Academia.edu no longer supports Internet Explorer.
To browse Academia.edu and the wider internet faster and more securely, please take a few seconds to upgrade your browser.
2016, Annals of Neurology
ObjectiveThe polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases.MethodsWe assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study.ResultsIn the analysis of DNA repair genes ...
Medycyna wieku rozwojowego
[Mutations causing hereditary hyperphenylalaninemia]Mutations in the genes encoding different parts of phenylalanine hydroxylation system cause persistent hyperphenylalaninaemia. The most frequent form of hyperphenylalaninaemia is caused by mutations in the PAH gene. The most common variant result from defect of tetrahydrobiopterin synthase. Mutations in the PAH and PTS genes in the Polish population are presented. Genotype--phenotype correlations are discussed.
1983 •
A polymorphic DNA marker genetically linked to Huntington's disease James F. Gusella*, Nancy S. Wexlert|!, P. Michael Conneally\ Susan L. Naylor', Mary Anne ...
Infection, Genetics and Evolution
Proteome size reduction in Apicomplexans is linked with loss of DNA repair and host redundant pathways2021 •
Apicomplexans are alveolate parasites which include Plasmodium falciparum, the main cause of malaria, one of the world’s biggest killers from infectious disease. Apicomplexans are characterized by a reduction in proteome size, which appears to result from metabolic and functional simplification, commensurate with their parasitic lifestyle. However, other factors may also help to explain gene loss such as population bottlenecks experienced during transmission, and the effect of reducing the overall genomic information content. The latter constitutes an ‘informational constraint’, which is proposed to exert a selective pressure to evolve and maintain genes involved in informational fidelity and error correction, proportional to the quantity of information in the genome (which approximates to proteome size). The dynamics of gene loss was examined in 41 Apicomplexan genomes using orthogroup analysis. We show that loss of genes involved in amino acid metabolism and steroid biosynthesis can be explained by metabolic redundancy with the host. We also show that there is a marked tendency to lose DNA repair genes as proteome size is reduced. This may be explained by a reduction in size of the informational constraint and can help to explain elevated mutation rates in pathogens with reduced genome size. Multiple Sequentially Markovian Coalescent (MSMC) analysis indicates a recent bottleneck, consistent with predictions generated using allele-based population genetics approaches, implying that relaxed selection pressure due to reduced population size might have contributed to gene loss. However, the non-randomness of pathways that are lost challenges this scenario. Lastly, we identify unique orthogroups in malaria-causing Plasmodium species that infect humans, with a high proportion of membrane associated proteins. Thus, orthogroup analysis appears useful for identifying novel candidate pathogenic factors in parasites, when there is a wide sample of genomes available.
Human molecular genetics
A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)2015 •
Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (∼660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adopti...
Biologie aujourd'hui
[Epigenetic mechanisms and alcohol use disorders: a potential therapeutic target]2017 •
Alcohol use disorder is a devastating illness with a profound health impact, and its development is dependent on both genetic and environmental factors. This disease occurs over time and requires changes in brain gene expression. There is converging evidence suggesting that the epigenetic processes may play a role in the alcohol-induced gene regulations and behavior such as the intervention of DNA methylation and histone acetylation. Histone acetylation, like histone methylation, is a highly dynamic process regulated by two classes of enzymes: histone acetyltransferases and histone deacetylases (HDACs). To date, 18 human HDAC isoforms have been characterized, and based on their sequence homologies and cofactor dependencies, they have been phylogenetically categorized into 4 main classes: classes I, II (a and b), III, and IV. In the brain, expression of the different classes of HDACs varies between cell types and also in their subcellular localization (nucleus and/or cytosol). Furthe...
Médecine sciences : M/S
[Direct role of p53 on homologous recombination]2005 •
The tumor suppressor gene p53, which is the most frequently mutated gene in human tumors, controls cell cycle checkpoint and apoptosis via the transactivation of the transcription of a collection of genes. These activities avoid proliferation of cell bearing alteration of genetic material. However, like a two-edged sword, p53 can also directly participate to genome stability maintenance by repressing homologous recombination (HR), independently of the transactivation activity. This parallel activity allows to limit the deleterious consequences on an excess of HR. Beside genetic interactions, p53 protein physically interacts with both HR proteins and HR intermediates (heteroduplex and Holliday junctions). The core domain of p53 is required for interaction with Rad51 at an early step and the carboxy-terminal domain of p53 is involved in the interaction with Rad54 and HR intermediates, at a late step. We discuss here the putative consequences of this parallel activity of p53 on genome ...
Université de Sherbrooke
Identification et impacts des anomalies génétiques dans la genèse, l'évolution clinique et le traitement des gliomes2010 •
Social Sciences Studies Journal (SSSJournal) Dergisi, Cilt 4 Sayı : 17, Mayıs 2018
Akıllı ve Ekolojik Kentlerle Sürdürülebilir Kentsel Tasarım: "Arazi Bilgi Yönetimi Sistemi (ABYS)" ve “Mülkiyet ve İmar Hakki Aktarimi (MİHAM)"2018 •
Early Science and Medicine
The Discovery of chreia: Galen's Method of Teleological Demonstration and Its Aristotelian Background2024 •
Bolívar Echeverría: modernidad y resistencias
Discurso crítico, modernidad y resistencia2015 •
HAL (Le Centre pour la Communication Scientifique Directe)
Transformation as Practice: Learning From Everyday Dealings With Groundwater2023 •
Revista Izquierdas
Figuras de la realización de la filosofía en Karl Korsch y la Teoría Crítica. En el centenario de la publicación de 'Marxismo y filosofía' (2024)2024 •
Centre for Land Warfare Studies (CLAWS)
Militarisation of 5G: A Necessity for the Forces2021 •
Engineering Journal of Satbayev University
New Technologies in Mining Sustainable Production. Tailings Management and Mining ChemicalsJournal of Experimental and Clinical Medicine
Hipokrat 2000 total knee arthroplasty in gonarthrosis:Midterm follow-up results2012 •
Journal of Petroleum & Environmental Biotechnology
Potential of New Microbial Isolates for Biosurfactant Production using Combinations of Distillery Waste with other Industrial Wastes2013 •
IEEE Transactions on Microwave Theory and Techniques
Avalanche Microwave Noise Sources in Commercial 90-nm CMOS Technology2016 •