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Frontiers in Genetics 2023Optical genome mapping (OGM), which allows analysis of ultra-high molecular weight (UHMW) DNA molecules, represents a response to the restriction created by short-read...
Optical genome mapping (OGM), which allows analysis of ultra-high molecular weight (UHMW) DNA molecules, represents a response to the restriction created by short-read next-generation-sequencing, even in cases where the causative variant is a neutral copy-number-variant insensitive to quantitative investigations. This study aimed to provide a molecular diagnosis to a boy with Marfan syndrome (MFS) and intellectual disability (ID) carrying a translocation involving chromosomes 3, 4, and 13 and a 1.7 Mb deletion at the breakpoint of chromosome 3. No alteration explaining his Marfan phenotype was highlighted. UHMW gDNA was isolated from both the patient and his parents and processed using OGM. Genome assembly was followed by variant calling and annotation. Multiple strategies confirmed the results. The 3p deletion, which disrupted , (MIM*602431) included three copy-neutral insertions. Two came from chromosome 13; the third contained 15q21.1, including the from intron-45 onwards, thus explaining the MFS phenotype. We could not attribute the ID to a specific gene variant nor to the reshuffling of topologically associating domains (TADs). Our patient did not have vesicular reflux-2, as reported by missense alterations of (VUR2, MIM#610878), implying that reduced expression of all or some isoforms has a different effect than some of the point mutations. Indeed, the expression pattern and its role as an axon-guide suggests that its partial deletion is responsible for the patient's neurological phenotype. Conclusion: OGM testing 1) highlights copy-neutral variants that could remain invisible if no loss of heterozygosity is observed and 2) is mandatory before other molecular studies in the presence of any chromosomal rearrangement for an accurate genotype-phenotype relationship.
PubMed: 37811140
DOI: 10.3389/fgene.2023.1244983 -
Journal of Insect Science (Online) Sep 2023The domesticated silkworm, Bombyx mori Linnaeus (Lepidoptera: Bombycidae), often poses a challenge in strain identification due to similarities in morphology and genetic...
The domesticated silkworm, Bombyx mori Linnaeus (Lepidoptera: Bombycidae), often poses a challenge in strain identification due to similarities in morphology and genetic background. In South Korea, around 40 silkworm strains are classified as premium, including 5 endemic tri-molting strains: Goryeosammyeon, Sammyeonhonghoeback, Hansammyeon, Sun7ho, and Sandongsammyeon. These strains have potential for breeding programs in response to emerging industry demands, necessitating a reliable strain identification method. In this study, we established a molecular diagnosis approach for these 5 strains. We selected 2-4 single-nucleotide polymorphisms (SNPs) for each strain from whole-genome sequences of 39 strains, encompassing 37 previously studied and 2 newly added. These SNPs were utilized to construct decision trees for each endemic strain identification. The SNPs can be used to distinguish each target strain from the 38 nontarget strains by the tetra-primer amplification refractory mutation system-polymerase chain reaction, with the exception of HMS which needs the addition of PCR-restriction fragment length polymorphism method at the final step. This decision tree-based method using genomic SNPs, coupled with the 2 typing methods, produced consistent and accurate results, providing 100% accuracy. Additionally, the significant number of remaining SNPs identified in this study could be valuable for future diagnosis of the other strains.
Topics: Animals; Polymorphism, Single Nucleotide; Bombyx; Chromosome Mapping; Polymerase Chain Reaction; Republic of Korea
PubMed: 37804503
DOI: 10.1093/jisesa/iead088 -
International Journal of Clinical... Oct 2023Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in... (Review)
Review
BACKGROUND
Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in care homes. Information provided by staff working within care homes is a factor that can influence prescribing decisions in residents with BPSD.
AIM
The review aimed to capture care home staff views towards antipsychotics for residents with BPSD and separately analyse tools utilized in the studies, mapping them onto the theory of planned behaviour (TPB).
METHOD
A comprehensive literature search published in ten databases was conducted between May and July 2020 and updated in July 2021. Studies published in full with no date restriction were included and quality assessed using CROSS checklist. A thematic framework approach was applied to extract data and study tools which were then mapped onto the TPB.
RESULTS
Fourteen studies (2059 participants) were included. Findings identified four overarching themes: attitudes toward antipsychotics (e.g. antipsychotics as an appropriate strategy and effectiveness); barriers to deprescribing (e.g. lower staff education, lack of resources and time, poor medication reviews); measures implemented (e.g. nonpharmacological interventions, medication reviews); and perceived needs of staff (e.g. need for training, financial or clinical support). Identified tools addressed seven but not all components of TPB namely, behavioural, normative and control beliefs, attitude, perceived behavioural control, intention and behaviour.
CONCLUSION
The positive attitudes toward antipsychotics, the identified barriers to deprescribing and the existing tools not addressing all components of the TPB provide the impetus for further research.
Topics: Humans; Nursing Homes; Antipsychotic Agents; Dementia; Attitude of Health Personnel
PubMed: 37773304
DOI: 10.1007/s11096-023-01645-2 -
Bioinformatics (Oxford, England) Oct 2023Optical genome mapping (OGM) is a technique that extracts partial genomic information from optically imaged and linearized DNA fragments containing fluorescently labeled...
MOTIVATION
Optical genome mapping (OGM) is a technique that extracts partial genomic information from optically imaged and linearized DNA fragments containing fluorescently labeled short sequence patterns. This information can be used for various genomic analyses and applications, such as the detection of structural variations and copy-number variations, epigenomic profiling, and microbial species identification. Currently, the choice of labeled patterns is based on the available biochemical methods and is not necessarily optimized for the application.
RESULTS
In this work, we develop a model of OGM based on information theory, which enables the design of optimal labeling patterns for specific applications and target organism genomes. We validated the model through experimental OGM on human DNA and simulations on bacterial DNA. Our model predicts up to 10-fold improved accuracy by optimal choice of labeling patterns, which may guide future development of OGM biochemical labeling methods and significantly improve its accuracy and yield for applications such as epigenomic profiling and cultivation-free pathogen identification in clinical samples.
AVAILABILITY AND IMPLEMENTATION
https://github.com/yevgenin/PatternCode.
Topics: Humans; Information Theory; Software; Genome; Restriction Mapping; DNA
PubMed: 37758248
DOI: 10.1093/bioinformatics/btad601 -
GigaByte (Hong Kong, China) 2023While Bacterial Artificial Chromosomes libraries were once a key resource for the genomic community, they have been obviated, for sequencing purposes, by long-read...
While Bacterial Artificial Chromosomes libraries were once a key resource for the genomic community, they have been obviated, for sequencing purposes, by long-read technologies. Such libraries may now serve as a valuable resource for manipulating and assembling large genomic constructs. To enhance accessibility and comparison, we have developed a BAC restriction map database. Using information from the National Center for Biotechnology Information's cloneDB FTP site, we constructed a database containing the restriction maps for both uniquely placed and insert-sequenced BACs from 11 libraries covering the recognition sequences of the available restriction enzymes. Along with the database, we generated a set of Python functions to reconstruct the database and more easily access the information within. This data is valuable for researchers simply using BACs, as well as those working with larger sections of the genome in terms of synthetic genes, large-scale editing, and mapping.
PubMed: 37753479
DOI: 10.46471/gigabyte.93 -
Frontiers in Cardiovascular Medicine 2023Pregnancy predisposes to arrhythmias in females due to physiological changes in the cardiovascular system, enhanced activity of the sympathetic nervous system (SNS), and... (Review)
Review
Pregnancy predisposes to arrhythmias in females due to physiological changes in the cardiovascular system, enhanced activity of the sympathetic nervous system (SNS), and changes in the endocrine system, regardless of whether there exist cardiovascular diseases before the pregnancy. Tachyarrhythmias may present for the first time or worsen persistently during pregnancy, potentially leading to maternal heart failure and sudden death, as well as some adverse fetal outcomes such as growth restriction, distress, premature birth, and stillbirth. Radiofrequency ablation (RFA) is one of the most important therapeutic methods for tachyarrhythmias. According to the 2019 European Society of Cardiology (ESC) guidelines, RFA in pregnant women should preferably be performed without x-rays. Since the 2000s, 3D mapping technique has rapidly developed, laying the foundation for cardiac electrophysiology examination free from x-rays. Ventricular arrhythmia originating from the left coronary cusp (LCC) is not common in clinic. RFA is challenging in the treatment of this type of disease due to the anatomical feature that the opening of the left main coronary artery is localized in the LCC.
PubMed: 37745096
DOI: 10.3389/fcvm.2023.1183787 -
Frontiers in Plant Science 2023High temperatures present a formidable challenge to the cultivation of hot pepper, profoundly impacting not only vegetative growth but also leading to flower and fruit...
High temperatures present a formidable challenge to the cultivation of hot pepper, profoundly impacting not only vegetative growth but also leading to flower and fruit abscission, thereby causing a significant reduction in yield. To unravel the intricate genetic mechanisms governing heat tolerance in hot pepper, an F population was developed through the crossing of two distinct genotypes exhibiting contrasting heat tolerance characteristics: DLS-161-1 (heat tolerant) and DChBL-240 (heat susceptible). The F population, along with the parental lines, was subjected to comprehensive phenotyping encompassing diverse morphological, physiological, and biochemical heat-related traits under high temperature conditions (with maximum temperature ranging from 31 to 46.5°C and minimum temperature from 15.4 to 30.5°C). Leveraging the Illumina Nova Seq-6000 platform, Double digest restriction-site associated DNA sequencing (ddRAD-seq) was employed to generate 67.215 Gb data, with subsequent alignment of 218.93 million processed reads against the reference genome of . Subsequent variant calling and ordering resulted in 5806 polymorphic SNP markers grouped into 12 LGs. Further QTL analysis identified 64 QTLs with LOD values ranging from 2.517 to 11.170 and explained phenotypic variance ranging from 4.05 to 19.39%. Among them, 21 QTLs, explaining more than 10% phenotypic variance, were identified as major QTLs controlling 9 morphological, 3 physiological, and 2 biochemical traits. Interestingly, several QTLs governing distinct parameters were found to be colocalized, suggesting either a profound correlation between the QTLs regulating these traits or their significant genomic proximity. In addition to the QTLs, we also identified 368380 SSR loci within the identified QTL regions, dinucleotides being the most abundant type (211,381). These findings provide valuable insights into the genetics of heat tolerance in hot peppers. The identified QTLs and SSR markers offer opportunities to develop heat-tolerant varieties, ensuring better crop performance under high-temperature conditions.
PubMed: 37692444
DOI: 10.3389/fpls.2023.1232800 -
BMC Genomics Aug 2023For Asian seabass (Lates calcarifer, Bloch 1790) cultured at sea cages various aquatic pathogens, complex environmental and stress factors are considered as leading...
BACKGROUND
For Asian seabass (Lates calcarifer, Bloch 1790) cultured at sea cages various aquatic pathogens, complex environmental and stress factors are considered as leading causes of disease, causing tens of millions of dollars of annual economic losses. Over the years, we conducted farm-based challenges by exposing Asian seabass juveniles to complex natural environmental conditions. In one of these challenges, we collected a total of 1,250 fish classified as either 'sensitive' or 'robust' individuals during the 28-day observation period.
RESULTS
We constructed a high-resolution linkage map with 3,089 SNPs for Asian seabass using the double digest Restriction-site Associated DNA (ddRAD) technology and a performed a search for Quantitative Trait Loci (QTL) associated with robustness. The search detected a major genome-wide significant QTL for increased robustness in pathogen-infected marine environment on linkage group 11 (ASB_LG11; 88.9 cM to 93.6 cM) with phenotypic variation explained of 81.0%. The QTL was positioned within a > 800 kb genomic region located at the tip of chromosome ASB_LG11 with two Single Nucleotide Polymorphism markers, R1-38468 and R1-61252, located near to the two ends of the QTL. When the R1-61252 marker was validated experimentally in a different mass cross population, it showed a statistically significant association with increased robustness. The majority of thirty-six potential candidate genes located within the QTL have known functions related to innate immunity, stress response or disease. By utilizing this ddRAD-based map, we detected five mis-assemblies corresponding to four chromosomes, namely ASB_LG8, ASB_LG9, ASB_LG15 and ASB_LG20, in the current Asian seabass reference genome assembly.
CONCLUSION
According to our knowledge, the QTL associated with increased robustness is the first such finding from a tropical fish species. Depending on further validation in other stocks and populations, it might be potentially useful for selecting robust Asian seabass lines in selection programs.
Topics: Animals; Quantitative Trait Loci; Chromosome Mapping; Perciformes; Chromosomes; Genomics; Polymorphism, Single Nucleotide; Genetic Linkage
PubMed: 37558985
DOI: 10.1186/s12864-023-09513-z -
Gait & Posture Sep 2023Toe-walking is one of the most common gait deviations (due to soleus and/or gastrocnemius muscle contractures), compromising the first (heel rocker) and second (ankle...
BACKGROUND
Toe-walking is one of the most common gait deviations (due to soleus and/or gastrocnemius muscle contractures), compromising the first (heel rocker) and second (ankle rocker) of the foot during walking. The aim of this study is to evaluate the effect of emulated artificially gastrocnemius and soleus contractures on the first and second rocker during walking.
METHOD
An exoskeleton was built to emulate contractures of the bilateral gastrocnemius and soleus muscles. Ten healthy participants were recruited to walk under the following conditions: without emulated contractures or with bilateral emulated contractures at 0°,10°, 20° and 30° of plantarflexion of the soleus or gastrocnemius in order to create an artificial restriction of dorsiflexion ankle movement. A linear regression from the ankle plantar-dorsiflexion angle pattern was performed on 0-5 % of the gait cycle (first rocker) and on 12-31 % of the gait cycle (second rocker) to compute the slope of the curve. The proportion of participants with the presence of the first and second rocker was then computed. A Statistical Parametric Mapping (SPM) analysis assessed the kinematic variations among different degrees of emulated contractures.
FINDINGS
The first and second rockers are completely absent from 10° of plantarflexion emulated contracture. The data indicate there was a non-linear shift of the gait pattern of the ankle kinematics and an important shift toward plantarflexion values with the loss of the rockers.
INTERPRETATION
This study suggests that toe-walking in the experimental simulation situation is not necessarily due to a high emulated contracture level and can occur with a small emulated contracture by an adaptation choice. This study may improve interpretation of clinical gait analysis and shows that the link between the level of gastrocnemius/soleus emulated contracture and progression of toe-walking (increased plantarflexion during gait) is not linear.
Topics: Humans; Gait; Muscle, Skeletal; Walking; Contracture; Ankle Joint; Movement Disorders; Toes; Biomechanical Phenomena
PubMed: 37523808
DOI: 10.1016/j.gaitpost.2023.07.285 -
BMJ Open Jul 2023Matching-adjusted indirect comparison (MAIC) studies are a subtype of indirect comparison, which uses propensity score weighting to enhance comparability. This method...
Mapping the characteristics, concepts and methodologies of matching-adjusted indirect comparison studies assessing pharmacological therapies in oncology: a scoping review protocol.
INTRODUCTION
Matching-adjusted indirect comparison (MAIC) studies are a subtype of indirect comparison, which uses propensity score weighting to enhance comparability. This method adjusts aggregated data based on covariables from individual patient data from studies to produce population-adjusted indirect comparisons. Some national Health Technology Assessment agencies have recently received submissions containing MAIC models. However, there can be a lack of confidence in its estimates when they are poorly reported and inconsistent with other techniques. The objective of this study is to map the characteristics, concepts and methodology of MAIC studies used for pharmacological therapies in the field of oncology.
METHODS AND ANALYSIS
A scoping review methodology will be applied following the Joanna Briggs Institute framework and the results will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews. Studies that used MAIC to compare treatments in oncology conditions will be considered eligible. A systematic search will be conducted in PubMed, Embase and the Cochrane Library. No restriction of location or language will be applied. Study screening will be documented and presented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram. Data will be extracted and recorded on a predefined data form and will be presented in a tabular form accompanied by a descriptive summary.
ETHICS AND DISSEMINATION
No ethical approval is required for this study. The results of this scoping review will be disseminated through peer-reviewed publications.
Topics: Humans; Records; Academies and Institutes; Language; Medical Oncology; Mental Processes; Research Design; Systematic Reviews as Topic; Review Literature as Topic
PubMed: 37474190
DOI: 10.1136/bmjopen-2023-072156