Genetic selection for high acute inflammatory response confers resistance to lung carcinogenesis in the mouse.

Mice selected for a high acute inflammatory response (AIRmax) are resistant to chemically induced lung tumorigenesis, whereas the low responders (AIRmin) are susceptible. In urethane-treated mice, anti-inflammatory drugs increased the tumor incidence in AIRmax but not AIRmin mice, and an inverse correlation (P<.001) between the degree of acute inflammatory response (AIR) and lung tumorigenesis was found in an F2 (AIRmax x AIRmin) intercross population. The results provide evidence for the involvement of lung tumor modifier loci in AIR regulation and implicate AIR quantitative trait loci in the inherited predisposition to lung cancer.

Acute Disease↗
PubMedDate not supplied

Effects of genetic selection for high or low antibody response on resistance to a variety of disease challenges and the relationship of resource allocation.

Lines of white leghorn chickens were selectively bred for either a high (H) or low (L) antibody response to sheep erythrocytes. The parental lines, HH and LL, and reciprocal crosses, HL (sire line cited first and dam line second) and LH, were compared for their responses to various diseases. High antibody titers were associated with reduced body weight. Lines and their crosses were challenged with infectious diseases. The LL line was most resistant to Mycobacterium avium, whereas the HH line was most susceptible. The HH line was most resistant to Mycoplasma gallisepticum, whereas the LL line was most susceptible. These findings indicate that defense against infectious diseases are resource expensive. In order to save resources, it is possible that different parts of a population might genetically devote high levels of resources against different types of diseases so that the entire population is not susceptible to a single infection.

Animals↗
PubMed2006

Inflammatory lesion and parasite load are inversely associated in Leishmania amazonensis infected mice genetically selected according to oral tolerance susceptibility.

Two strains of mice selected according to extreme phenotypes of susceptibility and resistance to oral tolerance (TS and TR mice, respectively) were infected with 1 x 10(7) Leishmania amazonensis promastigotes and studied comparatively. TS mice developed a minor pathology while permitting parasite growth with the presence of increased IL-4, IL-10 and IFN-gamma, and lower NO and IL-2 levels and delayed-type hypersensitivity (DTH). In contrast, in TR mice, footpad swelling was increased but parasite growth was reduced. They produced lower IL-4, IL-10 and IFN-gamma but increased NO, IL-2 levels, DTH, activated spleen macrophages and periarteriolar lymphoid sheaths. The results suggest that the tolerogenic TS mouse profile, with higher IL-10 production, impaired lesion development but also avoided macrophage leishmanicidal activity, maintaining in this manner a silent parasite load. On the other hand, the TR mouse profile contributed to lesion progression with controlled parasite load. To directly address the influence of oral tolerance on infection, mice were gavaged with OVA, and 7 days afterwards were infected and challenged to bystander suppression with OVA in the same footpad. In TR mice gavaged with 25 mg OVA the inflammatory lesion was largely enhanced, while with 5 mg OVA the lesion was diminished. In TS mice the footpad swelling was always lower. However, the bystander effect did not modify the establishment of infection; and similarly to the control non-bystander mice, parasite clearance was maintained in TR and prevented in TS mice. Therefore, a better comprehension of immunoregulation of innate and adaptive immunity in the early stages of infection is necessary for the development of protocols preventing inflammation and contributing to the elimination of parasites.

Administration, Oral↗
PubMed2000

Effects of repeated restraint in Japanese quail genetically selected for contrasting adrenocortical responses.

Behavioral and adrenocortical responses to repeated mechanical restraint were compared in 28-day-old to 31-day-old male Japanese quail from two genetic lines divergently selected for reduced (low stress, LS) or exaggerated (high stress, HS) plasma corticosterone (C) responses to brief immobilization. Restraint in a metal crush cage for 5 min elicited immobility and silence in all the birds. Circulating C levels were considerably higher in quail of both lines following restraint than in the undisturbed controls of either line. As expected, both the behavioral and physiological effects were more pronounced in HS than in LS birds. Struggling increased with repeated restraint in HS and LS quail, thus suggesting behavioral habituation to the stressor in both lines. On the other hand, a line effect on the pattern of adrenocortical responses was revealed upon subtracting the change in plasma C concentrations from Day 1 to Day 4 in the undisturbed controls from the corresponding change in restrained birds. Thus, unlike LS quail, in which there were no detectable effects of repeated restraint, the adrenocortical responses of HS birds showed evidence of experience-dependent sensitization. Our results demonstrate the importance of the background genome in determining the patterns of the behavioral and adrenocortical responses elicited by repeated exposure to stressful stimulation. The present results and those of previous studies could be explained in one or both of two ways: that underlying fearfulness is lower in LS than HS quail or that they adopt active or passive coping strategies, respectively. Our findings may also have important implications for poultry welfare and productivity. @ 2000 Elsevier Science Inc.

Adrenal Cortex↗
PubMed1995

Genetic selection for nicotine activity in mice correlates with conditioned place preference.

Genetically heterogenous stock (HS) mice are being used to develop lines which have differential locomotor response to subcutaneously administered (0.75 mg/kg) nicotine. These groups of nicotine-depressed, nicotine-activated or randomly bred control mice were tested as to conditioned place preference using the same dose of nicotine employed to determine their locomotor performance in activity tests. Results indicate that the nicotine-activated mice showed a significantly greater preference to nicotine when compared to the nicotine-depressed mice; this effect was seen in the first generation and continued in the more recently tested third generation. Evidence is offered to support the hypothesis that it is the stimulatory effects of drugs (of abuse) that can be directly correlatable with the strength of their reinforcing effect upon behavior.

Analysis of Variance↗
PubMed1999

Effect of genetic selection and MHC haplotypes on lymphocyte proliferation and interleukin-2 like activity in chicken lines selected for high and low antibody production against sheep red blood cells.

Chickens from third generation matings of lines of chickens selected for high (HA) and low (LA) antibody production to sheep red blood cells (SRBC) and typed for MHC genotypes B13/13, B13/21, and B21/21 were used in this study. Chickens from both lines carried all the three genotypes B13/13, B13/21, and B21/21. To study T- and B-lymphocytes mitogenic activity, 12-week-old female chickens were injected intravenously with 0.2 ml of 9% SRBC and spleens were collected at 0, 6 h, and 6 day post-antigen injection (pAg). Isolated lymphocytes were incubated with either Concanavalin-A (Con-A) for T-cell activity, or Pokeweed mitogen (PWM) for B-cell activity and thymidine 3H uptakes were measured. To study the Interleukin-2 (IL-2)-like activity in the same lines and genotypes, splenic lymphocytes from 12-week-old chickens were passed through nylon wool columns to enrich the T-cell population. After a 24 h incubation with Con-A, the conditioned media (CM) were collected. The CM were tested for IL-2 like activity by determining whether they altered the proliferation of Con-A stimulated T cells. This proliferation effect was then compared to that of a reference conditioned media (RCM) prepared from K-strain birds and that were used as the standard for the assay. There was no significant difference (p > 0.05) in IL-2 like activity between HA and LA lines, however, the LA was significantly higher than HA (p < 0.05) in T- and B-cell mitogenic activity. The genotype B13/13 had significantly higher (p < 0.05) IL-2 like activity than the B21/21. The genotype B13/13 was also significantly higher (p < 0.05) in T- and B-cell mitogenic activity than the B21/21. At 0 h, pAg T- and B-mitogenic activity was significantly higher (p < 0.05) than 6 h. In summary, our results indicate that although the birds were selected for high antibody production to SRBC, their lymphocyte mitogenic activity was lower than those selected for low antibody production. Hence, humoral and cell-mediated immune responses appear to be under different genetic controls, and that selection for greater humoral response may be at the expense of cellular responses. Our results also suggest differences in IL-2 like activity production between chickens carrying different MHC B-haplotypes, and that genetic control of such activity is possibly linked to the MHC genes.

Animals↗
PubMed2003

Ethics and genetic selection in purebred dogs.

There is an ongoing revolution in medicine that is changing the way that veterinarians will be counselling clients regarding inherited disorders. Clinical applications will emerge rapidly in veterinary medicine as we obtain new information from canine and comparative genome projects (Meyers-Wallen 2001: Relevance of the canine genome project to veterinary medical practice. International Veterinary Information Service, New York). The canine genome project is described by three events: mapping markers on canine chromosomes, mapping gene locations on canine chromosomes (Breen et al. 2001: Genome Res. 11, 1784-1795), and obtaining the nucleotide sequence of the entire canine genome. Information from such research has provided a few DNA tests for single gene mutations [Aguirre 2000: DNA testing for inherited canine diseases. In: Bonagura, J (ed), Current Veterinary Therapy XIII. Philadelphia WB Saunders Co, 909-913]. Eventually it will lead to testing of thousands of genes at a time and production of DNA profiles on individual animals. The DNA profile of each dog could be screened for all known genetic disease and will be useful in counselling breeders. As part of the pre-breeding examination, DNA profiles of prospective parents could be compared, and the probability of offspring being affected with genetic disorders or inheriting desirable traits could be calculated. Once we can examine thousands of genes of individuals easily, we have powerful tools to reduce the frequency of, or eliminate, deleterious genes from a population. When we understand polygenic inheritance, we can potentially eliminate whole groups of deleterious genes from populations. The effect of such selection on a widespread basis within a breed could rapidly improve health within a few generations. However, until we have enough information on gene interaction, we will not know whether some of these genes have other functions that we wish to retain. And, other population effects should not be ignored. At least initially it may be best to use this new genetic information to avoid mating combinations that we know will produce affected animals, rather than to eliminate whole groups of genes from a population. This is particularly important for breeds with small gene pools, where it is difficult to maintain genetic diversity. Finally, we will eventually have enough information about canine gene function to select for specific genes encoding desirable traits and increase their frequencies in a population. This is similar to breeding practices that have been applied to animals for hundreds of years. The difference is that we will have a large pool of objective data that we can use rapidly on many individuals at a time. This has great potential to improve the health of the dog population as a whole. However, if we or our breeder clients make an error, we can inadvertently cause harm through massive, rapid selection. Therefore, we should probably not be advising clients on polygenic traits or recommend large scale changes in gene frequencies in populations until much more knowledge of gene interaction is obtained. By then it is likely that computer modelling will be available to predict the effect of changing one or several gene frequencies in a dog population over time. And as new mutations are likely to arise in the future, these tools will be needed indefinitely to detect, treat and eliminate genetic disorders from dog populations. Information available from genetic research will only be useful in improving canine health if veterinarians have the knowledge and skills to use it ethically and responsibly. There is not only a great potential to improve overall canine health through genetic selection, but also the potential to do harm if we fail to maintain genetic diversity. Our profession must be in a position to correctly advise clients on the application of this information to individual dogs as well as to populations of dogs, and particularly purebred dogs.

Animals↗