Search results for "Susceptibility"
showing 10 items of 912 documents
Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss.
2015
Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium-and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both…
PSD3 downregulation confers protection against fatty liver disease
2022
Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cell…
MHC class II genes influence the susceptibility to chronic active hepatitis C
1997
Chronic hepatitis C develops in more than 70% of hepatitis C virus infected subjects. Viral factors influence the disease course, but little is known about the importance of host factors.Frequencies of major histocompatibility complex (MHC) class I and class II antigens were analyzed in two groups of patients with chronic hepatitis C virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotyping was done by PCR based typing methods.DRB1*0301 was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%) and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p0.001). Homozygosity for this allel…
Human SPG11 cerebral organoids reveal cortical neurogenesis impairment
2018
Abstract Spastic paraplegia gene 11(SPG11)-linked hereditary spastic paraplegia is a complex monogenic neurodegenerative disease that in addition to spastic paraplegia is characterized by childhood onset cognitive impairment, thin corpus callosum and enlarged ventricles. We have previously shown impaired proliferation of SPG11 neural progenitor cells (NPCs). For the delineation of potential defect in SPG11 brain development we employ 2D culture systems and 3D human brain organoids derived from SPG11 patients’ iPSC and controls. We reveal that an increased rate of asymmetric divisions of NPCs leads to proliferation defect, causing premature neurogenesis. Correspondingly, SPG11 organoids appe…
Developing the "next generation" of genetic association databases for complex diseases
2012
Tens of thousands of genetic association studies investigating the influence of common polymorphisms on disease susceptibility have been published to date. These include similar to 1,000 genome-wide association studies (GWAS). This vast amount of data in the field of complex genetics is becoming increasingly difficult to follow and interpret. It can be expected that the situation will become even more complex with the advent of association projects using next-generation technologies. One of the aims of the Human Variome Project is to concatenate such data in meaningful ways, for example, within the context of publicly available field synopses. Here, we present various examples of online gen…
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.
2014
Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for stud…
Gully erosion susceptibility mapping using GIS-based multi-criteria decision analysis techniques
2019
Abstract This research introduces a scientific methodology for gully erosion susceptibility mapping (GESM) that employs geography information system (GIS)-based multi-criteria decision analysis. The model was tested in Semnan Province, Iran, which has an arid and semi-arid climate with high susceptibility to gully erosion. The technique for order of preference by similarity to ideal solution (TOPSIS) and the analytic hierarchy process (AHP) multi-criteria decision-making (MCDM) models were integrated. The important aspect of this research is that it did not require gully erosion inventory maps for GESM. Therefore, the proposed methodology could be useful in areas with missing or incomplete …
An orbital floating time scale of the Hauterivian/Barremian GSSP from a magnetic susceptibility signal (Río Argos, Spain).
2012
10 pages; International audience; An orbital floating time scale of the HauterivianeBarremian transition (Early Cretaceous) is proposed using high-resolution magnetic susceptibility measurements. Orbital tuning was performed on the Río Argos section (southeast Spain), the candidate for a Global boundary Stratotype Section and Point (GSSP) for the HauterivianeBarremian transition. Spectral analyses of MS variations, coupled with the frequency ratio method, allow the recognition of precession, obliquity and eccentricity frequency bands. Orbitallytuned magnetic susceptibility provides minimum durations for ammonite biozones. The durations of well-constrained ammonite zones are assessed at 0.78…
Combination of geo- pedo- and technogenic magnetic and geochemical signals in soil profiles - Diversification and its interpretation: A new approach.
2016
Magnetic and geochemical parameters of soils are determined with respect to geology, pedogenesis and anthropopression. Depending on local conditions these factors affect magnetic and geochemical signals simultaneously or in various configurations. We examined four type of soils (Entic Podzol, Eutric Cambisol, Humic Cambisol and Dystric Cambisol) developed on various bedrock (the Tumlin Sandstone, basaltoid, amphibolite and serpentinite, respectively). Our primary aim was to characterize the origin and diversification of the magnetic and geochemical signal in soils in order to distinguish the most reliable methods for correct interpretation of measured parameters. Presented data include sele…
Cloud-based interactive susceptibility modeling of gully erosion in Google Earth Engine
2022
The gully erosion susceptibility literature is largely dominated by contributions focused on model comparison. This has led to prioritize certain aspects and leave others underdeveloped as compared to other natural hazard applications. For instance, in gully erosion data-driven modeling most studies use different platforms when it comes to data management, modeling and conversion into predictive maps. This in turn has limited the scope to catchment-scales. In this manuscript, we opt to propose a tool where the whole modeling procedure is unified within the same cloud computing system, allowing one to get rid of potential errors caused by input/output operations but also to extend the study …