Haplotype estimation in polyploids using DNA sequence data

Polyploid organisms possess more than two copies of their core genome and therefore contain k>2 haplotypes for each set of ordered genomic variants. Polyploidy occurs often within the plant kingdom, among others in important corps such as potato (k=4) and wheat (k=6). Current sequencing technologies enable us to read the DNA and detect genomic variants, but cannot distinguish between the copies of the genome, each inherited from one of the parents. To detect inheritance patterns in populations, it is necessary to know the haplotypes, as alleles that are in linkage over the same chromosome tend to be inherited together. In this work, we develop mathematical optimisation algorithms to indirectly estimate haplotypes by looking into overlaps between the sequence reads of an individual, as well as into the expected inheritance of the alleles in a population. These algorithm deal with sequencing errors and random variations in the counts of reads observed from each haplotype. These methods are therefore of high importance for studying the genetics of polyploid crops. </p

Family-Based Haplotype Estimation and Allele Dosage Correction for Polyploids Using Short Sequence Reads

DNA sequence reads contain information about the genomic variants located on a single chromosome. By extracting and extending this information using the overlaps between the reads, the haplotypes of an individual can be obtained. Using parent-offspring relationships in a population can considerably improve the quality of the haplotypes obtained from short reads, as pedigree information can be used to correct for spurious overlaps (due to sequencing errors) and insufficient overlaps (due to short read lengths, low genomic variation and shallow coverage). We developed a novel method, PopPoly, to estimate polyploid haplotypes in an F1-population from short sequence data by taking into consideration the transmission of the haplotypes from the parents to the offspring. In addition, this information is employed to improve genotype dosage estimation and to call missing genotypes in the population. Through simulations, we compare PopPoly to other haplotyping methods and show its better performance. We evaluate PopPoly by applying it to a tetraploid potato cross at nine genomic regions involved in tuber formation

The Formation of the Administrative Remedy System in Taiwan under Japanese Colonial Rule

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Socioeconomic inequalities in type 2 diabetes : mediation through status anxiety?

Published online: 02 October 2023-- Objectives: While status anxiety has received attention as a potential mechanism generating health inequalities, empirical evidence is still limited. Studies have been ecological and have largely focused on mental and not physical health outcomes. -- Methods: We conducted individual-level analyses to assess status anxiety (feelings of inferiority resulting from social comparisons) and resources (financial difficulties) as mediators of the relationship between socioeconomic status (SES) (education/occupation/employment status) and type 2 diabetes (T2D). We used cross-sectional data of 21,150 participants (aged 18–70 years) from the Amsterdam-based HELIUS study. We estimated associations using logistic regression models and estimated mediated proportions using natural effect modelling. -- Results: Odds of status anxiety were higher among participants with a low SES [e.g., OR = 2.66 (95% CI: 2.06–3.45) for elementary versus academic occupation]. Odds of T2D were 1.49 (95% CI: 1.12–1.97) times higher among participants experiencing status anxiety. Proportion of the SES–T2D relationship mediated was 3.2% (95% CI: 1.5%–7.0%) through status anxiety and 10.9% (95% CI: 6.6%–18.0%) through financial difficulties. -- Conclusion: Status anxiety and financial difficulties played small but consistent mediating roles. These individual-level analyses underline status anxiety’s importance and imply that status anxiety requires attention in efforts to reduce health inequalities

Exploiting Next Generation Sequencing to solve the Haplotyping puzzle in Polyploids

Evaluation of single genome haplotyping methods in polyploids through a simulation stud

beta-Amyloid Precursor Protein and Ubiquitin Cross Mark Immunohistochemistry Aid in the Evaluation of Infant Autopsy Eyes With Abusive Head Trauma

PURPOSE: To investigate beta-amyloid precursor protein (beta-APP), ubiquitin, and glial fibrillary acid protein (GFAP) immunostaining as a diagnostic tool to aid in the discrimination between abusive head trauma and nonabusive head trauma in postmortem ocular histopathologic investigation. DESIGN: Retrospective cross-sectional study. METHODS: Seventy-four eyes of 37 infants were studied for hemorrhage and immunohistochemical expression of beta-APP, ubiquitin, and GFAP in the retina and optic nerve. Infants were assigned to abusive head trauma or control groups, according to published criteria. RESULTS: In the abusive head trauma group, positive beta-APP and ubiquitin immunostaining of the retina was significantly more likely to be found than in the control group, odds ratio (OR) 11.4, confidence interval (CI) 2.9-44.3; P < .001 and OR 8.8, CI 2.2-34.5; P = .002, respectively. Positive correlations were found between retinal expression of beta-APP and ubiquitin immunostaining and retinal hemorrhage. Vitreal hemorrhages, orbital fat hemorrhages, and macular folds could only be identified in abusive head trauma cases. Retinal hemorrhages were significantly more severe, occupied a larger proportion of the retina, and involved more retinal layers in abusive head trauma compared to controls (OR 2.7, CI 1.7-4.4; P < .001). CONCLUSIONS: This study shows correlations between positive retinal beta-APP and ubiquitin immunostaining as a sign of axonal injury in abusive head trauma. Axonal injury is a useful pathologic feature that can be demonstrated in postmortem ocular investigation of deceased children using immunohistochemical staining for beta-APP and ubiquitin with a high OR for abusive head trauma when compared to controls. (C) 2015, by Elsevier Inc. All rights reserved

beta-Amyloid Precursor Protein and Ubiquitin Cross Mark Immunohistochemistry Aid in the Evaluation of Infant Autopsy Eyes With Abusive Head Trauma

PURPOSE: To investigate beta-amyloid precursor protein (beta-APP), ubiquitin, and glial fibrillary acid protein (GFAP) immunostaining as a diagnostic tool to aid in the discrimination between abusive head trauma and nonabusive head trauma in postmortem ocular histopathologic investigation. DESIGN: Retrospective cross-sectional study. METHODS: Seventy-four eyes of 37 infants were studied for hemorrhage and immunohistochemical expression of beta-APP, ubiquitin, and GFAP in the retina and optic nerve. Infants were assigned to abusive head trauma or control groups, according to published criteria. RESULTS: In the abusive head trauma group, positive beta-APP and ubiquitin immunostaining of the retina was significantly more likely to be found than in the control group, odds ratio (OR) 11.4, confidence interval (CI) 2.9-44.3; P < .001 and OR 8.8, CI 2.2-34.5; P = .002, respectively. Positive correlations were found between retinal expression of beta-APP and ubiquitin immunostaining and retinal hemorrhage. Vitreal hemorrhages, orbital fat hemorrhages, and macular folds could only be identified in abusive head trauma cases. Retinal hemorrhages were significantly more severe, occupied a larger proportion of the retina, and involved more retinal layers in abusive head trauma compared to controls (OR 2.7, CI 1.7-4.4; P < .001). CONCLUSIONS: This study shows correlations between positive retinal beta-APP and ubiquitin immunostaining as a sign of axonal injury in abusive head trauma. Axonal injury is a useful pathologic feature that can be demonstrated in postmortem ocular investigation of deceased children using immunohistochemical staining for beta-APP and ubiquitin with a high OR for abusive head trauma when compared to controls. (C) 2015, by Elsevier Inc. All rights reserved

Exercise self-efficacy is weakly related to engagement in physical activity in persons with long-standing spinal cord injury

Aims: Many people with a long-standing spinal cord injury have an inactive lifestyle. Although exercise self-efficacy is considered a key determinant of engaging in exercise, the relationship between exercise self-efficacy and physical activity remains unclear. Therefore, this study examines the relationship between exercise self-efficacy and the amount of physical activity in persons with long-standing spinal cord injury. Methods: This cross-sectional study included 268 individuals (aged 28–65 years) with spinal cord injury ≥ 10 years and using a wheelchair. Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities. Exercise self-efficacy was assessed with the Spinal cord injury Exercise Self-Efficacy Scale. Univariate and multivariable regression analyses were performed to test for the association between exercise self-efficacy and physical activity, controlling for supposed confounders. Results: Univariate regression analysis revealed that exercise self-efficacy was significantly related to the level of daily physical activity (β = 0.05; 95% CI 0.04–0.07; 15% explained variance; p < 0.001). In multivariable regression analysis exercise self-efficacy remained, explaining a significant additional amount of the variance (2%; p < 0.001) of physical activity. Conclusion: Exercise-self efficacy is a weak but independent explanatory factor of the level of physical activity among persons with long-standing spinal cord injury. Longitudinal trials are needed to study the impact of interventions targeting an increase of exercise self-efficacy on the amount of physical activity performed.Implications for rehabilitation Pre-intervention levels of exercise-self-efficacy might mediate the effectiveness of interventions that aim at increasing physical activities in people with a long-standing spinal cord injury. Enhancing exercise-self efficacy may improve levels of physical activity, even in people with a long-standing spinal cord injury. When it comes to enhancing physical activity, efforts to enhance non-structured daily physical activities such as household activities and gardening might be as important as efforts to enhance sports and other physical exercise.</p

TriPoly : haplotype estimation for polyploids using sequencing data of related individuals

Motivation: Knowledge of haplotypes, i.e. phased and ordered marker alleles on a chromosome, is essential to answer many questions in genetics and genomics. By generating short pieces of DNA sequence, high-throughput modern sequencing technologies make estimation of haplotypes possible for single individuals. In polyploids, however, haplotype estimation methods usually require deep coverage to achieve sufficient accuracy. This often renders sequencing-based approaches too costly to be applied to large populations needed in studies of Quantitative Trait Loci. Results: We propose a novel haplotype estimation method for polyploids, TriPoly, that combines sequencing data with Mendelian inheritance rules to infer haplotypes in parent-offspring trios. Using realistic simulations of both short and long-read sequencing data for banana (Musa acuminata) and potato (Solanum tuberosum) trios, we show that TriPoly yields more accurate progeny haplotypes at low coverages compared to existing methods that work on single individuals. We also apply TriPoly to phase Single Nucleotide Polymorphisms on chromosome 5 for a family of tetraploid potato with 2 parents and 37 offspring sequenced with an RNA capture approach. We show that TriPoly haplotype estimates differ from those of the other methods mainly in regions with imperfect sequencing or mapping difficulties, as it does not rely solely on sequence reads and aims to avoid phasings that are not likely to have been passed from the parents to the offspring. Availability and implementation: TriPoly has been implemented in Python 3.5.2 (also compatible with Python 2.7.3 and higher) and can be freely downloaded at https://github.com/EhsanMotazedi/TriPoly. Supplementary information: Supplementary data are available at Bioinformatics online.</p