Search results for "Mutation."
showing 10 items of 2808 documents
Dynamic properties of some β-chain mutant hemoglobins
1995
The thermal behavior of the Soret band relative to the carbonmonoxy derivatives of some beta-chain mutant hemoglobins is studied in the temperature range 300-10 K and compared to that of wild-type carbonmonoxy hemoglobin. The band profile at various temperatures is modeled as a Voigt function that accounts for homogeneous broadening and for the coupling with high- and low-frequency vibrational modes, while inhomogeneous broadening is taken into account with a gaussian distribution of purely electronic transition frequencies. The various contributions to the over-all bandwidth are singled out with this analysis and their temperature dependence, in turn, gives information on structural and dy…
Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis
2016
Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Gα subunits of heterotrimeric G proteins. The mutations were det…
WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation
2014
International audience; BACKGROUND:Homozygous mutations in WWOX were reported in eight individuals of two families with autosomal recessive spinocerebellar ataxia type 12 and in two siblings with infantile epileptic encephalopathy (IEE), including one who deceased prior to DNA sampling.METHODS:By combining array comparative genomic hybridisation, targeted Sanger sequencing and next generation sequencing, we identified five further patients from four families with IEE due to biallelic alterations of WWOX.RESULTS:We identified eight deleterious WWOX alleles consisting in four deletions, a four base-pair frameshifting deletion, one missense and two nonsense mutations. Genotype-phenotype correl…
Diagnostic and therapeutic aspects of hemiplegic migraine
2020
Hemiplegic migraine (HM) is a clinically and genetically heterogeneous condition with attacks of headache and motor weakness which may be associated with impaired consciousness, cerebellar ataxia and intellectual disability. Motor symptoms usually last <72 hours and are associated with visual or sensory manifestations, speech impairment or brainstem aura. HM can occur as a sporadic HM or familiar HM with an autosomal dominant mode of inheritance. Mutations in CACNA1A, ATP1A2 and SCN1A encoding proteins involved in ion transport are implicated. The pathophysiology of HM is close to the process of typical migraine with aura, but appearing with a lower threshold and more severity. We review…
Untersuchungen �ber die alkalischen Serumphosphatasegruppen
1967
The alkaline serum phosphatase groups are determined in a sample of 218 unrelated Greek males and females. Two different methods have been applied: that given by Arfors et al. (1963), and that given by Shreffler (1965). Both of them yielded nearly identical results. This seems to be important in respect to the comparison of results obtained by application of different methods. The relationships between the alkaline serum phosphatase groups and the AB0 blood groups could be confirmed. Against that no relationships to Hp-, Gc-, Gm-, Inv- and Lp-groups were to be observed. Comparing the frequencies of alkaline serum phosphatase groups in different white populations (Swedes, US-Americans, Engli…
Experimental introgression to evaluate the impact of sex specific traits onDrosophila melanogasterincipient speciation
2019
ABSTRACTSex specific traits are involved in speciation but it is difficult to determine whether their variation initiates or reinforces sexual isolation. In some insects, speciation depends of the rapid change of expression in desaturase genes coding for sex pheromones. Two closely related desaturase genes are involved inDrosophila melanogasterpheromonal communication:desat1affects both the production and the reception of sex pheromones whiledesat2is involved in their production in flies of Zimbabwe populations. There is a strong asymmetric sexual isolation between Zimbabwe populations and all other “Cosmopolitan” populations: Zimbabwe females rarely copulate with Cosmopolitan males whereas…
Temperature-dependence of spontaneous mutation rates
2020
Mutation is the source of genetic variation and the fundament of evolution. At the interphase of ecology and evolution, temperature has long been suggested to have a direct impact on realised spontaneous mutation rates. The question is whether mutation rates can be a species-specific constant under variable environmental conditions, such as variation of the ambient temperature. By combining mutation accumulation with whole genome sequencing in a multicellular organism, we provide empirical support to reject this null hypothesis. Instead mutation rates depend on temperature in a U-shaped manner with increasing rates towards both temperature extremes. This relation has important implications …
Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy
2016
AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…
Evaluation of Fused Pyrrolothiazole Systems as Correctors of Mutant CFTR Protein.
2021
Cystic fibrosis (CF) is a genetic disease caused by mutations that impair the function of the CFTR chloride channel. The most frequent mutation, F508del, causes misfolding and premature degradation of CFTR protein. This defect can be overcome with pharmacological agents named “correctors”. So far, at least three different classes of correctors have been identified based on the additive/synergistic effects that are obtained when compounds of different classes are combined together. The development of class 2 correctors has lagged behind that of compounds belonging to the other classes. It was shown that the efficacy of the prototypical class 2 corrector, the bithiazole corr-4a, could be impr…
The pure descent statistic on permutations
2017
International audience; We introduce a new statistic based on permutation descents which has a distribution given by the Stirling numbers of the first kind, i.e., with the same distribution as for the number of cycles in permutations. We study this statistic on the sets of permutations avoiding one pattern of length three by giving bivariate generating functions. As a consequence, new classes of permutations enumerated by the Motzkin numbers are obtained. Finally, we deduce results about the popularity of the pure descents in all these restricted sets. (C) 2017 Elsevier B.V. All rights reserved.