Search results for "Hap"
showing 10 items of 2767 documents
A low-frequency haplotype spanning SLX4/FANCP constitutes a new risk locus for early-onset breast cancer (<60 years) and is associated with reduce…
2017
Only a fraction of breast cancer (BC) cases can be yet explained by mutations in genes or genomic variants discovered in linkage, genome-wide association and sequencing studies. The known genes entailing medium or high risk for BC are strongly enriched for a function in DNA double strand repair. Thus, aiming at identifying low frequency variants conferring an intermediate risk, we here investigated 17 variants (MAF: 0.01-0.1) in 10 candidate genes involved in DNA repair or cell cycle control. In an exploration cohort of 437 cases and 1189 controls, we show the variant rs3810813 in the SLX4/FANCP gene to be significantly associated with both BC (≤60 years; OR = 2.6(1.6-3.9), p = 1.6E-05) and…
Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity
2021
PURPOSE: ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized.METHODS: International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing.RESULTS: We identified 13 individuals with heterozygous…
Zebrafish as a Model for the Study of Chaperonopathies
2016
There is considerable information on the clinical manifestations and mode of inheritance for many genetic chaperonopathies but little is known on the molecular mechanisms underlying the cell and tissue abnormalities that characterize them. This scarcity of knowledge is mostly due to the lack of appropriate animal models that mimic closely the human molecular, cellular, and histological characteristics. In this article we introduce zebrafish as a suitable model to study molecular and cellular mechanisms pertaining to human chaperonopathies. Genetic chaperonopathies manifest themselves from very early in life so it is necessary to examine the impact of mutant chaperone genes during developmen…
Haplotype reference consortium panel: Practical implications of imputations with large reference panels.
2017
Contains fulltext : 177754.pdf (Publisher’s version ) (Open Access) Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts usin…
Effects of alternative electron acceptors on the activity and community structure of methane-producing and consuming microbes in the sediments of two…
2017
The role of anaerobic CH4 oxidation in controlling lake sediment CH4 emissions remains unclear. Therefore, we tested how relevant EAs (SO42−, NO3−, Fe3+, Mn4+, O2) affect CH4 production and oxidation in the sediments of two shallow boreal lakes. The changes induced to microbial communities by the addition of Fe3+ and Mn4+ were studied using next-generation sequencing targeting the 16S rRNA and methyl-coenzyme M reductase (mcrA) genes and mcrA transcripts. Putative anaerobic CH4-oxidizing archaea (ANME-2D) and bacteria (NC 10) were scarce (up to 3.4% and 0.5% of archaeal and bacterial 16S rRNA genes, respectively), likely due to the low environmental stability associated with shallow depths.…
Association of leisure time physical activity and NMR-detected circulating amino acids in peripubertal girls: A 7.5-year longitudinal study
2017
AbstractThis study investigated the longitudinal associations of physical activity and circulating amino acids concentration in peripubertal girls. Three hundred ninety-six Finnish girls participated in the longitudinal study from childhood (mean age 11.2 years) to early adulthood (mean age 18.2 years). Circulating amino acids were assessed by nuclear magnetic resonance spectroscopy. LTPA was assessed by self-administered questionnaire. We found that isoleucine, leucine and tyrosine levels were significantly higher in individuals with lower LTPA than their peers at age 11 (p < 0.05 for all), independent of BMI. In addition, isoleucine and leucine levels increased significantly (~15%) fro…
Chaperonin of Group I: Oligomeric spectrum and biochemical and biological implications
2018
Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM), is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still inc…
DNA multigene characterization of Fasciola hepatica and Lymnaea neotropica and its fascioliasis transmission capacity in Uruguay, with historical cor…
2017
Background Fascioliasis is a pathogenic disease transmitted by lymnaeid snails and recently emerging in humans, in part due to effects of climate changes, anthropogenic environment modifications, import/export and movements of livestock. South America is the continent presenting more human fascioliasis hyperendemic areas and the highest prevalences and intensities known. These scenarios appear mainly linked to altitude areas in Andean countries, whereas lowland areas of non-Andean countries, such as Uruguay, only show sporadic human cases or outbreaks. A study including DNA marker sequencing of fasciolids and lymnaeids, an experimental study of the life cycle in Uruguay, and a review of hum…
Missense Mutations of Human Hsp60: A Computational Analysis to Unveil Their Pathological Significance
2020
Two chaperonopathies have been linked to mutations in the human hsp60 (hHsp60; HSPD1) gene, but other existing variants might cause diseases, even if there is no comprehensive information about this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single hsp60 gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possi…
The neurochaperonopathies: Anomalies of the chaperone system with pathogenic effects in neurodegenerative and neuromuscular disorders
2021
The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic …