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Journal of Medical Genetics Jan 2022Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the...
Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of , which encodes a transcription factor of the Forkhead family. Suggestive of an autoregulation effect, the disrupted sequence matches the consensus FOXG1 and Forkhead family transcription factor binding site and has been observed in previous ChIP-seq studies to be bound by Foxg1 in early mouse brain development. Future study of this specific deletion may shed light on the regulation of expression and may enhance our understanding of the mechanisms contributing to strabismus and FOXG1 syndrome.
Topics: Adolescent; Aged; Aged, 80 and over; Animals; Forkhead Transcription Factors; Genetic Linkage; High-Throughput Nucleotide Sequencing; Humans; Middle Aged; Nerve Tissue Proteins; Pedigree; Rett Syndrome; Sequence Deletion; Strabismus; Exome Sequencing; Whole Genome Sequencing; Young Adult
PubMed: 33257509
DOI: 10.1136/jmedgenet-2020-107226 -
ACS Omega Feb 2021Rapid, accurate, and low-cost detection of SARS-CoV-2 is crucial to contain the transmission of COVID-19. Here, we present a cost-effective smartphone-based device...
Rapid, accurate, and low-cost detection of SARS-CoV-2 is crucial to contain the transmission of COVID-19. Here, we present a cost-effective smartphone-based device coupled with machine learning-driven software that evaluates the fluorescence signals of the CRISPR diagnostic of SARS-CoV-2. The device consists of a three-dimensional (3D)-printed housing and low-cost optic components that allow excitation of fluorescent reporters and selective transmission of the fluorescence emission to a smartphone. Custom software equipped with a binary classification model has been developed to quantify the acquired fluorescence images and determine the presence of the virus. Our detection system has a limit of detection (LoD) of 6.25 RNA copies/μL on laboratory samples and produces a test accuracy of 95% and sensitivity of 97% on 96 nasopharyngeal swab samples with transmissible viral loads. Our quantitative fluorescence score shows a strong correlation with the quantitative reverse transcription polymerase chain reaction (RT-qPCR) Ct values, offering valuable information of the viral load and, therefore, presenting an important advantage over nonquantitative readouts.
PubMed: 33553890
DOI: 10.1021/acsomega.0c04929 -
Horticulture Research Jan 2022Free amino acids are one of the main chemical components in tea, and they contribute to the pleasant flavor, function, and quality of tea, notably the level of theanine....
Free amino acids are one of the main chemical components in tea, and they contribute to the pleasant flavor, function, and quality of tea, notably the level of theanine. Here, a high-density genetic map was constructed to characterize quantitative trait loci (QTLs) for free amino acid content. A total of 2688 polymorphic SNP markers were obtained using genotyping-by-sequencing (GBS) based on 198 individuals derived from a pseudotestcross population of "Longjing 43" × "Baijiguan", which are elite and albino tea cultivars, respectively. The 1846.32 cM high-density map with an average interval of 0.69 cM was successfully divided into 15 linkage groups (LGs) ranging from 93.41 cM to 171.28 cM. Furthermore, a total of 4 QTLs related to free amino acid content (theanine, glutamate, glutamine, aspartic acid and arginine) identified over two years were mapped to LG03, LG06, LG11 and LG14. The phenotypic variation explained by these QTLs ranged from 11.8% to 23.7%, with an LOD score from 3.56 to 7.7. Furthermore, several important amino acid metabolic pathways were enriched based on the upregulated differentially expressed genes (DEGs) among the offspring. These results will be essential for fine mapping genes involved in amino acid pathways and diversity, thereby providing a promising avenue for the genetic improvement of tea plants.
PubMed: 35040977
DOI: 10.1093/hr/uhab029 -
Horticulture Research 2022The fresh and unique flavor of cucumber fruits, mainly composed of aldehydes and alcohols, is one of its most important fruit qualities. However, little is known about...
The fresh and unique flavor of cucumber fruits, mainly composed of aldehydes and alcohols, is one of its most important fruit qualities. However, little is known about the genetic basis of aroma compounds in cucumber fruit and the related quantitative trait loci (QTLs). In this study, genomic screening of QTLs underlying aroma compounds was performed based on the genetic linkage map constructed using 1301 single-nucleotide polymorphism (SNP) markers from genotyping-by-sequencing of a recombinant inbred line (RIL) population developed from Q16 × Q24. Significant genetic variations of aroma compounds in the RIL population were observed, and a total of 28 QTLs were screened. A major QTL () related to (,)-2,6-nonadien-1-ol was detected with a markedly high LOD score (10.97 in 2020 and 3.56 in 2019) between mk190 and mk204 on chromosome 2. Genome scans identified a cluster of nine lipoxygenase genes in this region. A significant positive correlation was detected between () and (,)-2,6-nonadien-1-ol, and five amino acid variations were detected between the CsLOX08 protein sequences of the two parental lines. Based on the genome variation of CsLOX08, we developed an InDel marker. Genotyping of InDel markers was consistent with the content of (,)-2,6-nonadien-1-ol in RILs, which were also verified in nine cucumber inbred lines. The results will give breeders guidance for obtaining better flavor in cucumber.
PubMed: 36196068
DOI: 10.1093/hr/uhac151 -
Scientific Reports Jul 2021We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder and attention deficit...
We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (n = 4), genotyping by genome-wide SNP array (n = 34) and whole-genome sequencing (n = 12). We performed genome-wide linkage analysis, family-based association analysis and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score = 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4 and TRIM32, previously associated with MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.
Topics: Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Cell Cycle Proteins; Chromosomes, Human, Pair 9; Depressive Disorder, Major; Female; Genetic Linkage; Glycoproteins; Humans; Male; Nerve Tissue Proteins; Pedigree; Polymorphism, Single Nucleotide; Psychotic Disorders; Spain
PubMed: 34267256
DOI: 10.1038/s41598-021-93555-4 -
Journal of Medical Genetics Dec 2019Alexander disease, an autosomal dominant leukodystrophy, is caused by missense mutations in . Although mostly diagnosed in children, associated with severe...
BACKGROUND
Alexander disease, an autosomal dominant leukodystrophy, is caused by missense mutations in . Although mostly diagnosed in children, associated with severe leukoencephalopathy, milder adult forms also exist.
METHODS
A family affected by adult-onset spastic paraplegia underwent neurological examination and cerebral MRI. Two patients were sequenced by whole exome sequencing (WES). A candidate variant was functionally tested in an astrocytoma cell line.
RESULTS
The novel variant in (Glial Fibrillary Acidic Protein) N-terminal head domain (p.Gly18Val) cosegregated in multiple relatives (LOD score: 2.7). All patients, even those with the mildest forms, showed characteristic signal changes or atrophy in the brainstem and spinal cord MRIs, and abnormal MRS. In vitro, this variant did not cause significant protein aggregation, in contrast to most Alexander disease mutations characterised so far. However, cell area analysis showed larger size, a feature previously described in patients and mouse models.
CONCLUSION
We suggest that this variant causes variable expressivity and an attenuated phenotype of Alexander disease type II, probably associated with alternative pathogenic mechanisms, that is, astrocyte enlargement. analysis should be considered in adult-onset neurological presentations with pyramidal and bulbar symptoms, in particular when characteristic findings, such as the tadpole sign, are present in MRI. WES is a powerful tool to diagnose atypical cases.
Topics: Adolescent; Adult; Aged; Alexander Disease; Female; Glial Fibrillary Acidic Protein; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Pedigree; Phenotype; Exome Sequencing; Young Adult
PubMed: 31004048
DOI: 10.1136/jmedgenet-2018-105959 -
Frontiers in Plant Science 2022Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat ( L.). To investigate quantitative trait...
Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat ( L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00-28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as , , and , respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that and were possibly two novel loci for SC and SL. and showed pleiotropic effects on plant height and grain morphology, while showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, and for , and and for were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.
PubMed: 35677243
DOI: 10.3389/fpls.2022.882655 -
Journal of Neuroengineering and... Mar 2024Effective stroke rehabilitation requires high-dose, repetitive-task training, especially during the early recovery phase. However, the usability of upper-limb...
BACKGROUND
Effective stroke rehabilitation requires high-dose, repetitive-task training, especially during the early recovery phase. However, the usability of upper-limb rehabilitation technology in acute and subacute stroke survivors remains relatively unexplored. In this study, we introduce subacute stroke survivors to MyoGuide, a mobile training platform that employs surface electromyography (sEMG)-guided neurofeedback training that specifically targets wrist extension. Notably, the study emphasizes evaluating the platform's usability within clinical contexts.
METHODS
Seven subacute post-stroke patients (1 female, mean age 53.7 years, mean time post-stroke 58.9 days, mean duration per training session 48.9 min) and three therapists (one for eligibility screening, two for conducting training) participated in the study. Participants underwent ten days of supervised one-on-one wrist extension training with MyoGuide, which encompassed calibration, stability assessment, and dynamic tasks. All training records including the Level of Difficulty (LoD) and Stability Assessment Scores were recorded within the application. Usability was assessed through the System Usability Scale (SUS) and participants' willingness to continue home-based training was gauged through a self-developed survey post-training. Therapists also documented the daily performance of participants and the extent of support required.
RESULTS
The usability analysis yielded positive results, with a median SUS score of 82.5. Compared to the first session, participants significantly improved their performance at the final session as indicated by both the Stability Assessment Scores (p = 0.010, mean = 229.43, CI = [25.74-433.11]) and the LoD (p < 0.001; mean: 45.43, CI: [25.56-65.29]). The rate of progression differed based on the initial impairment levels of the patient. After training, participants expressed a keen interest in continuing home-based training. However, they also acknowledged challenges related to independently using the Myo armband and software.
CONCLUSIONS
This study introduces the MyoGuide training platform and demonstrates its usability in a clinical setting for stroke rehabilitation, with the assistance of a therapist. The findings support the potential of MyoGuide for wrist extension training in patients across a wide range of impairment levels. However, certain usability challenges, such as donning/doffing the armband and navigating the application, need to be addressed to enable independent MyoGuide training requiring only minimal supervision by a therapist.
Topics: Humans; Female; Middle Aged; Wrist; Stroke; Stroke Rehabilitation; Upper Extremity; Wrist Joint
PubMed: 38515192
DOI: 10.1186/s12984-024-01334-9 -
Journal of Speech, Language, and... Dec 2020Purpose Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of...
Purpose Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions These results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI. Supplemental Material https://doi.org/10.23641/asha.13203218.
Topics: Chromosome Mapping; Genetic Predisposition to Disease; Humans; Lod Score; Pedigree; Specific Language Disorder
PubMed: 33186502
DOI: 10.1044/2020_JSLHR-20-00102 -
Environment International Dec 2021Parabens are used as antimicrobial preservatives in personal care products. Few studies have dealt with adverse health outcomes, transplacental transfer, and obesogenic...
In utero exposure to parabens and early childhood BMI z-scores - Associations between placental ethyl paraben, longitudinal BMI trajectories and cord blood metabolic biomarkers.
BACKGROUND
Parabens are used as antimicrobial preservatives in personal care products. Few studies have dealt with adverse health outcomes, transplacental transfer, and obesogenic effects of prenatal exposure to parabens. We examined the association between placental paraben levels and cord blood metabolic biomarkers, considering modulating effects of maternal pre-pregnancy BMI and underlying epigenetic mechanisms, and investigated longitudinal effects of in utero paraben exposure on early childhood trajectories of BMI z-scores.
METHODS
Placental concentrations of four parabens [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 229 placentas of the ENVIRONAGE birth cohort. The association with cord blood metabolic biomarkers [glucose, insulin, γ-glutamyltransferase (GGT), high-density and low-density lipoprotein (HDL and LDL)] was analyzed in multiple regression models with two different sets of, a priori selected potential confounders, additionally stratified for different maternal BMI groups and assessed by causal mediation analysis. The association between placental paraben concentration and differential DNA methylation of CpGs annotated to GGT and longitudinal measurements of BMI z-scores were investigated with adjusted linear mixed models.
RESULTS
The geometric means of placental MeP, EtP, PrP, and BuP levels above the limit of detection (LOD) were 4.42, 1.32, 1.51, and 0.35 ng/g respectively, with only EtP showing sufficient (88%) measurements above LOD for further analyses. An interquartile ratio (IQR) increase in placental EtP was associated with an increase of 12.61 % (95% CI: 1.80 24.57) in the geometric mean of cord GGT activity, and with a decrease of -3.64 % (95% CI: -6.80 to -0.39) in the geometric mean of cord glucose. Placental EtP levels were significantly associated with hypermethylation of cg08612779 annotated to GGT7 after correcting for multiple testing (ß = 0.0017, p = 0.049). An interquartile ratio (IQR) increment in placental EtP was associated with a decrease in longitudinal BMI z-score of 0.27 points (95% CI: -0.46 to -0.088).
CONCLUSION
Prenatal EtP exposure may affect early childhood BMI. The association of placental EtP with cord blood GGT and glucose levels provides a starting point for further research on mechanisms of paraben-related metabolic processes in utero.
Topics: Biomarkers; Body Mass Index; Child, Preschool; Female; Fetal Blood; Humans; Parabens; Placenta; Pregnancy
PubMed: 34474324
DOI: 10.1016/j.envint.2021.106845