Correction: Increasing The Yield In Targeted Next-Generation Sequencing By Implicating Cnv Analysis, Non-Coding Exons And The Overall Variant Load: The Example Of Retinal Dystrophies
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PROVIDER: S-EPMC4230913 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are major causes of blindness. They result from mutations in many genes which has long hampered comprehensive genetic analysis. Recently, targeted next-generation sequencing (NGS) has proven useful to overcome this limitation. To uncover "hidden mutations" such as copy number variations (CNVs) and mutations in non-coding regions, we extended the use of NGS data by quantitative readout for the exons of 55 RP and LCA genes in 126 patients, and by including non-coding 5' exons. We detected several causative CNVs which were key to the diagnosis in hitherto unsolved constellations, e.g. hemizygous point mutations in consanguineous families, and CNVs complemented apparently monoallelic recessive alleles. Mutations of non-coding exon 1 of EYS revealed its contribution to disease. In view of the high carrier frequency for retinal disease gene mutations in the general population, we considered the overall variant load in each patient to assess if a mutation was causative or reflected accidental carriership in patients with mutations in several genes or with single recessive alleles. For example, truncating mutations in RP1, a gene implicated in both recessive and dominant RP, were causative in biallelic constellations, unrelated to disease when heterozygous on a biallelic mutation background of another gene, or even non-pathogenic if close to the C-terminus. Patients with mutations in several loci were common, but without evidence for di- or oligogenic inheritance. Although the number of targeted genes was low compared to previous studies, the mutation detection rate was highest (70%) which likely results from completeness and depth of coverage, and quantitative data analysis. CNV analysis should routinely be applied in targeted NGS, and mutations in non-coding exons give reason to systematically include 5'-UTRs in disease gene or exome panels. Consideration of all variants is indispensable because even truncating mutations may be misleading.
| S-EPMC3827063 | biostudies-literature
Project description:The ability to alter the morphology of cattle towards greater yields of higher value primal cuts has the potential to increase the value of animals at slaughter. Using weight records of 14 primal cuts from 31,827 cattle, the objective of the present study was to quantify the extent of genetic variability in these primal cuts; also of interest was the degree of genetic variability in the primal cuts adjusted to a common carcass weight. Variance components were estimated for each primal cut using animal linear mixed models. The coefficient of genetic variation in the different primal cuts ranged from 0.05 (bavette) to 0.10 (eye of round) with a mean coefficient of genetic variation of 0.07. When phenotypically adjusted to a common carcass weight, the coefficient of genetic variation of the primal cuts was lesser ranging from 0.02 to 0.07 with a mean of 0.04. The heritability of the 14 primal cuts ranged from 0.14 (bavette) to 0.75 (topside) with a mean heritability across all cuts of 0.48; the heritability estimates reduced, and ranged from 0.12 (bavette) to 0.56 (topside), when differences in carcass weight were accounted for in the statistical model. Genetic correlations between each primal cut and carcass weight were all ≥0.77; genetic correlations between each primal cut and carcass conformation score were, on average, 0.59 but when adjusted to a common carcass weight, the correlations weakened to, on average, 0.27. The genetic correlations among all 14 primal cut weights was, on average, strong (mean correlation of 0.72 with all correlations being ≥0.37); when adjusted to a common carcass weight, the mean of the genetic correlations among all primal cuts was 0.10. The ability of estimated breeding values for a selection of primal cuts to stratify animals phenotypically on the respective cut weight was demonstrated; the weight of the rump, striploin, and fillet of animals estimated to be in the top 25% genetically for the respective cut, were 10 to 24%, 12 to 24%, and 7 to 17% heavier than the weight of cuts from animals predicted to be in the worst 25% genetically for that cut. Significant exploitable genetic variability in primal carcass cuts was clearly evident even when adjusted to a common carcass weight. The high heritability of many of the primal cuts infers that large datasets are not actually required to achieve high accuracy of selection once the structure of the data and the number of progeny per sire is adequate.
| S-EPMC6606483 | biostudies-literature
Project description:Transgenic rice plants expressing the Arabidopsis phloem-specific sucrose transporter AtSUC2, which loads Suc into the phloem, showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. The goal was to reveal how expressed AtSUC2 in rice leads to increased grain yield analyzing global gene expression.
2015-10-21 | GSE74204 | GEO
Project description:Microorganisms primarily utilize nutrients to generate biomass and replicate. When a single nutrient source is available, the produced biomass typically increases linearly with the initial amount of that nutrient. This linear trend can be accurately predicted by "black box models", which conceptualize growth as a single chemical reaction, treating nutrients as substrates and biomass as a product. However, natural environments usually present multiple nutrient sources, prompting us to extend the black box framework to incorporate catabolism, anabolism, and biosynthesis of biomass precursors. This modification allows for the quantification of co-utilization effects among multiple nutrients on microbial biomass production. The extended model differentiates between different types of nutrients: non-degradable nutrients, which can only serve as a biomass precursor, and degradable nutrients, which can also be used as an energy source. We experimentally demonstrated using Escherichia coli that, in contrast to initial model predictions, different nutrients affect each other's utilization in a mutually dependent manner; i.e., for some combinations, the produced biomass was no longer proportional to the initial amounts of nutrients present. To account for these mutual effects within a black box framework, we phenomenologically introduced an interaction between the metabolic processes involved in utilizing the nutrient sources. This phenomenological model qualitatively captures the experimental observations and, unexpectedly, predicts that the total produced biomass is influenced not only by the combination of nutrient sources but also by their relative initial amounts - a prediction we subsequently validated experimentally. Moreover, the model identifies which metabolic processes - catabolism, anabolism, or precursor biosynthesis-is affected in each specific nutrient combination, offering insights into microbial metabolic coordination.
| S-EPMC11811147 | biostudies-literature
Project description:Brush cytology is a sampling technique extensively used for mucosal surfaces, particularly to identify malignancies. A sample is obtained by rubbing the brush bristles over the stricture or lesion several times until cells are trapped. Brush cytology detection rate varies, with malignancy confirmed in 15-65% of cases of adenocarcinoma-associated biliary strictures and 44-80% of cases of cholangiocarcinoma. Despite the widespread use of brush cytology, there is no consensus to date defining the optimal biliary brushing parameters for the collection of suspicious lesions, such as the number of passes, brushing rate, and force applied. The aim of this work is to increase the brush cytology diagnostic yield by elucidating the underlying mechanical phenomena. First, the mechanical interactions between the brush bristles and sampled tissue are analyzed. During brushing, mucus and detached cells are transferred to the space between the bristles through the capillary rise and flow eddies. These mass transfer mechanisms and their dependence on mucus rheology as a function of pH, brush displacement rate, and bristle geometry and configuration are examined. Lastly, results from ex vivo brushing experiments performed on porcine stomachs are presented. Clinical practitioners from a variety of disciplines can apply the findings of this study to outline clear procedures for cytological brushing to increase the sensitivity and specificity of the brushings.
| S-EPMC10934267 | biostudies-literature
Project description:Muscular dystrophy patient and control samples
| PRJEB48580 | ENA
Project description: Not available
| S-EPMC4069171 | biostudies-literature
Project description:To investigate the effects of increasing axial load on cervical motor control. Surrogates of cervical motor control were active cervical range of motion (C-ROM) and joint position error (JPE) assessed in flexion, extension, lateroflexion and rotation directions in 49 healthy young men (mean age: 20.2 years). All measurements were executed with 0-, 1-, 2-, and 3-kg axial loads. Linear mixed models were used to assess the effects of axial loading and cervical movement-direction on C-ROM and JPE. Post-hoc analysis was performed to compare load levels. Axial loading (p = 0.045) and movement direction (p < 0.001) showed significant main effects on C-ROM as well as an interaction (p < 0.001). C-ROM significantly changed with 3-kg axial load by decreaseing extension (- 13.6%) and increasing lateroflexion (+ 9.9%). No significant main effect was observed of axial loading on JPE (p = 0.139). Cervical motor control is influenced by axial loading, which results in decreased C-ROM in extension and increased C-ROM lateroflexion direction.
| S-EPMC8452641 | biostudies-literature
Project description:The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy. In this study, we investigated whole genome sequencing (WGS), focused assays and functional studies to assist with unsolved IRD cases and facilitate integration of these approaches to a broad molecular diagnostic clinical service. The WGS approach identified variants not covered or underinvestigated by targeted capture panel-based clinical testing strategies in six families. This included structural variants, with notable benefit of the WGS approach in repetitive regions demonstrated by a family with a hybrid gene and hemizygous missense variant involving the opsin genes, OPN1LW and OPN1MW. There was also benefit in investigation of the repetitive GC-rich ORF15 region of RPGR. Further molecular investigations were facilitated by focused assays in these regions. Deep intronic variants were identified in IQCB1 and ABCA4, with functional RNA based studies of the IQCB1 variant revealing activation of a cryptic splice acceptor site. While targeted capture panel-based methods are successful in achieving an efficient molecular diagnosis in a proportion of cases, this study highlights the additional benefit and clinical value that may be derived from WGS, focused assays and functional genomics in the highly heterogeneous IRDs.
| S-EPMC8999823 | biostudies-literature
Project description:BackgroundThough abnormal iron deposition has been reported in specific brain regions in multiple sclerosis (MS), no data exist about whether the overall quantity of iron in the brain is altered or not. We aimed to determine whether the noted aberrant iron deposition in MS brains was a problem of overall load or regional distribution in a cohort of MS patients.MethodsAn experienced neuroradiologist, a radiology software engineer, and four neurologists analysed data from quantitative susceptibility maps reconstructed from 3-T magnetic resonance brain images of 30 MS patients and 15 age- and sex-matched healthy controls. Global brain iron load was calculated, and the regional iron concentrations were assessed in 1,000 regions of interest placed in MS lesions in different locations, normal appearing white matter, thalami, and basal ganglia.ResultsGlobal brain iron load was comparable between patients and controls after adjustment for volume (p = 0.660), whereas the regional iron concentrations were significantly different in patients than in control (p ≤ 0.031). There was no significant correlation between global iron load and clinical parameters, whereas regional iron concentrations correlated with patients' age, disease duration, and disability grade (p ≤ 0.039).ConclusionsThe aberrant iron deposition noted in MS seems to be a problem of regional distribution rather than an altered global brain iron load.
| S-EPMC9458829 | biostudies-literature