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Genetic analysis of the behavioral response to d-amphetamine in mice.

The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57BL/10J, and C57BL/6By. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C57BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although the genetic analysis is not conclusive, it appears to be compatible with regulation by a single major gene. The two single-gene models reported here (one affecting the stimulatory response and the other the inhibitory response to d-amphetamine) may be useful in the study of neural mechanisms involved in stimulation and inhibition of behavior by d-amphetamine.

5-Hydroxytryptophan

Genetic analysis of cell malignancy--evidence from somatic cell genetics.

When normal nontumorigenic cells are fused with tumorigenic cells some of the resulting hybrids are nontumorigenic in respect to their ability to grow in immune-deficient nude mice. Comparison of the chromosome content of nontumorigenic with tumorigenic hybrids, as well as with the cells of tumors which develop from the latter, reveals that in normal human x tumorigenic Chinese hamster hybrid crosses, two specific human chromosomes of the nontumorigenic parental line are very likely responsible for the suppressive effect. In some other hybrid crosses these and additional human chromosomes also seem to cause suppression. These findings suggest that a tumorigenic cell has lost at least two and possibly more gene functions which determine normal growth responses. The chromosomes from a normal cell can apparently correct these defects, although it is not yet clear if this is true genetic complementation or due to introduction of other genes which control cell growth or a cell's response to environmental growth regulatory stimuli. These findings led support to the view that genetic alterations are important in the process of malignant transformation and allow the development of a working hypothesis for the possible mechanisms involved. Some findings of other workers in this area also suggest that malignant cells may be producing some cell membrane proteins which are different from those of nontumorigenic cells. If this turns out to be true then it may ultimately be possible to develop immunotherapeutic procedures, i.e., to produce tumor cell specific antisera.

Animals

Glucosamine resistance in yeast. I. A preliminary genetic analysis.

Mutants of the yeast Saccaromyces cerevisiae which can grow on glycerol medium in the presence of 0.05% D (+) glucosamine have been isolated. Genetic analysis of 13 of these glucosamine resistant (GR) mutants demonstrated two modes of inheritance. One group of mutants (GR 5, 6, 7, 8, 9 and 10) gave results characteristic of non-Mendelian inheritance and it is suggested that these mutants represent one or more new mitochondial loci. Four of the remaining mutants showed clear-cut Mendelian inheritance. These mutants fell into two complementation groups and subsequent mapping experiments demonstrated that two independent loci, gay 1 and gay 2, unlinked to each other or to the centromeres of chromosomes I, II, IV, VIII or IX, were responsible for conferring glucosamine resistance in these mutants.

Chromosome Mapping

Genetic analysis of Escherichia coli O111:B4, a strain of medical and biochemical interest.

Procedures have been worked out which allow, for the first time, the genetic analysis of Escherichia coli O111:K58:H2 (O111:B4). The approximate map position of mutant loci was determined by mating with 15 Hfr strains of E. coli K-12. In addition, P1 transduction procedures were used for establishing relative gene order and linkage for any region of the E. coli O111:B4 chromosome. To obtain these, it was necessary to select for a rare P1 lysogen since E. coli O111:B4 is resistant to phage P1. Finally, genetic homology between E. coli strains K-12 and O111:B4 is suggested since they can form stable haploid hybrids, and several loci have similar map positions in the two strains.

Chromosome Mapping

[Clinical, pathologica and genetic analysis of 53 cases of broncho-pulmonary cancer, still surviving after 5 years (author's transl)].

The authors take up again the clinical, pathological and genetic analysis of 53 bronchial cancers with a survival exceeding 5 years. The operation samples were reexamined; a H.L.A. grouping was done in every cases. On the whole, it concerned patients under 60 in good general condition; the extension of their lesions only required a limited exeresis (lobectomy). The epidermoid form predominates, the lymph node invasion is rare. Seventy four per cent of the patients carry at least one of the following antigens: W 19, A 10, B 5, BW 35. But the study did not prove the existence of a genetic factor conditioning the survival.

Bronchial Neoplasms

Genetic analysis of mitochondrial biogenesis and function in Saccharomyces cerevisiae.

Different mitochondrial mutants have been isolated that affect mitochondrial ribosome function. These mutants were used to establish most of the known methods and principles of mitochondrial genetics in yeast. Another class of mitochondrial mutants have been shown to affect mitochondrial ATPase and, more specifically, the "membrane factor" of mitochondrial ATPase. These mutants might be very useful in studying the energy-conserving function, and the interaction between the hydrophobic and hydrophylic parts, of the ATPase complex. New types of mitochondrial point mutations, concerning cytochrome a-a3 or b, will soon open up new fields of investigation. The biochemical and genetic analysis of numerous mutants belonging to that category and recently obtained [31] is being currently pursued in Tzagoloff's and Slonimski's laboratories.

Adenosine Triphosphatases

Mutations affecting cell division in Tetrahymena pyriformis. I. Selection and genetic analysis.

Fourteen nitrosoguanidine-induced mutations that bring about temperature-sensitive morphological abnormalities resulting from a specific effect on cell division have been isolated as heterozygous phenotypic assortants in Tetrahymena pyriformis syngen 1. Genetic analysis revealed all to be single-gene recessives. Detailed analysis of the kinetics of assortment for one of the mutated alleles revealed a rate (0.0104 pure lines per fission) consistent with that previously observed at other loci in this organism. The mutations fall into six complementation groups (mo1, mo2, mo3, mo6, mo8, and mo12). Homozygotes of mo2 are unconditionally expresed, while all alleles of mo1, mo6, mo8, and mo12 are heat sensitive for division arrest. At the mo3 locus two alleles are heat senstivie, one is primarily cold sensitive, while two are sensitive to both heat and cold. Two out of three combinations of different mo3 alleles show conventional Mendelian segregation of conditions of expression. Different alleles of mo1, mo3, mo8, and mo12 also manifest differences in penetrance at the restrictive temperature. Despite these differences involving expression, the abnormal phenotypes themselves are locus-specific and distinctive; in the one case (mo1a and mo1b) in which two alleles manifest somewhat different phenotypes, the F1 between them is intermediate. One additional recessive mutation (fat1) brings about a nonconditional lengthening of the cell cycle, with some arrest of cell division at the restrictive temperature. These findings demonstrate that selection of heterozygotes undergoing phenotypic assortment can be an effective method for obtaining substantial numbers of a desired class of temperature-sensitive mutations in T. pyriformis.

Animals

Genetic analysis of multiple drug cross resistance in Saccharomyces cerevisiae: a nuclear-mitochondrial gene interaction.

A mutant of the yeast Saccharomyces cerevisiae, cross resistant to several antibiotics, was isolated in our laboratory and subjected to genetic analysis. Tetrad analysis of diploids obtained from crosses between the resistant mutant and a sensitive wild-type strain suggest that the multiple resistance to the five agents, oligomycin (OLI), rhodamine 6G (RHG), tetracycline (TCN), chloramphenicol (CAP) and cycloheximide (CHX) is determined by a single nuclear gene, ant1, and requires several cytoplasmic genes for expression of resistance to oligomycin, rhodamine 6G and tetracycline. --Vegetatively growing diploid clones derived from the cross ant1 [RHO+] X +[RHO+] show mitotic segregation of two phenotypic classes for the drugs OLI, RHG TCN. Diploids derived from the two reciprocal crosses, ant1 [RHO+] X +[RHO-] and ant1 [RHO-] X +[RHO+], fail to exhibit mitotic segregation. These results are consistent with our hypothesis concerning the involvement of cytoplasmic loci. They suggest, in addition, that these loci are associated with mitochondrial DNA (mtDNA). --Evidence for this association is provided by the demonstration of genetic linkage between the cytoplasmic loci involved in the interaction, RHG-1, TCN-1 and OLI-5, and two well-characterized mitochondrial loci, ERY and CAP. --We have mapped the nuclear ant1 locus 3.3 cM from the centromere-linked gene, leu1, on the same side of the centromere of chromosome VII as leu1. --In the light of these findings, we discuss the claims made by several authors of the episomal nature of mutations similar to the one described here, as well as of the possible involvement of yeast 2 mu DNA in such mutations.

Chloramphenicol

Genetic analysis of mammary tumor induction and expression of mammary tumor virus antigen in hormone-treated ovariectomized GR mice.

Early stages of mammary tumors (EMT) were induced with a combined treatment of progesterone (P) and estrone (E) in ovariectomized adult GRS/A (GR) mice, a strain of European origin and with a high incidence of mammary cancer. The mammary tumors were comparable to the pregnancy-dependent tumors of breeding females of this strain. The hormone treatment did not lead to EMT in a variety of other strains and only occasionally in the RIII an C3H strains. Treatment with P or E alone di not lead to EMT in GR mice, but treatment with the steroid compound 17 alpha-ethynyl-19-nortestosterone (ANT) did mimic the combined effe(t of P and E. Since EMT could be induced by ANT in all ovariectomized adult GR mice within 3 weeks, this tumor-induction method was suitable for analysis of the gene responsible for palpable, pregnancy-dependent mammary tumors of this strain. Another argument for the usefulness of this test for genetic analysis was the fact that, though mouse mammary tumor virus (MuMTV) of the GR strain was introduced into BALB/c and tmas mice by foster-nursing, ANT treatment did not lead to EMT. First and second backcross analyses showed that one gene was responsible for EMT induction. There was a strong (orrelation between the presence of EMT and MuMTV antigens in the mammary glands and milk of several first backcross populations between GR and other strains such as C57BL, BALB/c, DBAf, and C3Hf. This suggested that the expression of MuMTV antigens was also controlled by the EMT gene. Two types of resistance phenomena were observed. Neither type could prevent EMT after hormone treatment; however, they could delay EMT development. One resistance factor for EMT induction was noticeable and dominant in reciprocal hybrids of the GR and DBAf strains, whereas another resistance factor was detected in the backcross population only [i.e., in the C57BL X (C57BL X Gr) ba(kcross] and not in hybrids; therefore, this factor was recessive. Until now, linkage experiments with 18 markers to locate the gene for EMT induction in the map of the mouse were unsuccessful.

Animals

Genetic analysis of copper resistance in Paramecium aurelia syngen 4.

Measurement of the median tolerance limit to cupric ion of 28 wild stocks of Paramecium aurelia syngen 4 revealed a phenotypic polymorphism: two stocks showed a much greater resistance than the others. Genetic analysis showed the resistant phenotype was produced by a recessive allele, cur, identical in both resistant wild stocks. No modification of the phenotypic expression of this allele could be detected after backcrossing into different genetic backgrounds. The results are interpreted to support the importance of mutational adaptation in this inbreeding species. Possible patterns of internal genetic organization of species which rely on mutation for adaptation are discussed.

Animals

Genetic analysis of radiation-sensitive mutations in the slime mould Dictyostelium discoideum.

The linkage of two mutations leading to increased sensitivity to ultraviolet light and 60Co gamma rays was determined in the slime mould Dictyostelium discoideum using a genetic analysis based on the parasexual cycle. Diploids were selected from a mixture of radiation-sensitive, temperature-resistant and radiation-resistant, temperature-sensitive haploids on the basis of simultaneous radiation and temperature resistance. Analysis of drug-resistant haploid segregants of the heterozygous diploids indicated that one of the radiation-sensitive mutations, radA20, was linked to linkage group I whereas the other, radB13, was linked to the recently defined linkage group VI.

Cobalt Radioisotopes

[Genetic analysis of open-field behavior in mice (author's transl)].

505 mice of BB and C 57 BL/6 as parental strains, as well as derived F 1, F 2 and backcrosses were tested for spontaneous motor activities and eliminations in 4 different apparatus. A component being highly associated expecially with open-field measures was obtained from the principal component analysis. This suggests that an individual score on this composite variable represents a certain unique open-field behavioral pattern. Relatively low heritabilities in broad sense (coefficient of genetic determination) were given by classic genetic analysis, indicating the substantially great effects of the environmental factors of this behavioral character. Further, albino mice in BB, F 2 and B X B showed a very inactive open-field behavioral pattern than pigmented mice.

Animals

Isolation and genetic analysis of mutant strains of Chlamydomonas reinhardi defective in gametic differentiation.

Impotent mutant strains of Chlamydomonas reinhardi, mating-type (mt) plus, are described that have normal growth and motility but fail to differentiate into normal gametes. Procedures for their isolation and their genetic analysis are described. Five of the imp strains (imp-2, imp-5, imp-l, imp-7, and imp-8) exhibit no flagellar agglutination when mixed with mt- or mt+ gametes and the mutations are shown to be unlinked to the mt locus (with the possible exception of imp-7). Two of the strains (imp-3 and imp-4) carry leaky mutations that affect cell fusion; neither mutation is found by tetrad analysis to be linked to mt or to the other. Cells of the imp-1 strain agglutinate well with mt- gametes and active agglutination continues for up to 48 hours, but cell fusion occurs only very rarely. Analysis of these rare zygotes indicates that imp-1 is closely linked to the mt+ locus, and fine-structural studies reveal that imp-1 gametes produce a mutant mating structure involved in zygotic cell fusion. The development of sexuality in C. reinhardi therefore appears amenable to genetic dissection.

Acetates

Genetic analysis of mutations affecting ribonuclease II in Escherichia coli.

Exonuclease activity in an Escherichia coli K12 mutant S296 is less than 1% of that in the wild type strain (Nikolaev et al., 1976). Another mutant N464 has thermolabile ribonuclease II (Castles and Singer, 1968; Kuwano et al., 1969). Genetic analysis of these mutants by Hfr conjugation and P1 transduction indicates that the structural gene (rnb) for ribonuclease II is located near the pyrF gene (28 min on the E. coli genetic map of Bachmann, Low and Taylor (1976)), and the most probable gene order is tyrT-trp-pyrF-rnb.

Chromosome Mapping

A genetic analysis of aggressive behavior in two strains of mice.

Examination of BALB/cJ and A/J mouse strains revealed marked differences in their levels of isolation-induced aggression. Using the dangler paradigm, we found that BALB/cJ males were uniformly aggressive, while A/J males showed no tendency to attack. Genetic analysis showed that the expression of aggressive behavior in the F1, F2, and backcross generations was consistent with the transmission of high aggressivity as a single, autosomal recessive trait. Although the data are consistent with a major-locus effect, more complex polygenic modes of inheritance have not been excluded.

Aggression

Behavior-genetic analysis of Phormia regina: conditioning, reliable individual differences, and selection.

Using proboscis extension (unconditioned response) to sucrose (unconditioned stimulus), individual blowflies (Phormia regina) were classically conditioned to saline and to water (conditioned stimuli) with sensitization controls, thus providing unique, independently replicated evidence both of learning in Diptera and of reliably measured individual differences. Directional and stabilizing selection have bred high and low performance lines markedly different from an unselected control line as a step in the analysis of behavior-genetic correlates. This replicates and extends previous selection analysis with improved conditioning technique. Also, some unwarranted claims of learning in Diptera are discussed.

Animals

Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium.

Cystic fibrosis is the most common autosomal disorder in the Caucasian population. Since the description of the major mutation of this disease in 1989, over 150 of additional mutations have been identified in the CFTR gene. This update summarizes the different mutations identified and reported before March 15 by members of the international Cystic Fibrosis Genetic Analysis Consortium. The report includes information on DNA sequence variations found in the gene.

Amino Acid Sequence

Parasexual genetic analysis of aggregation-deficient mutants of Dictyostelium discoideum.

One hundred and thirty-nine independent, nitrosoguanidine-induced mutants blocked early in development were isolated in two haploid strains of D. discoideum. Forty of these developmental mutants were completely aggregation-deficient on bacterial lawns (Class I mutants) and these mutants were selected for parasexual genetic analysis. By fusing the Class I mutants with developmentally-competent strains the developmental mutations in 39 of these mutants were shown to be recessive; the remaining mutation appeared to be partially dominant. Complementation analysis of the developmental mutations in the Class I strains identified 5 complementation groups. Statistical analysis of the complementation data suggests that there are approximately 40 genes in this organism which will completely block aggregation when mutated and perhaps as many as 150 genes involved in some aspect of the aggregation process. Linkage analysis of 18 Class I developmental mutations revealed that 10 of these mutations map in linkage group II at a minimum of 5 loci.

Cell Aggregation