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Trichinella infestation in mice genetically selected for high and low antibody production.

Mice genetically selected according to their capacity to produce antibodies (high and low responder lines) were infested with Trichinella spiralis. High responder mice produced much higher levels of IgE and gamma1 serum antibodies than low responder mice. IgG and IgM antibodies were detected by immunodiffusion analysis or passive haemagglutination only in animals of the high responder line and in very low concentrations. The number of living larvae present in the muscles was very similar in the animals of both lines 30, 60 or 75 days after infestation.

Animals↗

Alcohol intake is inversely related to plasma renin activity in the genetically selected alcohol-preferring and -nonpreferring lines of rats.

Studies involving both animals and humans strongly suggest that alcoholism is, in part, genetically determined. One approach to studying this genetic component is to determine whether rats, genetically selected to prefer (P line) or avoid (NP line) alcohol, show differences in those physiological systems which modulate alcohol intake. It has previously been shown that alcohol intake in randomly bred stock rats is sensitive to and inversely related to manipulations which alter activity in the renin-angiotensin (R-A) system. In the present report the basal level of activity in the R-A systems of the P and NP rats as measured by plasma renin activity (PRA) was first assessed following which continuous access to alcohol (10% v/v) and water was offered for a period of five days. PRA was found to be inversely related to the amount of alcohol that was consumed. The P rats drank significantly larger amounts of alcohol than the NP rats who basically avoided the drug. The P rats had a significantly lower PRA than the NP rats. It is suggested that the genetic selection that favored different levels of alcohol consumption in the P and NP rats may have brought about this effect through differences in the activity of the renin-angiotensin systems in the two lines.

Alcohol Drinking↗

Genetic selection for health traits using producer-recorded data. II. Genetic correlations, disease probabilities, and relationships with existing traits.

The objectives of this study were to calculate genetic correlations between health traits that were recorded in on-farm herd management software programs and to assess relationships between these traits and other traits that are routinely evaluated in US dairy sires. Data consisted of 272,576 lactation incidence records for displaced abomasum (DA), ketosis (KET), mastitis (MAST), lameness (LAME), cystic ovaries (CYST), and metritis (MET) from 161,622 cows in 646 herds. These data were collected between January 1, 2001 and December 31, 2003 in herds using the Dairy Comp 305, DHI-Plus, or PCDART herd management software programs. Binary incidence data for all disorders were analyzed simultaneously using a multiple-trait threshold sire model that included random sire and herd-year-season of calving effects. Although data from multiple lactations were available for some animals, our genetic analysis included only first parity records due to concerns about selection bias and improper modeling of the covariance structure. Heritability estimates for the presence or absence of each disorder during first lactation were 0.14 for DA, 0.06 for KET, 0.09 for MAST, 0.03 for LAME, 0.04 for CYST, and 0.06 for MET. Estimated genetic correlations were 0.45 between DA and KET, 0.42 between KET and CYST, 0.20 between MAST and LAME, 0.19 between KET and LAME, 0.17 between DA and CYST, 0.17 between KET and LAME, 0.17 between KET and MET, and 0.16 between LAME and CYST. All other correlations were negligible. Correlations between predicted transmitting abilities for the aforementioned health traits and existing production, type, and fitness traits were low, though it must be noted that these estimates may have been biased by low reliability of the health trait evaluations. Based on results of this study, it appears that genetic selection for health disorders recorded in on-farm software programs can be effective. These traits can be incorporated into selection indices directly, or they can be combined into composite traits, such as "reproductive disorders", "metabolic disorders", or "early lactation disorders".

Abomasum↗

Direct genetic selection of two classes of R17/MS2 coat proteins with altered capsid assembly properties and expanded RNA-binding activities.

RNA challenge phages are derivatives of bacteriophage P22 that enable direct genetic selection for a specific RNA-protein interaction. The bacteriophage P22 R17 encodes a wild-type R17 operator site and undergoes lysogenic development following infection of susceptible bacterial strains that express the R17/MS2 coat protein. A P22 R17 derivative with an OcRNA site (P22 R17 [A(-10)U]) develops lytically following infection of these strains. RNA challenge phages can be used to isolate second-site coat protein suppressors that recognize an OcRNA sequence by selecting for lysogens with a P22 R17 [Oc] phage derivative. The bacteriophage derivative P22 R17 [A(-10)U] was used in one such scheme to isolate two classes of genes that encode R17 coat proteins with altered capsid assembly properties and expanded RNA-binding characteristics. These mutations map outside the RNA-binding surface and include amino acid substitutions that interfere with interactions between coat protein dimers in the formation of the stable phage capsid. One class of mutants encodes substitutions at the highly conserved first and second positions of the mature coat protein. N-terminal sequence analysis of these mutants reveals that coat proteins with substitutions only at position 1 are defective in post-translational processing of the initiator methionine. All selected proteins possess expanded RNA-binding properties since they direct efficient lysogen formation for P22 R17 and P22 R17 [A(-10)U]; however, bacterial strains that express the protein mutants remain sensitive to lytic infection by other P22 R17 [Oc] bacteriophages. The described selection strategy provides a novel genetic approach to dissecting protein structure within RNA-binding proteins.

Amino Acid Sequence↗

Genetic selection in Escherichia coli for active human immunodeficiency virus reverse transcriptase mutants.

Most catalytically active human immunodeficiency virus (HIV) reverse transcriptase (RT) mutants characterized to date have been isolated from the virus after treatment with HIV RT inhibitors such as nucleoside analogs. However, detailed understanding of structure-function relationships, and of the roles of the several catalytic activities of HIV RT in viral replication, requires characterization of a greater diversity of mutant enzymes than has been obtained from viral variants. Coupling of a bacterial genetic selection system for functional HIV RT with random mutagenesis has yielded a large number of active mutant enzymes, most of which have not been found in viral variants. The genetic selection system, combined with biochemical characterization of active mutant proteins, affords three major benefits. First, we can increase our understanding of the roles of individual amino acids in catalysis. Second, the mutational spectrum observed among active HIV RT variants can identify amino acids that are intolerant, or relatively intolerant, of substitution. Third, this system provides us with HIV RT variants with altered biochemical properties, such as replicational fidelity and processivity. Characterization of HIV harboring these mutant RTs with defined structural and functional alterations will contribute to elucidation of the roles of each catalytic activity of HIV RT in viral replication.

Chromatography, Affinity↗

A reparameterization of a genetic selection index to locate its sampling properties.

A transformation is proposed of the variables used for constructing genetic selection indices, such that the reparameterized phenotypic covariance matrix is identity and the genetic covariance matrix is diagonal. These diagonal elements play the role of heritabilities of the transformed variables. The reparameterization enables sampling properties of the index weights to be easily computed and formulae are given for data from half-sib families. The index is likely to be least stable when the transformed variables of low heritability have high economic weights, and the weights will have highest sampling variance when these heritabilities are nearly equal. It is suggested that the sample roots of the determinantal equation be inspected when constructing an index in order to give some guide to its accuracy.

Genetic Variation↗

Threat-induced behavioural inhibition in Japanese quail genetically selected for contrasting adrenocortical response to mechanical restraint.

1. Behavioural and adrenocortical responses to brief mechanical restraint were examined in 28-d-old female Japanese quail of two lines which had been genetically selected over several generations for either reduced (LS, low stress) or exaggerated (HS, high stress) plasma corticosterone response to brief immobilisation in a metal box. 2. As expected, quail of the LS line showed lower adrenocortical responses to restraint than did their HS line counterparts. The LS quail also struggled much sooner and more often during the 5 min restraint period than did the HS ones. Collectively, these and previously reported line differences in behavioural, catecholamine and adrenocortical responsiveness are consistent with an interpretation based on the adoption of active and passive coping strategies respectively by LS and HS quail upon their exposure to alarming stimuli.

Adrenal Cortex↗

Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus).

An animal model was developed to study effects on components of exercise physiology of both "nature" (10 generations of genetic selection for high voluntary activity on running wheels) and "nurture" (7-8 wk of access or no access to running wheels, beginning at weaning). At the end of the experiment, mice from both wheel-access groups were significantly lighter in body mass than mice from sedentary groups. Within the wheel-access group, a statistically significant, negative relationship existed between activity and final body mass. In measurements of maximum oxygen consumption during forced treadmill exercise (VO2max), mice with wheel access were significantly more cooperative than sedentary mice; however, trial quality was not a significant predictor of individual variation in VO2max. Nested two-way analysis of covariance demonstrated that both genetic selection history and access to wheels had significant positive effects on VO2max. A 12% difference in VO2max existed between wheel-access selected mice, which had the highest mass-corrected VO2max, and sedentary control mice, which had the lowest. The respiratory exchange ratio at VO2max was also significantly lower in the wheel-access group. Our results suggest the existence of a possible genetic correlation between voluntary activity levels (behavior) and aerobic capacity (physiology).

Aerobiosis↗

Genetic selection for genes encoding sequence-specific DNA-binding proteins.

We describe a genetic selection method designed to facilitate the cloning of genes encoding sequence-specific DNA-binding proteins. The strategy selects for clones expressing particular sequence-specific DNA-binding activities from a library of clones encoding other, nonspecific proteins. Specific DNA-binding sites have been placed near the start of transcription of the strong synthetic conII promoter to create promoters that can be repressed by the corresponding sequence-specific DNA-binding proteins. Transcription from the conII derivatives in the absence of repression interferes with the phenotypic expression of an adjacent drug-resistance gene, aadA. Sequence-specific DNA-binding proteins are shown to repress these promoters and alleviate transcriptional interference of aadA, resulting in drug resistance in cells expressing the appropriate DNA-binding protein.

Animals↗

Differential expression of migration inhibitory and migration stimulatory factors in two lines of mice genetically selected for high or low responsiveness to phytohemagglutinin. 2. Effects of mitogenic or allogeneic stimulation.

Expression of migration inhibition factor (MIF) following in vitro stimulation with phytohemagglutinin (PHA) or allogeneic cells was explored in two lines of mice genetically selected for the high (Hi/PHA) or low (Lo/PHA) response of their lymphoid cells to PHA. Hi/PHA mice also have greater cell-mediated immune responses in mixed lymphocyte culture and graft-versus-host reactions, the poorer cell-mediated immune response of Lo/PHA being accompanied by a higher frequency of malignant tumours. Expression of MIF in PHA-pulsed spleen cell supernatants measured by a sensitive photoelectric method was found to be modulated by the concomitant presence of migration stimulation factor (MStF) derived from T cells. Both lymphokines were better expressed in Lo/PHA, as compared to Hi/PHA, under appropriate experimental conditions. Use of a low proliferative dose of mitogen (5 micrograms/ml PHA, 2-hour pulse) followed by culture in serum-free medium led Lo/PHA to express the highest titres of MIF, whereas a proliferative dose of PHA (50 micrograms/ml, 2-hour pulse) caused abrogation or occultation of expression of MIF and elective expression of MStF in this line. Hi/PHA mice expressed MIF equally at both mitogen doses, with transient expression of MStF followed by MIF after 50 micrograms/ml PHA, the kinetics of expression of the two lymphokines being different. Expression of MStF by spleen cells was an early event after PHA stimulation. In contrast to mitogenic stimulation, allogeneic stimulation in one-way mixed lymphocyte culture led to similar expression of MIF by both lines of mice. The implications of these findings are discussed.

Animals↗

A genetic selection for supercoiling mutants of Escherichia coli reveals proteins implicated in chromosome structure.

Chromosomes are divided into topologically independent regions, called domains, by the action of uncharacterized barriers. With the goal of identifying domain barrier components, we designed a genetic selection for mutants with reduced negative supercoiling of the Escherichia coli chromosome. We employed a strain that contained two chromosomally located reporter genes under the control of a supercoiling-sensitive promoter and used transposon mutagenesis to generate a wide range of mutants. We subjected the selected mutants to a series of secondary screens and identified five proteins as modulators of chromosomal supercoiling in vivo. Three of these proteins: H-NS, Fis and DksA, have clear ties to chromosome biology. The other two proteins, phosphoglucomutase (Pgm) and transketolase (TktA), are enzymes involved in carbohydrate metabolism and have not previously been shown to affect DNA. Deletion of any of the identified genes specifically affected chromosome topology, without affecting plasmid supercoiling. We suggest that at least H-NS, Fis and perhaps TktA assist directly in the supercoiling of domains by forming topological barriers on the E. coli chromosome.

Bacterial Proteins↗

Responses to the change in the environment in pairs of male rats genetically selected for activity level.

Laboratory Wistar strain rats were genetically selected for high (+A) and low (-A) activity level. In thirteen pairs of adult males of the 23rd filial generation reactions to changes in the external environment were studied. The animals were housed in breeding cages four each. Two parallel studies were conducted: in pairs simultaneously placed into a novel environment (NOV), empty cages of the same dimensions as the home cage (HC), in the second, behaviour of the second pair that remained in the HC, after removal of two cage-mates, was tested. Once a minute, for a period of one hour, the type of activity was recorded and noted whether it was an element effected in contact with the partner or without any contact. The animals +A and -A differed in the frequency of various types of activity and immobility, in the ratio between behavioural manifestations shown in or without contact as well as in the response to the type of modified environment. To changes in the situation, whether removed cage-mates from the HC or placed into NOV +A animals reacted with a high wave of environment exploration which gradually habituated. -A rats equally responded with exploration but on a lower level. In +rats we recorded more frequently exploration without contact with the partner in HC and NOV in comparison with -A, more frequent grooming, less immobility in contact and with no contact. Between +A partners there was a greater number of contacts in NOV than in HC whereas in the -A group the incidence of contact did not differ between HC and NOV. ANOVA revealed the influence of factors of genetics and environment and interaction in several behavioural categories. The simple and in time economical method demonstrated the possibility of use for the detection of differences between +A and -A lines even at relatively small changes in the external stimulatory situation.

Animals↗

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol.

Cortical electroencephalographic (EEG) changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbital, which again parallels previous behavioral data. The SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS mice; a continuous iv infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS mice. The lines do not differ in rate of nicotine metabolism, hence they must differ in central nervous system sensitivity to nicotine. Thus, lines of mice selectively bred for differential sensitivity to ethanol also display marked differences in electrophysiological and behavioral responses to nicotine.

Animals↗

Aortic glycosaminoglycans in genetically selected WC-2 pigeons with increased atherosclerosis susceptibility.

A genetically selected line of White Carneau pigeons (WC-2) was studied in an attempt to relate changes in composition and content of aortic glycosaminoglycan (GAG) to increased atherosclerosis susceptibility. The WC-2 pigeons were fed an atherogenic diet for 3 months and, when compared to randomly bred White Carneau (RBWC) controls, they showed similar plasma cholesterol concentrations but significantly greater aortic atherosclerosis. In the WC-2 pigeons, 35% of the aortic surface was covered with plaque compared with only 12% in RBWC pigeons; WC-2 birds showed cholesterol contents of 3.3 mg/aorta/500 g body weight, while the RBWC birds had only 0.9 mg/aorta/500 g body weight. After papain treatment of delipidated dried artery, the aortic GAG were isolated, purified using cetylpyridinium chloride, and identified and quantitated by a combination of procedure including selective enzymatic digestion and electrophoresis. In both pigeon groups, aortic GAG included 8% hyaluronic acid, 11% dermatan sulfate, 15% heparan sulfate, and 66% chondroitin sulfate. For the entire group, total aortic GAG content was 35% greater in WC-2 pigeons. Since we did not know if this increase in GAG was simply due to increased atherosclerosis in the WC-2 birds, we sorted the pigeons into matched groups representing minimal, moderate, and severe atherosclerosis on the basis of aortic cholesterol content. At all levels of cholesterol, all GAG contents were greater in the aortas of WC-2 pigeons. The accumulation of dermatan sulfate was 30% higher than in RBWC birds in the minimal arteriosclerosis group, 101% higher in the moderate group, and 53% higher in the severe group. Hyaluronic acid tended to decrease as aortic cholesterol contents increased in WC-2 pigeons. Reduced hyaluronic acid and increase dermatan sulfate may suggest the presence of an altered hyaluronic acid-dermatan sulfate-containing proteoglycan aggregate in the intercellular matrix of the WC-2 pigeon aorta. Possible consequences include increased artery permeability and a binding and retention of lipoproteins in the artery wall. These factors may explain why atherosclerosis develops at an increased rate in the WC-2 pigeon.

Animals↗

Male sex hormone and nephropathy in Cohen diabetic rat. (Genetically selected sucrose fed).

In the Cohen diabetic rat (genetically-selected sucrose fed) ovariectomy caused a significant decrease in the incidence of nephropathy, from 52% in the unovariectomized, to 16% in the ovariectomized rat, [X2 (d.f. = 1) = 7.21905 P/0.01]. Testosterone administration to the ovariectomized diabetic animal resulted in a significantly increased incidence of nephropathy, from 16 to 92% [X2 (d.f. = 1) = 28.04427 P/0.01]. This change in incidence of nephropathy was directly correlated with a corresponding decrease or increase in the plasma oestradiol levels (in the ovariectomized and in the ovariectomized-testosterone treated diabetic animals, respectively). No such correlation was found with carbohydrate metabolism disturbances (as demonstrated by spontaneous blood glucose and spontaneous insulin) or with plasma testosterone levels.

Animals↗

Genetic selection and the status of the embryo.

In this paper I want to try to clarify the nature of the two different problems indicated in the title: there is a lively debate on whether or not genetic selection is a morally licit practice, and there are strong disagreements on whether or not the embryo is a person. I think that most of such controversies depend on confusions and/or unclearness about specific problems involved in each issue, I have no precise normative proposal on the morality of genetic selection, but I hope that my analysis will be helpful in avoiding some current confusions.

Abortion, Eugenic↗

Food intake response of genetically selected high and low-weight line cockerels to plasma infusions from fasted fowl.

Two experiments were conducted to determine if food intake of free-feeding chickens could be affected by infusions of plasma from fasted fowl. In the first experiment, chickens from two lines genetically selected for high or low body weight were infused intrahepatically with plasma collected from free-fed and fasted individuals from each line. Food intake of low-weight line birds was increased significantly by infusions of plasma from fasted high-weight line chickens when compared to food intake of low-weight line birds receiving plasma from free-fed low-weight line chickens. Food consumption in high-weight line birds was unaffected by any of the plasma treatments. In the second experiment, plasma from free-fed and fasted high-weight line chickens was infused intrahepatically into Single Comb White Leghorn cockerels. Again the birds receiving the plasma from the fasted fowl consumed significantly more food than those infused with plasma from free-fed fowl. The results of these experiments suggest that some property of plasma from fasted birds stimulates appetite. Selection for increased body weight may have intensified this hunger factor in high weight fowl.

Animals↗

Beneficence, determinism and justice: an engagement with the argument for the genetic selection of intelligence.

In 2001, Julian Savulescu wrote an article entitled 'Procreative Beneficence: Why We Should Select the Best Children', in which he argued for the genetic selection of intelligence in children. That article contributes to a debate on whether genetic research on intelligence should be undertaken at all and, if so, should intelligence selection be available to potential parents. As such, the question of intelligence selection relates to wider issues concerning the genetic determinism of behavioural traits, i.e. alcoholism. This article is designed as an engagement in the intelligence selection debate using an analysis of Savulescu's arguments to raise a series of problematic issues in relation to the ethics of parental selection of intelligence. These problematic issues relate to wider assumptions that are made in order to put forward intelligence selection as a viable ethical option. Such assumptions are more generic in character, but still relate to Savulescu's article, concerning issues of genetic determinism, private allocation and inequality, and, finally, individual versus aggregate justice. The conclusion focuses on what the implications are for the question of agency, especially if intelligence selection is allowed.

Beneficence↗