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Results for “Selection, Genetic”

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PubMed1980

Cell-mediated immunity in Marek's disease virus-infected chickens genetically selected for high and low concentrations of plasma corticosterone.

Lines of chickens genetically selected for high (HPC)-and low-plasma corticosterone (LPC) titers were assessed for cell-mediated immunity during Marek's disease tumorigenesis. Lymphocyte transformation (using phytohemagglutinin and 2,4-dinitrofluorobenzene-bovine serum complex) and mitogen-induced cellular cytotoxicity were evaluated with peripheral blood leukocytes. Chickens from the LPC line showed a greater lymphocyte transformation response than those from the HPC line. All tumor-bearing chickens demonstrated a markedly suppressed blastogenic response. Although the blastogenic response was suppressed in those chickens infected with Marek's disease virus but not having gross tumors when compared with the steroid level, this response was greater than that of chickens with tumors and less than that of normal controls. In comparison with LPC-line chickens, HPC-line chickens demonstrated a decreased mitogen-induced cellular cytotoxicity. A decreased mitogen-induced cellular cytotoxicity was observed in both steroid lines concomitant with the onset and severity of tumors. The impaired cell-mediated response observed in the HPC line was associated with an increased tumor incidence and a greater mortality than that observed in the LPC line. Metyrapone, a chemical which blocks adrenal corticosterone synthesis, transiently enhanced mitogen-induced cellular cytotoxicity and initiated tumor regression in chickens debilitated with Marek's disease tumors.

Animals↗

PubMed1989

Sensitivity to the anticonvulsant effects of ethanol and pentobarbital in mouse lines genetically selected for ethanol sensitivity.

Mouse lines genetically selected for susceptibility [long sleep (LS)] or resistance [short sleep (SS)] to the acute hypnotic effects of ethanol were tested for sensitivity to maximal electroshock seizures. LS mice were slightly more sensitive than SS mice. Ethanol or pentobarbital pretreatment elevated seizure thresholds in both lines. LS and SS mice were approximately equally protected by ethanol, but LS mice were somewhat more protected than SS mice by pentobarbital. These studies do not provide evidence that sensitivity to the anticonvulsant effect of ethanol is mediated by substantially the same genes as those mediating sensitivity to EtOH's hypnotic effects. However, sensitivity to pentobarbital's anticonvulsant effects may be genetically correlated.

Animals↗

PubMed2004

Deciphering enzymes. Genetic selection as a probe of structure and mechanism.

The efficient engineering of enzymes with novel activities remains an ongoing challenge. Towards this end, genetic selection techniques provide a method for finding rare solutions to catalytic problems that requires only a limited foreknowledge of structure-function relationships. We have used genetic selections to extensively probe the structure and mechanism of chorismate mutases. The insights gained from these investigations will aid future enzyme design efforts.

Binding Sites↗

PubMed1989

Sensitivity and tolerance to ethanol-induced hypothermia in genetically selected mice.

COLD mice have been genetically selected for pronounced hypothermia (HT) after acute EtOH administration, whereas HOT mice have been selected for attenuated HT. In the current experiments, HOT and COLD mice were found to differ significantly in sensitivity to EtOH-induced HT across a range of doses: the difference was greater at higher doses. After 3 g/kg of EtOH, HOT mice displayed a 1.8 degrees C HT, whereas COLD mice had a 3.6 degrees C HT. Male mice had greater HT responses than female mice regardless of genotype. Nonselected control mice were intermediate to the HOT and COLD mice in responsiveness to EtOH. After an acute EtOH dose, HOT mice were found to have slightly lower brain EtOH concentrations than COLD mice 3 and 4 (but not 1 and 2) hr after administration of EtOH, and may have eliminated EtOH slightly more rapidly than COLD mice. When tested repeatedly in a cool ambient environment (18 degrees C), COLD mice developed tolerance to EtOH hypothermia, whereas HOT mice did not. These results confirm that sensitivity to the hypothermic effects of EtOH is influenced markedly by genotype. Furthermore, selection for neurosensitivity to EtOH has produced a correlated difference in rate or magnitude of tolerance development, which is consistent with an hypothesis of the influence of common genes determining these responses to EtOH. The difference in tolerance could not be accounted for by initial HT sensitivity differences between the lines. The HOT and COLD lines should be useful for studies of the neurobiological mechanisms of EtOH-induced HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1978

Risk factors in pigeons genetically selected for increased atherosclerosis susceptibility.

A strain of genetically selected White Carneau pigeons (WC-2) with increased atherosclerosis at similar plasma cholesterol concentrations as randomly bred (RBWC) pigeons was studied to evaluate the commonly known risk factors for atherosclerosis. Indicators for the presence of hypertension, diabetes mellitus, "stress", hyperuricemia and hypothyroidism were determined. In pigeons fed the atherogenic diet, major differences in atherosclerosis were seen between WC-2 and RBWC. WC-2 pigeons had more aortic surface covered with plaque and greater concentrations of aortic nonesterified cholesterol, esterified cholesterol, uronic acid, and hydroxyproline, as well as a greater prevalence and severity of coronary artery atherosclerosis. For WC-2 and RBWC pigeons we found similar levels of hypercholesterolemia, mean blood pressure, plasma triglyceride and glucose concentrations. In addition, several other physiological variables such as plasma uric acid, calcium and phosphorus concentrations, adrenal and thyroid weights which have been implicated in the pathogenesis of atherosclerosis were similar. The findings indicate that the differences in extent and severity of atherosclerosis between WC-2 and RBWC cannot be explained by differences in the risk factors studied. Possible genetic regulation of atherosclerosis by mechanisms operable in the arterial wall of WC-2 pigeons is suggested.

Animals↗

PubMed1990

Effects of genetic selection on growth rate and intestinal structure in the domestic fowl (Gallus domesticus).

1. Pieces of small intestine taken from chickens subjected previously to continuous selection, relaxed selection or no selection for rapid growth were used to estimate villus surface area and microvillus development to determine what effects genetic selection might have on factors controlling intestinal function. 2. Crypt size and the rates at which enterocytes migrated out of crypts were also measured, after injection of tritiated thymidine, to determine the time course of microvillus elongation. 3. Differences in growth rates measured between highly selected, relaxed selected or unselected birds were found to be correlated with parallel changes in villus surface area. Selection for growth did not change the density, dimensions or pattern of development of enterocyte microvilli. Microvilli did, however, produce a maximal 20-fold increase in villus surface area under all conditions. 4. Crypt size and enterocyte migration rates did not vary significantly between tissue taken from unselected and relaxed selected chickens. Tissue taken from highly selected birds had a crypt size and enterocyte migration rate 40% higher than values found for the other two groups of chickens. 5. The possibility that early genetic selection increased growth potential by uncoupling diet-induced changes on crypt hyperplasia from secondary effects on villus structure, and that later selection increased growth potential by increasing appetite, is discussed.

Animals↗

PubMed1997

Genetic selection strategies: computer modeling.

There are four primary factors to consider in genetic selection strategies: 1) accuracy of selection, 2) selection intensity, 3) effective population size, and 4) mating system. Current theory indicates that optimum response to selection is achieved by maximizing the first three factors and using a mating systems that allows optimization of reproductive characteristics in dam lines and production characteristics in sire lines. However, with limited resources, compromises among the first three factors are needed. Simulations are useful for examining those compromises. Unrealistic simplifying assumptions are necessary for analytic theoretical results and thus do not address real world breeding problems. Using simulations, the relationship between selection accuracy, which is increased by use of family selection indices or Best Linear Unbiased Prediction (BLUP), and response to selection was examined. Results show that those procedures place a great restriction on effective population size, which offsets most of their advantage, i.e., there is too little emphasis on effective population size. A revision of the methodology and a reappraisal of the results of selection theory for optimization of genetic response is required. Another relationship that is of fundamental importance in breeding programs is that between selection intensity and effective population size. Analytical results for the additive case have been developed but have never been extended to heterotic traits. A gene level simulation program was developed to examine that relationship. Results show that the optimal selection strategy depends on the trait being selected. For additive traits and in the short term (20 generations), one should maximize selection intensity. For heterotic traits, an intermediate proportion (25% of each sex) gives optimal response. In all breeding strategies, primary attention must be given to the rate of inbreeding, which is increased by increasing either accuracy of selection or selection intensity. Inbreeding reduces response to selection in two ways. First, for both additive and nonadditive traits, inbreeding is a measure of the amount of random genetic drift that has occurred. Genetic drift causes loss of favorable alleles. Once lost, those alleles can never be recovered and thus genetic drift lowers the selection limit. Second, for heterotic traits, inbreeding results in a depression of the mean caused by directional dominance.

Animals↗

PubMed1998

Vectors for transcription factor cloning and target site identification by means of genetic selection in yeast.

We describe the construction of a number of vectors that can be used in yeast genetic selection systems for cloning of transcription factors or other DNA-binding proteins and for identification of the target sites recognized by transcription factors. For transcription factor cloning we have designed an integration vector with two HIS3 reporter gene cassettes to stably integrate reporter gene constructs at the non-essential yeast PDC6 locus. This set of plasmids was tested in a one-hybrid assay with the rice transcription factor Oshox1, a member of the class of homeodomain leucine zipper proteins. A hybrid protein of Oshox1 and the Gal4 transcriptional activation domain was shown to specifically activate a reporter gene construct with upstream Oshox1 binding sites, which had been integrated at the PDC6 locus using the described vector system. Target site identification by genetic selection in yeast employs a transcriptional activator construct and a library of genomic or random DNA fragments upstream of a reporter gene. We have constructed two variants of a bacteriophage lambda vector which facilitates the construction of the required reporter gene library because of high cloning efficiency and easy conversion into a yeast/Escherichia coli shuttle vector library by Cre-loxP-mediated automatic subcloning. Tests with Oxhox1 as transcriptional activator demonstrated the usefulness of the deprived reporter gene vector.

Bacteriophage lambda↗

PubMed2000

Influence of genetic selection for antibody production against sheep blood cells on energy metabolism in laying hens.

Genetic selection in chickens has been utilized to enhance immune responses that may influence resistance to diseases. It is important, however, to investigate the effects of this selection on other physiological processes. Therefore, this study was conducted to determine whether selection for antibody (Ab) production against SRBC has an effect on energy metabolism. Laying hens from three lines were used in this study, two of which were selected for 15 generations for Ab response against SRBC, and the third was nonselected and randombred. The hens used were from four different groups. The first two groups were from the lines that were selected for either high (SH) or low (SL) Ab production. The second two groups were control birds (nonselected) that had either high (CH) or low (CL) Ab titers that were similar to those in the SH and SL lines, respectively. The birds were housed in climate-respiration chambers. Body weights and energy metabolism were measured. Body weights of SL hens were significantly (P < 0.05) higher than those of SH hens. However, the BW for the two nonselected groups were similar but significantly less than the SL group. Energy partitioning was similar in all groups; however, ME for maintenance for the selected groups (119 kcal x kg(-0.75 x d(-1)) was numerically, but not significantly (P < 0.09), higher than that of the nonselected groups (112 kcal x kg(-0.75) x d(-1)). These results suggest that divergent selection for Ab may result in an increase in the requirements of energy for maintenance, which is not directly related to the amount of Ab produced. Furthermore, these results support previous findings of the presence of a negative correlation between BW and the levels of Ab in selected lines.

Animals↗

PubMed2001

The effects of genetic selection on production parameters of single comb White Leghorn hens.

Four commercial table egg genetic stocks consisting of the Ottawa Control Strains 5, 7, and 10 (CS5, CS7, and CS10) and the 1993 H&N "Nick Chick" (CCS) were housed in the same environment and compared for production characteristics. These birds were housed in an environmentally controlled laying facility with trideck cages. Feed consumption, egg production, and mortality were monitored daily and compiled every 28 d. The study was conducted for two egg production cycles, including the molt period. Body weight was progressively lower for the more modern strains with CS5 being the heaviest and CCS maintaining the smallest body weight throughout the production periods. The CCS had the highest (P < 0.0001) hen-day production rate, which resulted in the greatest daily egg mass among the strains. The CCS consumed the greatest amount of feed and exhibited the highest gross egg income among the strains. We concluded that genetic selection has improved production parameters in commercial layers as determined by measurements in this study.

Animals↗

PubMed1998

Dissection of signaling pathways and cloning of new signal transducers in tyrosine kinase-induced pathways by genetic selection.

We used genetic strategies which have been proven valuable to decipher signaling pathways in comparatively simple organisms such as Drosophila and Caenorhabditis elegans, to dissect signaling network activated by tyrosine kinases in mammals. The strategy was developed further towards a generally applicable expression cloning system to identify signal transducers in tyrosine kinase pathways. This system is based on the ability of downstream acting genes to rescue the transformation phenotype of partial loss-of-function mutants of BCR-ABL which still retain tyrosine kinase activity. Using this strategy we have previously shown that overexpression of c-Myc and Cyclin D1 can rescue a signaling defective SH2 mutant of BCR-ABL for transformation. In an unbiased approach to identify new compensating genes, a cDNA library was introduced by retroviral infection into fibroblasts which express the BCR-ABL SH2 mutant. CDNA clones, capable of rescuing the SH2 mutant for transformation should result in colony formation in soft agar. A PCR approach was used to recover these compensating genes from the genomic DNA of the transformed fibroblasts. Sequencing analysis of the initial cDNAs identified three known genes, the adapter molecule Shc, the kinases SPRK and p38 MAPK. These genes have been found to interact functionally with BCR-ABL for fibroblast and hematopoietic cell transformation. Currently, we are constructing and screening new libraries to identify novel genes which complement the BCR-ABL SH2 mutant. Our results demonstrate that this cloning approach is an effective means of identifying and characterizing signaling molecules that function in specific signaling pathways. This in turn may identify specific targets for mechanism-based therapeutic intervention to block altered signaling.

Adaptor Proteins, Signal Transducing↗

PubMed1979

Some models of genetic selection.

This paper begins with a description of the classical theory of viability selection in which probabilities that individuals of various genotypes survive are in proportions that do not change with time and are independent of population structure. Salient features of viability selection with one and two loci are reviewed. This theory is intimately connected with the usual theory of mass selection in quantitative genetics. It is well known that the mean of the relative viabilities does not necessarily increase if there is viability selection at more than one locus. It also turns out that if there is selection for fecundity with one locus, the mean fecundity may steadily decrease or oscillate rather than increase. This and the fact that a Hardy-Weinberg structure may no longer exist at any stage of life may have a bearing on predicting progress from artificial selection on reproductive characters. Classical viability selection theory does not completely describe natural selection. Other possibilities are discussed. Among these is the density and frequency dependent selection induced when the population lives in a limited habitat. Implications in quantitative genetics are discussed.

Alleles↗

PubMed1994

Genetic selection of meiotic and mitotic recombinant yeast artificial chromosomes.

We have developed a genetic screen for the isolation of larger or smaller recombinant yeast artificial chromosomes derived from overlapping YACs. Integration plasmids were used to modify the TRP1 and URA3 auxotrophic markers present respectively on the left and right vector arms of one of the parental YACs. Diploids containing the two parental YACs were studied through meiosis and mitosis. Tetrad analysis revealed the presence of meiotic recombinant YACs at a frequency comparable with what is expected for yeast DNA (about 3 kb/cM). More direct genetic selection of diploids on -TRP-LYS synthetic media in the presence of 5-fluoro-orotic acid (5-FOA), led to the isolation of mitotic recombinant YACs at a high frequency. Analysis of these yeast cells by pulsed-field gel electrophoresis, confirmed the loss of both parental artificial chromosomes, and the specific retention of a larger or smaller recombinant YAC.

Animals↗

PubMed1993

Resistance of genetically selected mice to MHV3 infection is not dependent on the H2O2 release by macrophages.

The genetically selected high antibody responder line of mice (HIII) for a natural immunogen were fully susceptible to mouse hepatitis virus 3 (MHV3) and the corresponding low antibody responder mice (LIII) were fully resistant, regardless of whether they were previously treated or not with the bacillus Calmette-Guérin (BCG). The resistance or susceptibility correlated with the virus growth in the peritoneum of mice. Peritoneal cells isolated from resistant mice released higher amounts of H2O2 after phorbol myristate acetate (PMA) stimulation than susceptible mice. No spontaneous in vitro H2O2 release by peritoneal exudate cells from HIII mice, shown to be mostly macrophages, were observed during the MHV3 infection. In contrast, the spontaneous in vitro H2O2 release by these cells from MHV3-infected LIII mice increased gradually, reaching a maximal value 3 days after infection, and decreased in parallel to the virus clearance from the peritoneum. The BCG treatment primed the macrophages of HIII mice for the production of H2O2 during the MHV3 infection, but did not confer resistance against the virus infection. The data obtained suggest that the acquired capability of macrophages to release H2O2 does not participate in the anti-MHV3 activity or resistance against the MHV3 infection.

Animals↗

PubMed1998

Improving animal well-being through genetic selection.

This paper reviews the possibilities of adapting laying hens to cages by means of genetic selection. By selecting separately for rate of lay and longevity using a kin selection method, a strain of laying hen has been developed that shows much less feather pecking and cannibalism than a control strain, and with no decrease in productivity. This experimental strain enjoys a higher level of welfare in cages because it does not require beak trimming.

Adaptation, Physiological↗

PubMed1994

Genetic selection for mutations that impair the co-operative binding of lambda repressor.

Bacteriophage lambda repressor binds co-operatively to adjacent pairs of DNA target sites. A novel combination of positive genetic selections, involving two different operon fusions derived from P22 challenge phages, was used to isolate mutant lambda repressors that have lost the ability to bind co-operatively to tandem sites yet retain the ability to bind a strong, single site. These cb (co-operative binding) mutations result in 10 different amino acid changes, which define eight residues in the carboxyl-terminus of repressor. Because challenge phage derivatives may be applied to study essentially any specific protein-DNA interaction, analogous combinations of genetic selections may be used to explore the ways that a variety of proteins interact to assemble regulatory complexes.

Amino Acid Sequence↗

PubMed2006

Prospects for improving reproductive performance through genetic selection.

Prospects for improving female fertility in dairy cattle using genetic selection are reviewed. Today's high producing cows have shorter estrous cycles, fewer standing events, shorter duration of estrus, and more frequent multiple ovulations. Although high milk production is often implicated as the cause of impaired fertility, the impact of inadequate body condition appears to be greater, as the latter has a significant impact on probability of conception, rate of embryonic loss, and proportion of anestrous animals. Genetic improvement of female fertility can be achieved by indirect selection for longevity or body condition score, or by direct selection for traits such as daughter pregnancy rate. Most leading dairy countries have implemented genetic evaluation systems for female fertility in the past decade, but refinement of these systems to account for hormonal synchronization, differences in the voluntary waiting period, exposure to natural service bulls, and other confounding factors is warranted. Recent work has focused on the development of data collection and genetic evaluation systems that will allow selection of bulls that have daughters that are resistant to common health disorders, including mastitis, lameness, ketosis, displaced abomasum, and metritis. Such systems will allow selection of animals that can remain healthy and fertile while producing large quantities of milk.

Animals↗

PubMed2003

Genetic selection for coping style predicts stressor susceptibility.

Genetically selected aggressive (SAL) and nonaggressive (LAL) male wild house-mice which show distinctly different coping styles, also display a differential regulation of the hypothalamic-pituitary-adrenal axis after exposure to an acute stressor. To test the hypothesis that coping style predicts stressor susceptibility, the present study examined line differences in response to a chronic stressor. Chronic psychosocial stress was evoked using two paradigms. In the first paradigm, a SAL or LAL male was living in sensory contact (except tactile contact) with a dominant SAL male for 25 days (sensory contact stress). In the second paradigm, a SAL or LAL male was, in addition to the first paradigm, defeated by a SAL male for 21 consecutive days (defeat stress). The sensory contact stressor induced in LAL mice chronic body weight loss and increased plasma adrenocorticotropic hormone levels compared to SAL mice and increased corticosterone levels, thymus involution and lower hippocampal mineralocorticoid receptor (MR) : glucocorticoid receptor (GR) ratio compared to LAL controls. The defeat stressor increased corticosterone secretion and caused adrenal hypertrophy and thymus involution in both mouse lines. Defeated LAL mice showed long-lasting body weight loss and higher corticosterone concentrations than SAL mice and lower hippocampal MR : GR ratio and decreased immobility behaviour in the forced swimming test than LAL controls. Hypothalamic corticotropin-releasing hormone mRNA expression was higher in defeated SAL than in controls. The present data show that both stress paradigms induced line-dependent physiological and neuroendocrine changes, but that the sensory contact stressor produced chronic stress symptoms in LAL mice only. This latter stress paradigm therefore seems promising to analyse the role of genetic factors in the individual differences in stress-related psychopathology.

Adaptation, Psychological↗