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Spontaneous Mutation (spontaneous + mutation)

Distribution by Scientific Domains

Life Sciences	80%
Medical Sciences	19%

Distribution within Life Sciences

Neuroscience	17%
Genetics	11%

Selected Abstracts

THE CONTRIBUTION OF SPONTANEOUS MUTATION TO VARIATION IN ENVIRONMENTAL RESPONSES OF ARABIDOPSIS THALIANA: RESPONSES TO LIGHT

EVOLUTION, Issue 2 2005
Christina M. Kavanaugh
Abstract It has been hypothesized that new, spontaneous mutations tend to reduce fitness more severely in more stressful environments. To address this hypothesis, we grew plants representing 20 Arabidopsis thaliana mutationaccumulation (M-A) lines, advanced to generation 17, and their progenitor, in differing light conditions. The experiment was conducted in a greenhouse, and two treatments were used: full sun and shade, in which influx of red light was reduced relative to far-red. The shade treatment was considered the more stressful because mean absolute fitness was lower in that treatment, though not significantly so. Plants from generation 17 of M-A developed significantly faster than those from generation 0 in both treatments. A significant interaction between generation and treatment revealed that, counter to the hypothesis, M-A lines tended to have higher fitness on average relative to the progenitor in the shaded conditions, whereas, in full sun, the two generations were similar in fitness. A secondary objective of this experiment was to characterize the contribution of new mutations to genotype x environment interaction. We did not, however, detect a significant interaction between M-A line and treatment. Plots of the line-specific enviromental responses indicate no tendency of new mutations to contribute to fitness trade-offs between environments. They also do not support a model of conditionally deleterious mutation, in which a mutatn reduces fitness only in a particular environment. These results suggest that interactions between genotype and light environment previously documented for A. thaliana are not explicable primarily as a consequence of steady input of spontaneous mutations having environment-specific effects. [source]

THE FITNESS EFFECTS OF SPONTANEOUS MUTATIONS IN CAENORHABDITIS ELEGANS

EVOLUTION, Issue 4 2000
Larissa L. Vassilieva
Abstract. Spontaneous mutation to mildly deleterious alleles has emerged as a potentially unifying component of a variety of observations in evolutionary genetics and molecular evolution. However, the biological significance of hypotheses based on mildly deleterious mutation depends critically on the rate at which new mutations arise and on their average effects. A long-term mutation-accumulation experiment with replicate lines of the nematode Caenorhabditis elegans maintained by single-progeny descent indicates that recurrent spontaneous mutation causes approximately 0.1% decline in fitness per generation, which is about an order of magnitude less than that suggested by previous studies with Drosophila. Two rather different approaches, Bateman-Mukai and maximum likelihood, suggest that this observation, along with the observed rate of increase in the variance of fitness among lines, is consistent with a genomic deleterious mutation rate for fitness of approximately 0.03 per generation and with an average homozygous effect of approximately 12%. The distribution of mutational effects for fitness appears to have a relatively low coefficient of variation, being no more extreme than expected for a negative exponential, and for one composite fitness measure (total progeny production) approaches constancy of effects. These results are derived from assays in a benign environment. At stressful temperatures, estimates of the genomic deleterious mutation rate (for genes expressed at such temperatures) is sixfold lower, whereas those for the average homozygous effect is approximately eightfold higher. Our results are reasonably compatible with existing estimates for flies, when one considers the differences between these species in the number of germ-line cell divisions per generation and the magnitude of transposable element activity. [source]

Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland

DEVELOPMENTAL DYNAMICS, Issue 4 2003
Paul C. Marker
Abstract The seminal vesicles and prostate gland are anatomically adjacent male sex-accessory glands. Although they arise from different embryonic precursor structures and express distinct sets of secretory proteins, these organs share common features in their developmental biology. A key shared developmental feature is the elaboration of complex secretory epithelia with tremendous surface area from simple precursor structures with juxtaposed epithelial and mesenchymal cells. In this study, new insight into the nature of the biological processes that underlie glandular morphogenesis is achieved by analyzing the phenotypes present in mice that harbor a spontaneous mutation, seminal vesicle shape (svs), previously identified for causing altered seminal vesicle morphology in adults. An examination of seminal vesicle development in svs mice provides the first evidence that the concurrent processes of epithelial branching and epithelial infolding are distinct processes under separate genetic control. It also provides the first direct evidence that the thickness and topology of the smooth muscle layer in the seminal vesicles are determined by interaction with the glandular epithelium during the branching process. In addition, the seminal vesicle phenotype in svs mice is shown to phenocopy the morphologic form present in certain other mammals such as the guinea pig, raising the possibility that the svs mutation is the sort of variant that arises during evolution. By also including an investigation of the prostate gland, this study also identifies previously unrecognized phenotypes in svs prostates, including increased gland size and dramatically reduced levels of branching morphogenesis. Finally, this study advances the goal of identifying the svs gene by mapping the svs mutation relative to known molecular markers and testing Fgfr2 as a candidate gene. The finding that the svs mutation maps to a genomic region syntenic to a region frequently deleted in human prostate tumors, together with the prostatic phenotype present in svs mice, further raises the interesting possibility that the svs mutation will identify a candidate prostate tumor suppressor gene. Developmental Dynamics 226:643,653, 2003. © 2003 Wiley-Liss, Inc. [source]

THE FITNESS EFFECTS OF SPONTANEOUS MUTATIONS IN CAENORHABDITIS ELEGANS

Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland

Effect of deletion of SOS-induced polymerases, pol II, IV, and V, on spontaneous mutagenesis in Escherichia coli mutD5

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2004
Anetta Nowosielska
Abstract The E. coli dnaQ gene encodes the , subunit of DNA polymerase III (pol III) responsible for the proofreading activity of this polymerase. The mutD5 mutant of dnaQ chronically expresses the SOS response and exhibits a mutator phenotype. In this study we have constructed a set of E. coli AB1157 mutD5 derivatives deleted in genes encoding SOS-induced DNA polymerases, pol II, pol IV, and pol V, and estimated the frequency and specificity of spontaneous argE3,Arg+ reversion in exponentially growing and stationary-phase cells of these strains. We found that pol II exerts a profound effect on the specificity of spontaneous mutation in exponentially growing cells. Analysis of growth-dependent Arg+ revertants in mutD5 polB+ strains revealed that Arg+ revertants were due to tRNA suppressor formation, whereas those in mutD5 ,polB strains arose by back mutation at the argE3 ochre site. In stationary-phase bacteria, Arg+revertants arose mainly by back mutation, regardless of whether they were proficient or deficient in pol II. Our results also indicate that in a mutD5 background, the absence of pol II led to increased frequency of Arg+ growth-dependent revertants, whereas the lack of pol V caused its dramatic decrease, especially in mutD5 ,umuDC and mutD5 ,umuDC ,polB strains. In contrast, the rate of stationary-phase Arg+revertants increased in the absence of pol IV in the mutD5 ,dinB strain. We postulate that the proofreading activity of pol II excises DNA lesions in exponentially growing cells, whereas pol V and pol IV are more active in stationary-phase cultures. Environ. Mol. Mutagen. 43:226,234, 2004. © 2004 Wiley-Liss, Inc. [source]

THE FITNESS EFFECTS OF SPONTANEOUS MUTATIONS IN CAENORHABDITIS ELEGANS

The sociobiology of biofilms

FEMS MICROBIOLOGY REVIEWS, Issue 1 2009
Carey D. Nadell
Abstract Biofilms are densely packed communities of microbial cells that grow on surfaces and surround themselves with secreted polymers. Many bacterial species form biofilms, and their study has revealed them to be complex and diverse. The structural and physiological complexity of biofilms has led to the idea that they are coordinated and cooperative groups, analogous to multicellular organisms. We evaluate this idea by addressing the findings of microbiologists from the perspective of sociobiology, including theories of collective behavior (self-organization) and social evolution. This yields two main conclusions. First, the appearance of organization in biofilms can emerge without active coordination. That is, biofilm properties such as phenotypic differentiation, species stratification and channel formation do not necessarily require that cells communicate with one another using specialized signaling molecules. Second, while local cooperation among bacteria may often occur, the evolution of cooperation among all cells is unlikely for most biofilms. Strong conflict can arise among multiple species and strains in a biofilm, and spontaneous mutation can generate conflict even within biofilms initiated by genetically identical cells. Biofilms will typically result from a balance between competition and cooperation, and we argue that understanding this balance is central to building a complete and predictive model of biofilm formation. [source]

A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy

GENES, BRAIN AND BEHAVIOR, Issue 7 2009
H. Suzuki
The lde/lde rat is characterized by dwarfism, postnatal lethality, male hypogonadism, a high incidence of epilepsy and many vacuoles in the hippocampus and amygdala. We used a candidate approach to identify the gene responsible for the lde phenotype and assessed the susceptibility of lde/lde rats for audiogenic seizures. Following backcross breeding of lethal dwarfism with epilepsy (LDE) to Brown Norway rats, the lde/lde rats with an altered genetic background showed all pleiotropic phenotypes. The lde locus was mapped to a 1.5-Mbp region on rat chromosome 19 that included the latter half of the Wwox gene. Sequencing of the full-length Wwox transcript identified a 13-bp deletion in exon 9 in lde/lde rats. This mutation causes a frame shift, resulting in aberrant amino acid sequences at the C-terminal. Western blotting showed that both the full-length products of the Wwox gene and its isoform were present in normal testes and hippocampi, whereas both products were undetectable in the testes and hippocampi of lde/lde rats. Sound stimulation induced epileptic seizures in 95% of lde/lde rats, with starting as wild running (WR), sometimes progressing to tonic,clonic convulsions. Electroencephalogram (EEG) analysis showed interictal spikes, fast waves during WR and burst of spikes during clonic phases. The Wwox protein is expressed in the central nervous system (CNS), indicating that abnormal neuronal excitability in lde/lde rats may be because of a lack of Wwox function. The lde/lde rat is not only useful for understanding the multiple functions of Wwox but is also a unique model for studying the physiological function of Wwox in CNS. [source]

Effects of sex chromosome aneuploidy on male sexual behavior

GENES, BRAIN AND BEHAVIOR, Issue 6 2008
J. H. Park
Incidence of sex chromosome aneuploidy in men is as high as 1:500. The predominant conditions are an additional Y chromosome (47,XYY) or an additional X chromosome (47,XXY). Behavioral studies using animal models of these conditions are rare. To assess the role of sex chromosome aneuploidy on sexual behavior, we used mice with a spontaneous mutation on the Y chromosome in which the testis-determining gene Sry is deleted (referred to as Y,) and insertion of a Sry transgene on an autosome. Dams were aneuploid (XXY,) and the sires had an inserted Sry transgene (XYSry). Litters contained six male genotypes, XY, XYY,, XXSry, XXY,Sry, XYSry and XYY,Sry. In order to eliminate possible differences in levels of testosterone, all of the subjects were castrated and received testosterone implants prior to tests for male sex behavior. Mice with an additional copy of the Y, chromosome (XYY,) had shorter latencies to intromit and achieve ejaculations than XY males. In a comparison of the four genotypes bearing the Sry transgene, males with two copies of the X chromosome (XXSry and XXY,Sry) had longer latencies to mount and thrust than males with only one copy of the X chromosome (XYSry and XYY,Sry) and decreased frequencies of mounts and intromissions as compared with XYSry males. The results implicate novel roles for sex chromosome genes in sexual behaviors. [source]

Quorum sensing controls biofilm formation in Vibrio cholerae

MOLECULAR MICROBIOLOGY, Issue 1 2003
Brian K. Hammer
Summary Multiple quorum-sensing circuits function in parallel to control virulence and biofilm formation in Vibrio cholerae. In contrast to other bacterial pathogens that induce virulence factor production and/or biofilm formation at high cell density in the presence of quorum-sensing autoinducers, V. cholerae represses these behaviours at high cell density. Consistent with this, we show here that V. cholerae strains ,locked' in the regulatory state mimicking low cell density are enhanced for biofilm production whereas mutants ,locked' in the regulatory state mimicking high cell density are incapable of producing biofilms. The quorum-sensing cascade we have identified in V. cholerae regulates the transcription of genes involved in exopolysaccharide production (EPS), and variants that produce EPS and form biofilms arise at high frequency from non-EPS, non-biofilm producing strains. Our data show that spontaneous mutation of the transcriptional regulator hapR is responsible for this effect. Several toxigenic strains of V. cholerae possess a naturally occurring frameshift mutation in hapR. Thus, the distinct environments occupied by this aquatic pathogen presumably include niches where cell-cell communication is crucial, as well as ones where loss of quorum sensing via hapR mutation confers a selective advantage. Bacterial biofilms could represent a complex habitat where such differentiation occurs. [source]

Sperm defects in mice lacking a functional Niemann,Pick C1 protein,

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 10 2006
Jun Fan
Abstract The Niemann,Pick C1 (NPC1) gene encodes for a multiple membrane spanning protein, which regulates the trafficking of low-density lipoprotein-mediated endocytosed cholesterol. Mutation of the human NPC1 gene causes Niemann,Pick type C (NPC) disease. The Npc1NIH mice, a model of human NPC disease, bear a spontaneous mutation of the Npc1 gene, and are infertile. In this study, we have performed sperm analysis to search for the cause of male infertility in the Npc1NIH mouse. The number of cauda sperms in Npc1,/, mice was decreased roughly three-and-half-fold of that in wild-type mice. The decreased sperm number in Npc1,/, mice is due, at least in part, to partial arrest of spermatogenesis in the testes, as revealed by histological analysis. Compared to wild-type sperm, Npc1,/, sperm displayed a high frequency of morphological abnormalities, including tailless heads and aberrant heads. In the in vitro fertilization (IVF) assay using cumulus-intact eggs, Npc1,/, sperm failed to produce two-cell embryos. In the IVF assay where zona-free eggs were used, Npc1,/, sperm bound normally but could not fuse with the egg. Further analysis indicated that Npc1,/, sperms are drastically impaired in the binding to the egg zona pellucida, only 14% of the level of wild-type sperm. Moreover, on Npc1,/, cauda sperm, one-third of the total cyritestin protein was not proteolytically processed, while fertilin , was processed normally. Taken together, these results demonstrate that there are multiple defects in sperms from mice lacking a functional NPC1 protein, and these observed sperm defects may result in sterility. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source]

Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG study

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2007
Claudia Gargini
Abstract Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517,525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches. J. Comp. Neurol. 500:222,238, 2007. © 2006 Wiley-Liss, Inc. [source]

A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene

CLINICAL ENDOCRINOLOGY, Issue 4 2001
D. Söderlund
BACKGROUND and OBJECTIVE Mutations in the GnRH receptor (GnRH-R) gene cause hypogonadotrophic hypogonadism. Here, we present the molecular studies of the GnRH-R gene in three families with isolated hypogonadotrophic hypogonadism. PATIENTS Three unrelated families, with at least two members diagnosed with isolated hypogonadotrophic hypogonadism were included. MEASUREMENTS DNA sequencing was performed after polymerase chain reaction amplification of each of the three exons of the gene. RESULTS A novel homozygous missense mutation, at nucleotide 268, turning glutamic acid into lysine, located at the second transmembrane domain of the GnRH-R gene was found in two patients pertaining to one of the families studied. Both parents and an unaffected brother were heterozygous carriers of one mutant allele, an unaffected sister was homozygote wild type. In the other two affected families no mutations were found in the GnRH-R gene. CONCLUSIONS This constitutes the first description of an spontaneous mutation located at the second transmembrane domain (Glu90Lys) of the GnRH-R, indicating that the integrity of glutamic acid at this position is crucial for receptor function. Also this report, complementing others, demonstrates that mutations are distributed throughout the GnRH-R gene and that as in the only other homozygous mutation previously described, affected patients present a complete form of hypogonadotrophic hypogonadism. Due to the fact that apparently consanguinity was present in our affected family, we presume that the mutation derived from a common ancestor, by a founder gene effect. [source]

THE CONTRIBUTION OF SPONTANEOUS MUTATION TO VARIATION IN ENVIRONMENTAL RESPONSES OF ARABIDOPSIS THALIANA: RESPONSES TO LIGHT

TOWARD A REALISTIC MODEL OF MUTATIONS AFFECTING FITNESS

EVOLUTION, Issue 3 2003
Peter D. Keightley
Abstract Analysis of a recent mutation accumulation (MA) experiment has led to the suggestion that as many as one-half of spontaneous mutations in Arabidopsis are advantageous for fitness. We evaluate this in the light of data from other MA experiments, along with molecular evidence, that suggest the vast majority of new mutations are deleterious. [source]

Allelic heterogeneity of molecular events in human coagulation factor IX in Asian Indians,,

HUMAN MUTATION, Issue 5 2007
Anubha Mahajan
Abstract Mutations in Factor IX gene (F9) cause X-linked recessive bleeding disorder hemophilia B. Here, we characterized molecular events in nine North Indian hemophiliac families identifying four missense mutations (three novel), two nonsense mutations, and a deletion. We have also captured the mutational spectrum of this disease in India based on available reports and established their genotype/phenotype relationships. Indian F9 mutations data indicate the absence of an important germline mutagen in the Indian subcontinent over the last century, and are consistent with previously made conclusions that universal, presumably endogenous factors are predominant in the causation of the spontaneous mutations in F9. We also analyzed the distribution of Ala194Thr polymorphism in 1231 Asian Indians and have established that Ala variant is far more frequent and can certainly be exploited for carrier detection, contrary to earlier reports. © 2007 Wiley-Liss, Inc [source]

Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2005
Nicole L. Lacz MD
Epidermolytic hyperkeratosis is an unusual type of ichthyosis. This inherited keratinization disorder is characterized clinically by erythema, blistering, and peeling shortly after birth. It may resolve and be replaced with thick scaling. It can lead to life-threatening complications, such as sepsis. Histologically, there is a hyperkeratosis and vacuolar degeneration. Genetically, this is an autosomal dominant disease with complete penetrance; however, 50% are spontaneous mutations. The clinical phenotype is a result of alterations in the gene(s) for keratin 1 and/or 10. We review this disorder and its therapy, which is mainly symptomatic with emollients and retinoids. [source]

Microsatellite instability and its relevance to cutaneous tumorigenesis

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2002
Mahmoud R. Hussein
Increasing evidence suggests that human tumors sequentially accumulate multiple mutations that cannot be explained by the low rates of spontaneous mutations in normal cells (2,3 mutations/cell). The mathematical models estimate that for the solid tumors to develop, as many as 6,12 mutations are required in each tumor cell. Therefore, to account for such high mutation rates, it is proposed that tumor cells are genetically unstable, i.e. they have genome-wide mutations at short repetitive DNA sequences called microsatellites. Microsatellite repeats are scattered throughout the human genome, primarily in the non-coding regions, and can give rise to variants with increased or reduced lengths, i.e. microsatellite instability (MSI). This instability has been reported in an increasing number of cutaneous tumors including: melanocytic tumors, basal cell carcinomas and primary cutaneous T-cell lymphomas. Moreover, MSI has been observed in skin tumors arising in the context of some hereditary disorders such as Muir,Torre syndrome, Von Recklinghausen's disease and disseminated superficial porokeratosis. While MSI in some of these disorders reflects underlying DNA replication errors, the mechanism of instability in others is still unknown. Thus far, MSI is considered to be a distinct tumorigenic pathway that reveals surprising versatility. The ramifications for cutaneous neoplasms warrant further investigation. [source]

Lifespan extension by dietary restriction is not linked to protection against somatic DNA damage in Drosophila melanogaster

AGING CELL, Issue 3 2009
Ursula Edman
Summary Dietary restriction (DR) has been shown to robustly extend lifespan in multiple species tested so far. The pro-longevity effect of DR is often ascribed to an increase in cellular defense against somatic damage, most notably damage by reactive oxygen species (ROS), considered a major cause of aging. Especially irreversible damage to DNA, the carrier of genetic information, is considered a critical causal factor in aging. Using a recently developed transgenic Drosophila melanogaster model system harboring a lacZ-plasmid construct that can be recovered in E. coli, spontaneous DNA mutation frequency in flies under DR and ad libitum conditions are measured. Three different DR conditions, imposed by manipulating levels of different types of yeast sources, were tested in females and males of two lacZ reporter gene lines. Feeding with the ROS producer paraquat at 1 mM resulted in a rapid accumulation of somatic mutations, indicating that the frequency of mutations at the lacZ locus is a reliable marker for increased oxidative stress. However, none of the DR conditions altered the accumulation of spontaneous mutations with age. These results suggest that the beneficial effects of DR are unlikely to be linked to protection against oxidative somatic DNA damage. [source]

Extensive Tinea in a Patient With Severe Combined Immunodeficiency

PEDIATRIC DERMATOLOGY, Issue 2 2009
RAFAEL JIMÉNEZ-PUYA M.D.
Although the X-linked recessive form is most common (60,70%), there are autosomal recessive forms (20%) and spontaneous mutations. While SCID may present with many nosocomial infections, dermatophyte infections are not common. We reported a case of SCID which was associated with a widespread skin infection with Trichophyton mentagrophytes. [source]