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At least 307 records · Page 17Linked to original sources
PubMed2002

Gene-dosage-sensitive genetic interactions between inversus viscerum (iv), nodal, and activin type IIB receptor (ActRIIB) genes in asymmetrical patterning of the visceral organs along the left-right axis.

We have shown previously that mice deficient in the activin type IIB receptor (ActRIIB) exhibit right isomerism, which is characterized by mirror-image symmetrical right lungs, complex cardiac malformations, and hypoplasia of the spleen. These observations led us to hypothesize that the signaling of a TGF-beta family member by means of ActRIIB is necessary for the determination of the left-sidedness of the visceral organs. To test this hypothesis, we examined laterality defects in mice carrying mutations in both ActRIIB and inversus viscerum (iv) genes, because iv(-/-) mice display a spectrum of laterality defects, including situs inversus, right isomerism, and left isomerism. We found that all mice homozygous for both iv and ActRIIB mutations displayed the right isomerism. The phenotype of right isomerism in the double mutants was also more severe than that in ActRIIB(-/-) mice as shown by persistent left inferior vena cava, right atrial isomerism, and hypoplasia of spleen. Interestingly, the incidence of right isomerism also increased significantly in iv(-/-);ActRIIB(+/-) and iv(+/-);ActRIIB(-/-) mice compared with homozygous mice carrying either of single gene mutations. A mechanism of the genetic modulation between ActRIIB and iv genes may be that iv modulates the asymmetric expression of a TGF-beta family member that signals through activin type II receptors, ActRIIA and ActRIIB, to specify the "left-sidedness." Nodal is the most likely candidate. We show here that the penetrance and severity of the right isomerism is significantly elevated in nodal(+/-); ActRIIB(-/-) mice, compared with ActRIIB(-/-) mice. Furthermore, the chimeric mice derived from nodal(-/-) ES cells displayed right isomerism, indistinguishable from that in (iv(-/-);ActRIIB(-/-)) mice. We propose that iv functions to establish asymmetric expression of nodal in a gene-dosage-sensitive manner and that nodal signals through the activin type II receptors to specify the left-sidedness by means of a threshold mechanism.

Activin Receptors, Type II↗
PubMed1981

Genetic interactions among viruses of the Bunyamwera complex.

Seventy-seven temperature-sensitive (ts) mutants belonging to three antigenically distinct and geographically isolated members of the Bunyamwera complex--Batai virus, Bunyamwera virus, and Maguari virus--have been isolated after 5-fluorouracil treatment. High-frequency recombination was observed, and the mutants of each virus were classified into two groups, which were shown to be equivalent by heterologous recombination experiments. In most combinations heterologous recombination was less efficient than homologous recombination, but all crosses of group I and II mutants yielded viable recombinants. Recombination was an early event. Analysis by polyacrylamide gel electrophoresis of the proteins of the wild-type viruses and recombinant clones obtained from the six possible heterologous combinations of group I and II mutants indicated that recombination occurred by reassortment of genome subunits. Group I appeared to correspond to the genome subunit coding for the N protein, and group II corresponded to the G1/G2 determinant. The G1 (or G2 or both) protein was associated with neutralization specificity and plaque diameter, and the N protein was associated with plaque opacity. Complementation was observed between two nonrecombining mutants of Maguari virus belonging to group I, which may indicate that the N genome subunit codes for an additional protein. There appeared to be no genetic barrier to exchange of genetic material between Batai, Bunyamwera, and Maguari viruses in vitro, and it is concluded that the Bunyamwera complex is potentially a single gene pool if geographical and ecological constraints are discounted.

Bunyamwera virus↗
PubMed2004

Genetic interactions between hepatitis C virus replicons.

To investigate interactions between hepatitis C virus (HCV) RNA replication complexes, a system was developed to simultaneously select different HCV subgenomic replicons within the same cell. Transcomplementation of defective replicons was not observed, suggesting an isolated and independent nature of the HCV RNA replication complex. In contrast, a high level of competition between replicons was observed, such that the presence and increased fitness of one replicon reduced the capacity of a second one to stably replicate. These results suggest that at least one factor in Huh7 cells required for HCV RNA replication is limiting and saturable.

Genetic Complementation Test↗
PubMed2004

Schizosaccharomyces pombe rsm1 genetically interacts with spmex67, which is involved in mRNA export.

We have previously isolated three synthetic lethal mutants from Schizosaccharomyces pombe in order to identify mutations in the genes that are functionally linked to spmex67 with respect to mRNA export. A novel rsm1 gene was isolated by complementation of the growth defect in one of the synthetic lethal mutants, SLMexl. The rsm1 gene contains no introns and encodes a 296 amino-acid-long protein with the RING finger domain, a C3HC4 in the N-terminal half. The deltarsm1 null mutant is viable, but it showed a slight poly(A)+ RNA accumulation in the nucleus. Also, the combination of deltarsm1 and deltaspmex67 mutations confers synthetic lethality that is accompanied by the severe poly(A)+ RNA export defect. These results suggest that rsm1 is involved in mRNA export from the nucleus.

Biological Transport↗
PubMed1999

The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription.

The trithorax group gene brahma (brm) encodes the ATPase subunit of a chromatin-remodeling complex involved in homeotic gene regulation. We report here that brm interacts with another trithorax group gene, osa, to regulate the expression of the Antennapedia P2 promoter. Regulation of Antennapedia by BRM and OSA proteins requires sequences 5' to the P2 promoter. Loss of maternal osa function causes severe segmentation defects, indicating that the function of osa is not limited to homeotic gene regulation. The OSA protein contains an ARID domain, a DNA-binding domain also present in the yeast SWI1 and Drosophila DRI proteins. We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes.

Animals↗
PubMed1999

Suppressor analysis of the Saccharomyces cerevisiae gene REC104 reveals a genetic interaction with REC102.

REC104 is a gene required for the initiation of meiotic recombination in Saccharomyces cerevisiae. To better understand the role of REC104 in meiosis, we used an in vitro mutagenesis technique to create a set of temperature-conditional mutations in REC104 and used one ts allele (rec104-8) in a screen for high-copy suppressors. An increased dosage of the early exchange gene REC102 was found to suppress the conditional recombinational reduction in rec104-8 as well as in several other conditional rec104 alleles. However, no suppression was observed for a null allele of REC104, indicating that the suppression by REC102 is not "bypass" suppression. Overexpression of the early meiotic genes REC114, RAD50, HOP1, and RED1 fails to suppress any of the rec104 conditional alleles, indicating that the suppression might be specific to REC102.

Alleles↗
PubMed2025

Genetic interactions and natural variation underlying S-RNase-independent unilateral incompatibility in Solanum.

Pistils of self-incompatible (SI) species/populations typically reject pollen of related self-compatible (SC) species/populations, but not vice versa, a pattern known as unilateral incompatibility (UI). UI is complex and includes both S-RNase-dependent and S-RNase-independent mechanisms. Pistils of Solanum pennellii LA0716 (SC, no S-RNase) reject pollen of cultivated tomato, Solanum lycopersicum (SC); UI in this system involves the expression of ornithine decarboxylase2 (ODC2) and HT-A/-B genes in the pistil, and farnesyl pyrophosphate synthase2 (FPS2), ui6.2, and ui12.2 in pollen. We show that IL12-3 (HT-A/-B) × IL3-3 (ODC2) double introgression lines reject S. lycopersicum pollen, while odc2 or ht-a mutants do not, demonstrating that ODC2 and HT-A are required for UI. Transmission ratio distortion in favor of pennellii alleles was observed in interspecific F2 S. lycopersicum × S. pennellii near ui6.2 and ui12.2, and in F2 IL12-3 × IL3-3 near ui12.2. Equivalent populations made with odc2 mutants segregate in Mendelian ratios, while ht-a mutants have little effect, indicating ui6.2 and ui12.2 interact primarily with ODC2. Pollen from fps2 mutants in S. pennellii LA0716 are incompatible on pistils of all tested S. pennellii and some Solanum habrochaites accessions, but compatible with all other tomato clade species, suggesting ODC2-dependent UI evolved in a common ancestor to S. pennellii and S. habrochaites. Within S. habrochaites, fps2 pollen rejection was observed mainly in SI or mixed mating populations, suggesting an association with outcrossing. Triple mutants of S. pennellii and S. habrochaites lacking functional ODC2, HT-A/-B, and S-RNase are cross-compatible as female parents with S. lycopersicum, allowing transfer of their cytoplasmic genomes into cultivated tomato.

Solanum↗
PubMed2006

Genetic interactions in the control of flowering time and reproductive structure development in tomato (Solanum lycopersicum).

Different tomato (Solanum lycopersicum) mutants, affected in flowering time, reproductive structure or plant architecture, were crossed to produce double mutants in order to investigate gene interactions in flowering regulation in this autonomous species with a sympodial growth habit. The compound inflorescence: uniflora, uniflora: self pruning, uniflora: blind, and jointless: uniflora double mutants all produced solitary flowers like their uniflora parent, instead of inflorescences. All double mutants were late flowering. uniflora: blind and uniflora: self pruning had flowering times intermediate between those of their two parents. jointless: uniflora and compound inflorescence: uniflora flowered later than uniflora, the mutant with the most delayed flowering. All double mutants developed strong lateral shoots at node levels approximately corresponding to the level at which their parent cultivars initiated their first reproductive structure, which is a typical trait of uniflora. These results suggest that the UNIFLORA gene acts upstream of the other investigated genes in controlling flowering in tomato, and that floral transition of the primary shoot and floral transition of sympodial segments are regulated differently.

Crosses, Genetic↗
PubMed2006

Genetic interaction between expanded murine Hdh alleles and p53 reveal deleterious effects of p53 on Huntington's disease pathogenesis.

Huntingtin, the protein product of the Huntington's disease (HD) gene, is known to interact with the tumor suppressor p53. It has recently been shown that activation of p53 upregulates the level of huntingtin, both in vitro and in vivo, whereas p53 deficiency in HD-transgenic flies and mice has been found to be beneficial. To explore further the involvement of p53 in HD pathogenesis, we generated mice homozygous for a mutant allele of Hdh (HdhQ140) and with zero, one, or two functional alleles of p53. p53 deficiency resulted in a reduction of mutant huntingtin expression in brain and testis, an increase in proenkephalin mRNA expression and a significant increase in nuclear aggregate formation in the striatum. Because aggregation of mutant huntingtin is suggested to be a protective mechanism, both the increase in aggregate load and the restoration of proenkephalin expression suggest a functional rescue of at least several aspects of the HD phenotype by a deficiency in p53.

Alleles↗
PubMed1996

Genetic interactions between REG1/HEX2 and GLC7, the gene encoding the protein phosphatase type 1 catalytic subunit in Saccharomyces cerevisiae.

Mutations in GLC7, the gene encoding the type 1 protein phosphatase catalytic subunit, cause a variety of abberrant phenotypes in yeast, such as impaired glycogen synthesis and relief of glucose repression of the expression of some genes. Loss of function of the REG1/HEX2 gene, necessary for glucose repression of several genes, was found to suppress the glycogen-deficient phenotype of the glc7-1 allele. Deletion of REG1 in a wild-type background led to overaccumulation of glycogen as well as slow growth and an enlarged cell size. However, loss of REG1 did not suppress other phenotypes associated with GLC7 mutations, such as inability to sporulate or, in cells bearing the glc7Y-170 allele, lack of growth at 14 degrees. The effect of REG1 deletion on glycogen accumulation is not simply due to derepression of glucose-repressed genes, although it does require the presence of SNF1, which encodes a protein kinase essential for expression of glucose-repressed genes and for glycogen accumulation. We propose that REG1 has a role in controlling glycogen accumulation.

Base Sequence↗
PubMed2001

Mapping by genetic interaction: high-resolution congenic mapping of the type 1 diabetes loci Idd10 and Idd18 in the NOD mouse.

As many of the linked chromosome regions that predispose to type 1 diabetes in the NOD mouse have been dissected, it has become apparent that the initially observed effect is in fact attributable to several loci. One such cluster of loci on distal chromosome 3, originally described as Idd10, is now known to comprise three separate loci, Idd10, Idd17, and Idd18. Although these loci have a significant combined effect on diabetes development, their individual effects are barely detectable when diabetes is used as a read-out, which makes fine-mapping them by use of a conventional congenic approach impractical. In this study, we demonstrate that it is possible to map loci, with modest effects, to regions small enough for systematic gene identification by capitalizing on the fact that the combined loci provide more profound, measurable protection. We have mapped the Idd10 and Idd18 loci to 1.3- and 2.0-cM intervals, respectively, by holding the Idd3 allele constant. In addition, we have excluded Csf1 and Nras as candidates for both loci.

Animals↗
PubMed1999

Genetic interactions of the Arabidopsis flowering time gene FCA, with genes regulating floral initiation.

The genes controlling the timing of the transition from vegetative to reproductive growth are likely candidates for regulators of genes initiating floral development. We have investigated the interaction of one particular gene controlling flowering time, FCA, with the meristem identity-genes TERMINAL FLOWER 1 (TFL1), APETALA 1 (AP1) and LEAFY (LFY) and the floral repression gene EMBRYONIC FLOWER 1 (EMF1). Double mutant combinations were generated and the phenotypes characterized. The influence of strong and intermediate fca mutant alleles on the phenotype conferred by a 35S-LFY transgene was also analysed. The results support a model where FCA function promotes flowering in multiple pathways, one leading to activation of LFY and AP1, and another acting in parallel with LFY and AP1. Only the latter pathway is predicted to be non-functional in the intermediate fca-4 allele. The results are also consistent with AP1 and TFL1 negatively regulating FCA function. Combination of Columbia fca and emf1 mutant alleles confirmed that FCA is required for the early flowering of emf1. EMF1 and FCA are therefore likely to operate in different floral pathways.

Alleles↗
PubMed1988

Genetic interactions of modifier genes and modifiable alleles in Drosophila melanogaster.

We have examined the effects of mutations in the six allele-specific modifier genes su(Hw), e(we), su(f), su(s), su(wa), and su(pr) on the expression of 18 modifiable alleles, situated at 11 loci. Ten of the modifiable alleles are associated with insertions of the gypsy retrotransposon and the others include alleles associated with insertions of copia and 412. We tested or retested 90 of the 108 possible combinations and examined the expression of modifiable alleles in flies mutant for pairs of modifier genes in various heterozygous and homozygous configurations. Our principal findings are: (1) a screen of 40,000 mutagenized X chromosomes yielded three new mutations in known modifier genes, but revealed no new modifier genes; (2) the modification effects of different mutations in a given modifier gene were qualitatively similar; (3) each of the six modifiers suppressed some modifiable alleles, enhanced others, and had no noticeable effect on still others; (4) the modifier genes could be placed in four classes, according to their effects on the gypsy-insertion alleles; and (5) the effects of mutations in different modifier genes combined additively. Implications of these results for models of modifier gene action are discussed.

Alleles↗
PubMed2006

The role of AtMUS81 in DNA repair and its genetic interaction with the helicase AtRecQ4A.

The endonuclease MUS81 has been shown in a variety of organisms to be involved in DNA repair in mitotic and meiotic cells. Homologues of the MUS81 gene exist in the genomes of all eukaryotes, pointing to a conserved role of the protein. However, the biological role of MUS81 varies between different eukaryotes. For example, while loss of the gene results in strongly impaired fertility in Saccharomyces cerevisiae and nearly complete sterility in Schizosaccharomyces pombe, it is not essential for meiosis in mammals. We identified a functional homologue (AtMUS81/At4g30870) in the genome of Arabidopsis thaliana and isolated a full-length cDNA of this gene. Analysing two independent T-DNA insertion lines of AtMUS81, we found that they are sensitive to the mutagens MMS and MMC. Both mutants have a deficiency in homologous recombination in somatic cells but only after induction by genotoxic stress. In contrast to yeast, no meiotic defect of AtMUS81 mutants was detectable and the mutants are viable. Crosses with a hyperrecombinogenic mutant of the AtRecQ4A helicase resulted in synthetic lethality in the double mutant. Thus, the nuclease AtMUS81 and the helicase AtRecQ4A seem to be involved in two alternative pathways of resolution of replicative DNA structures in somatic cells.

Amino Acid Sequence↗
PubMed2004

Genetic interactions among regulators of septin organization.

Septins form a cortical scaffold at the yeast mother-bud neck that restricts the diffusion of cortical proteins between the mother and bud and serves as a signaling center that is important for governing various cell functions. After cell cycle commitment in late G(1), septins are assembled into a narrow ring at the future bud site, which spreads to form a mature septin hourglass immediately after bud emergence. Although several septin regulators have been identified, it is unclear how they cooperate to assemble the septin scaffold. We have examined septin localization in isogenic strains containing single or multiple mutations in eight septin organization genes (CDC42, RGA1, RGA2, BEM3, CLA4, GIN4, NAP1, and ELM1). Our results suggest that these regulators act largely in parallel to promote either the initial assembly of the septin ring (CDC42, RGA1, RGA2, BEM3, and CLA4) or the conversion of the ring to a stable hourglass structure at the neck (GIN4, NAP1, and ELM1). Aberrant septin localization patterns in mutant strains could be divided into apparently discrete categories, but individual strains displayed heterogeneous defects, and there was no clear-cut correspondence between the specific mutations and specific categories of defect. These findings suggest that when they are deprived of their normal regulators, septin scaffolds collapse into a limited repertoire of aberrant states in which the nature of the mutant regulators influences the probability of a given aberrant state.

Cell Cycle↗
PubMed2004

Genetic interaction of an origin recognition complex subunit and the Polycomb group gene MEDEA during seed development.

The eukaryotic origin recognition complex (ORC) is made up of six subunits and functions in nuclear DNA replication, chromatin structure, and gene silencing in both fungi and metazoans. We demonstrate that disruption of a plant ORC subunit homolog, AtORC2 of Arabidopsis (Arabidopsis thaliana), causes a zygotic lethal mutant phenotype (orc2). Seeds of orc2 abort early, typically producing embryos with up to eight cells. Nuclear division in the endosperm is arrested at an earlier developmental stage: only approximately four nuclei are detected in orc2 endosperm. The endosperm nuclei in orc2 are dramatically enlarged, a phenotype that is most similar to class B titan mutants, which include mutants in structural maintenance of chromosomes (SMC) cohesins. The highest levels of ORC2 gene expression were found in preglobular embryos, coinciding with the stage at which homozygous orc2 mutant seeds arrest. The homologs of the other five Arabidopsis ORC subunits are also expressed at this developmental stage. The orc2 mutant phenotype is partly suppressed by a mutation in the Polycomb group gene MEDEA. In double mutants between orc2 and medea (mea), orc2 homozygotes arrest later with a phenotype intermediate between those of mea and orc2 single mutants. Either alterations in chromatin structure or the release of cell cycle checkpoints by the mea mutation may allow more cell and nuclear divisions to occur in orc2 homozygous seeds.

Arabidopsis↗
PubMed1997

Genetic interactions in zebrafish midline development.

Mutational analyses have shown that the genes no tail (ntl, Brachyury homolog), floating head (flh, a Not homeobox gene), and cyclops (cyc) play direct and essential roles in the development of midline structures in the zebrafish. In both ntl and flh mutants a notochord does not develop, and in cyc mutants the floor plate is nearly entirely missing. We made double mutants to learn how these genes might interact. Midline development is disrupted to a greater extent in cyc;flh double mutants than in either cyc or flh single mutants; their effects appear additive. Both the notochord and floor plate are completely lacking, and other phenotypic disturbances suggest that midline signaling functions are severely reduced. On the other hand, trunk midline defects in flh;ntl double mutants are not additive, but are most often similar to those in ntl single mutants. This finding reveals that loss of ntl function can suppress phenotypic defects due to mutation at flh, and we interpret it to mean that the wild-type allele of ntl (ntl+) functions upstream to flh in a regulatory hierarchy. Loss of function of ntl also strongly suppresses the floor plate deficiency in cyc mutants, for we found trunk floor plate to be present in cyc;ntl double mutants. From these findings we propose that ntl+ plays an early role in cell fate choice at the dorsal midline, mediated by the Ntl protein acting to antagonize floor plate development as well as to promote notochord development.

Animals↗
PubMed2001

The Schizosaccharomyces pombe spo3+ gene is required for assembly of the forespore membrane and genetically interacts with psy1(+)-encoding syntaxin-like protein.

Formation of the forespore membrane, which becomes the plasma membrane of spores, is an intriguing step in the sporulation of the fission yeast Schizosaccharomyces pombe. Here we report two novel proteins that localize to the forespore membrane. spo3(+) encodes a potential membrane protein, which was expressed only during sporulation. Green fluorescent protein (GFP) fusion revealed that Spo3 localized to the forespore membrane. The spo3 disruptant was viable and executed meiotic nuclear divisions as efficiently as the wild type but did not form spores. One of the spo3 alleles, spo3-KC51, was dose-dependently suppressed by psy1(+), which encodes a protein similar to mammalian syntaxin-1A, a component of the plasma membrane docking/fusion complex. psy1(+) was essential for vegetative growth, and its transcription was enhanced during sporulation. As expected, Psy1 localized to the plasma membrane during vegetative growth. Interestingly, Psy1 on the plasma membrane disappeared immediately after first meiotic division and relocalized to the forespore membrane as the second division initiated. In the spo3 null mutant, the forespore membrane was initiated but failed to develop a normal morphology. Electron microscopy revealed that membrane vesicles were accumulated in the cytoplasm of immature spo3Delta asci. These results suggest that Spo3 is a key component of the forespore membrane and is essential for its assembly acting in collaboration with the syntaxin-like protein.

Amino Acid Sequence↗