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Results for “genetic interaction”

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At least 163 records · Page 9Linked to original sources
PubMed2005

CBLB variants in type 1 diabetes and their genetic interaction with CTLA4.

Type 1 diabetes (T1D) is a multifactorial disease with genetic and environmental components involved. Recent studies of an animal model of T1D, the Komeda diabetes-prone rat, have demonstrated that the Casitas-B-lineage lymphoma b (cblb) gene is a major susceptibility gene in the development of diabetes and other autoimmune features of this rat. As a result of the inhibitory role of Cbl-b in T cell costimulation, dysregulation of Cbl-b may also contribute to autoimmune diseases in man. Different isoforms of Cbl-b exist; we evaluated expression levels of two known transcript variants. Constitutive expression of both isoforms was demonstrated, as well as an increased expression, after cytokine exposure, of an isoform lacking exon 16, suggesting a possible role of this variant in the pathogenesis of autoimmunity. We screened coding regions of the human CBLB gene for mutations in a panel of individuals affected with several autoimmune diseases. Eight single nucleotide polymorphisms (SNPs) were detected. One SNP in exon 12 of the CBLB gene was significantly demonstrated to be associated to T1D in a large Danish T1D family material of 480 families. Evidence for common genetic factors underlying several autoimmune diseases has come from studies of cytotoxic T lymphocyte antigen 4 (CTLA4), which encodes another negatively regulatory molecule in the immune system. Gene-gene interactions probably play substantial roles in T1D susceptibility. We performed stratification of CBLB exon 12 SNP data, according to an established CTLA4 marker, CT60, and evidence for a genetic interaction between the CTLA4 and CBLB genes, involved in the same biological pathway of T cell receptor signaling, was observed.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Interaction between hormonal signaling pathways in Drosophila melanogaster as revealed by genetic interaction between methoprene-tolerant and broad-complex.

Juvenile hormone (JH) regulates insect development by a poorly understood mechanism. Application of JH agonist insecticides to Drosophila melanogaster during the ecdysone-driven onset of metamorphosis results in lethality and specific morphogenetic defects, some of which resemble those in mutants of the ecdysone-regulated Broad-Complex (BR-C). The Methoprene-tolerant (Met) bHLH-PAS gene mediates JH action, and Met mutations protect against the lethality and defects. To explore relationships among these two genes and JH, double mutants were constructed between Met alleles and alleles of each of the BR-C complementation groups: broad (br), reduced bristles on palpus (rbp), and 2Bc. Defects in viability and oogenesis were consistently more severe in rbp Met or br Met double mutants than would be expected if these genes act independently. Additionally, complementation between BR-C mutant alleles often failed when MET was absent. Patterns of BRC protein accumulation during metamorphosis revealed essentially no difference between wild-type and Met-null individuals. JH agonist treatment did not block accumulation of BRC proteins. We propose that MET and BRC interact to control transcription of one or more downstream effector genes, which can be disrupted either by mutations in Met or BR-C or by application of JH/JH agonist, which alters MET interaction with BRC.

Alleles↗
PubMed2006

Genetic interactions between the parasitoid wasp Leptopilina boulardi and its Drosophila hosts.

Coevolutionary arms races between hosts and parasites would not occur without genetic variation for traits involved in the outcome of parasitism. Genetic variations in resistance and virulence have only rarely been described in pairwise host-parasitoid interactions and have never been analysed in multi-species interactions, in contrast to well-characterized plant-pathogen interactions. This paper reports genetic variation in resistance of Drosophila yakuba to the parasitoid wasp Leptopilina boulardi. The genetic basis and geographic distribution of resistance is analysed. On the basis of these and previous findings, we demonstrate that there are different resistance patterns to the parasitoid species L. boulardi in D. melanogaster and D. yakuba, as well as different specificity levels in the parasitoid species, suggesting complex ecological interactions in the field. This first description of resistance-virulence genetic interactions between a parasitoid and its two host species provides empirical data showing that multi-species interactions may greatly influence coevolutionary processes.

Animals↗
PubMed1999

Desiccation resistance in interspecific Drosophila crosses. Genetic interactions and trait correlations.

We used crosses between two closely related Drosophila species, Drosophila serrata and D. birchii, to examine the genetic basis of desiccation resistance and correlations between resistance, physiological traits, and life-history traits. D. serrata is more resistant to desiccation than D. birchii, and this may help to explain the broader geographical range of the former species. A comparison of F2's from reciprocal crosses indicated higher resistance levels when F2's originated from D. birchii mothers compared to D. serrata mothers. However, backcrosses had a resistance level similar to that of the parental species, suggesting an interaction between X-linked effects in D. serrata that reduce resistance and autosomal effects that increase resistance. Reciprocal differences persisted in hybrid lines set up from the different reciprocal crosses and tested at later generations. Increased desiccation resistance was associated with an increased body size in two sets of hybrid lines and in half-sib groups set up from the F4's after crossing the two species, but size associations were inconsistent in the F2's. None of the crosses provided evidence for a positive association between desiccation resistance and glycogen levels, or evidence for a tradeoff between desiccation resistance and early fecundity. However, fecundity was positively correlated with body size at both the genetic and phenotypic levels. This study illustrates how interspecific crosses may provide information on genetic interactions between traits following adaptive divergence, as well as on the genetic basis of the traits.

Acclimatization↗
PubMed1996

An extragenic suppressor of prp24-1 defines genetic interaction between PRP24 and PRP21 gene products of Saccharomyces cerevisiae.

The temperature-sensitive prp24-1 mutation defines a gene product required for the first step in pre-mRNA splicing. PRP24 is probably a component of the U6 snRNP particle. We have applied genetic reversion analysis to identify proteins that interact with PRP24. Spontaneous revertants of the temperature-sensitive (ts)prp24-1 phenotype were analyzed for those that are due to extragenic suppression. We then extended our analysis to screen for suppressors that confer a distinct conditional phenotype. We have identified a temperature-sensitive extragenic suppressor, which was shown by genetic complementation analysis to be allelic to prp21-1. This suppressor, prp21-2, accumulates pre-mRNA at the non-permissive temperature, a phenotype similar to that of prp21-1. prp21-2 completely suppresses the splicing defect and restores in vivo levels of the U6 snRNA in the prp24-1 strain. Genetic analysis of the suppressor showed that prp21-2 is not a bypass suppressor of prp24-1. The suppression of prp24-1 by prp21-2 is gene specific and also allele specific with respect to both the loci. Genetic interactions with other components of the pre-spliceosome have also been studied. Our results indicate an interaction between PRP21, a component of the U2 snRNP, and PRP24, a component of the U6 snRNP. These results substantiate other data showing U2-U6 snRNA interactions.

Alleles↗
PubMed1996

Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload?

1. Dohan has proposed that schizophrenia is a genetic disposition which interacts with an overload of dietary proteins such as casein and gluten or gliadin. 2. A systematic attempt is made to see if this hypothesis is possible faced with aspects of schizophrenia that must be accounted for. 3. The authors conclusion is that it is possible, but more serious work in this field is urgently needed.

Dietary Proteins↗
PubMed1995

fs (1) Yb is required for ovary follicle cell differentiation in Drosophila melanogaster and has genetic interactions with the Notch group of neurogenic genes.

Phenotypic and genetic analyses demonstrate that fs (1) Yb activity is required in the soma for the development of a subset of ovarian follicle cells and to support later stages of egg maturation. Mutations in fs (1) Yb cause a range of ovarian phenotypes, from the improper segregation of egg chambers to abnormal dorsal appendage formation. The mutant phenotypes associated with fs (1) Yb are very similar to the ovarian aberrations produced by temperature-sensitive alleles of Notch and Delta. Possible functional or regulatory interactions between fs (1) Yb and Notch are suggested by genetic studies. A duplication of the Notch locus partially suppresses the female-sterility caused by fs (1) Yb mutations, while reducing Notch dosage makes the fs (1) Yb mutant phenotype more severe. In addition, fs (1) Yb alleles also interact with genes that are known to act with or regulate Notch activity, including Delta, daughterless, and mastermind. However, differences between the mutant ovarian phenotype of fs (1) Yb and that of Notch or Delta indicate that the genes do not have completely overlapping functions in the ovary. We propose that fs (1) Yb acts as an ovary-specific factor that determines follicle cell fate.

Alleles↗
PubMed2026

Genetic interactions between PIWI subfamily genes and hobo transposons modulate Drosophila melanogaster lifespan under chronic low-intensity irradiation.

In recent decades, there has been active research into how ionizing radiation at low doses, an inevitable factor in human activity, affects aging processes and which molecular genetic mechanisms underlie this influence. This study investigates the effects of mutations in PIWI subfamily genes (piwi and aub), which regulate transposable elements, on the lifespan of Drosophila melanogaster under conditions of genome instability induced by hobo transposons and chronic low-intensity irradiation (20 cGy). It is shown that dysfunction of piwi and aub modulates the activity of hobo transposons, increasing the frequency of their excisions/transpositions and recombinogenic activity, as confirmed by phenotypic and PCR analyses. The presence of hobo transposons in the genome elevates the spontaneous level of DNA fragmentation in ovarian cells, and chronic irradiation enhances this effect, leading to increased DNA damage in somatic and germline cells of most studied strains. Despite increased genetic instability and reduced fertility in some genotypes, the combined presence of mutations and hobo transposons paradoxically increases lifespan both under control conditions and after irradiation. Analysis of the interaction between genetic factors reveals a predominantly antagonistic, and in one case synergistic, effect on lifespan, depending on the type of mutation, the structure of the hobo transposons (full-size or defective copies), sex, and irradiation conditions. These results demonstrate the complex interplay between systems controlling transpositional activity and stress-induced processes that affect key viability parameters.

Animals↗
PubMed2006

Disruption of genetic interaction between two autosomal regions and the X chromosome causes reproductive isolation between mouse strains derived from different subspecies.

Reproductive isolation that initiates speciation is likely caused by incompatibility among multiple loci in organisms belonging to genetically diverging populations. Laboratory C57BL/6J mice, which predominantly originated from Mus musculus domesticus, and a MSM/Ms strain derived from Japanese wild mice (M. m. molossinus, genetically close to M. m. musculus) are reproductively isolated. Their F1 hybrids are fertile, but successive intercrosses result in sterility. A consomic strain, C57BL/6J-ChrX(MSM), which carries the X chromosome of MSM/Ms in the C57BL/6J background, shows male sterility, suggesting a genetic incompatibility of the MSM/Ms X chromosome and other C57BL/6J chromosome(s). In this study, we conducted genomewide linkage analysis and subsequent QTL analysis using the sperm shape anomaly that is the major cause of the sterility of the C57BL/6J-ChrX(MSM) males. These analyses successfully detected significant QTL on chromosomes 1 and 11 that interact with the X chromosome. The introduction of MSM/Ms chromosomes 1 and 11 into the C57BL/6J-ChrX(MSM) background failed to restore the sperm-head shape, but did partially restore fertility. This result suggests that this genetic interaction may play a crucial role in the reproductive isolation between the two strains. A detailed analysis of the male sterility by intracytoplasmic sperm injection and zona-free in vitro fertilization demonstrated that the C57BL/6J-ChrX(MSM) spermatozoa have a defect in penetration through the zona pellucida of eggs.

Animals↗
PubMed2005

On the theoretical and empirical framework for studying genetic interactions within and among species.

We present a quantitative genetic (QG) interpretation of the Bateson-Dobzhansky-Muller (BDM) genetic model of speciation in order to unify the theoretical framework for understanding how the genetic differentiation of populations is associated with the process of speciation. Specifically, we compare the QG theory of joint scaling with the Turelli-Orr mathematical formulation of the BDM model. By formally linking the two models, we show that a wealth of empirical methods from QG can be brought to bear on the study of the genetic architecture of hybrid phenotypes to better understand the connections, if any, between microevolution within populations and macroevolution in the origin of species. By integrating the two theories, we make additional novel predictions that enrich the opportunities for empirically testing speciation genetic theory or facets of it, such as Haldane's rule. We show that the connection between the two theories is simple and straightforward for autosomal genes but not for sex-linked genes. Differences between the two approaches highlight key conceptual issues concerning the relevance of epistasis to evolution within and among lineages and to differences in the process of speciation in hermaphrodites and in organisms with separate sexes.

Animals↗
PubMed1992

Genetic interactions in the control of septation in Schizosaccharomyces pombe.

We have used genetic and molecular techniques to investigate the interactions among genes required for the initiation and regulation of septum formation in Schizosaccharomyces pombe. Our data suggest that the products of the cdc7, cdc11, cdc14 and cdc16 genes interact. These activities may regulate the function of the cdc15 gene product. A model for the control of septation in fission yeast is presented.

Cell Division↗
PubMed2006

Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster.

Understanding the genetic architecture of complex traits requires identification of the underlying genes and characterization of gene-by-gene and genotype-by-environment interactions. Behaviors that mediate interactions between organisms and their environment are complex traits expected to be especially sensitive to environmental conditions. Previous studies on the olfactory avoidance response of Drosophila melanogaster showed that the genetic architecture of this model behavior depends on epistatic networks of pleiotropic genes. We performed a screen of 1339 co-isogenic p[GT1]-element insertion lines to identify novel genes that contribute to odor-guided behavior and identified 55 candidate genes with known p[GT1]-element insertion sites. Characterization of the expression profiles of 10 p[GT1]-element insertion lines showed that the effects of the transposon insertions are often dependent on developmental stage and that hypomorphic mutations in developmental genes can elicit profound adult behavioral deficits. We assessed epistasis among these genes by constructing all possible double heterozygotes and measuring avoidance responses under two stimulus conditions. We observed enhancer and suppressor effects among subsets of these P-element-tagged genes, and surprisingly, epistatic interactions shifted with changes in the concentration of the olfactory stimulus. Our results show that the manifestation of epistatic networks dynamically changes with alterations in the environment.

Animals↗
PubMed1985

Genetic interactions in early neurogenesis of Drosophila melanogaster.

A number of genetic loci, called neurogenic, have been found to be involved in directing the segregation of neural and epidermal lineages within the ectodermal germ layer of Drosophila melanogaster. With the aim of understanding the regulation of this developmental function we have studied interactions of the loci N, Dl and E(spl) among each other and with another locus (H), by means of increasing and decreasing the number of wild-type copies of one of these genes in the presence of mutations in another one. The results reveal functional community which exists among these neurogenic loci. E(spl) overlaps functionally with both N and Dl because genotypes involving only one copy of E(spl)+ and either an N or Dl mutation are lethal. Furthermore the normal H+ allele behaves as if it represses the activity of the 3 neurogenic loci; and, whereas E(spl) seems to be a close target of H repressing action, the influence of H upon the other two seems to be indirect.

Alleles↗
PubMed1982

Genetic interactions in induction of endogenous murine leukemia virus from low leukemic mice.

The frequency of ecotropic murine leukemia virus (MuLV) production in cells induced with halogenated pyrimidines has been investigated in several low leukemic strains of mice. Very few BALB/c or C57BL/6 (B6) induced embryo cells produce MuLV; this low frequency increases 10 to 50 fold in cells of the BALB/c x B6 F1 hybrid. Data from back-crosses of the F1 hybrid to each parent and from BALB/c x B6 recombinant inbred strains indicate that the phenotype of enhanced MuLV production results from interaction of two unlinked loci, dominant (+/+) alleles of which are carried by either parent. Genetic tests with BALB/c x B6 recombinant inbred strains confirm this two-locus model. The loci are designated Inc-1 and Inb-1 to signify their phenotypic detection by induction and the BALB/c or B6 strain of origin, respectively. Examination of hybrids of BALB/c and of B6 with other strains indicates that strains related in pedigree to BALB/c carry Inc-1, whereas those related to B6 carry Inb-1. Identification of genetic loci that specifically interact to enhance MuLV production after exposure to halogenated pyrimidines indicates the existence of mechanisms that regulate the induction or intracellular expression of endogenous MuLV.

Animals↗
PubMed2006

Genetic interaction between Lef1 and Alx4 is required for early embryonic development.

Lymphoid Enhancer Factor-1 (Lef1) facilitates the assembly of transcriptional regulatory complexes and mediates nuclear responses to Wnt signals. We determined previously that the mesenchymally restricted, paired-like homeodomain protein Aristaless-like 4 (Alx4) interacts with Lef1 and together alters promoter activity of candidate genes. In order to define their overlapping functions, mice deficient for both Lef1 and Alx4 activity (Lef1-/-/Alx4lstD/lstD) were produced. Whereas embryos lacking either Lef1 or Alx4 activity remain viable up to or after birth, early embryonic lethality results when both factors were absent. No viable Lef1-/-/Alx4lstD/lstD embryos were recovered beyond 9.5 dpc. Between E8.5 and E10, viable Lef1-/-/Alx4lstD/lstD embryos were developmentally delayed 0.5 days relative to littermates of all other genotypes. Principle among the alterations seen in Lef1-/-/Alx4lstD/lstD animals was defective vasculature in both embryonic and extra-embryonic tissues. In the yolk sac, while the vascular network is present, it were greatly diminished and large vitelline vessels were largely absent. Platelet/endothelial cell adhesion molecule (PECAM) staining revealed that the major vessels in the head of compound mutant embryos were absent, while the other vessels were finer than those seen in normal littermates. Pools of blood and pericardial effusion were also apparent in Lef1-/-/Alx4lstD/lstD animals, further indicative of a defective vasculature. These data confirm genetically the interaction between Lef1 and Alx4 and further reveal unknown, overlapping roles for these transcription factors in embryonic vasculogenesis.

Animals↗