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Mycoscience 2021Developing high-content strains of L-ergothioneine (EGT), an antioxidant amino acid, is an important breeding target for tamogitake mushroom, var. . We constructed a...
Developing high-content strains of L-ergothioneine (EGT), an antioxidant amino acid, is an important breeding target for tamogitake mushroom, var. . We constructed a genetic linkage map based on segregation analysis of markers in 105 F1 progenies. The loci of 245 markers, including 10 AFLP markers, 195 Rad markers, 2 mating type factors, and 38 gene markers, were mapped. The map contained 12 linkage groups with a total genetic distance of 906.8 cM, and an average marker interval of 4.0 cM. The population from crossing between tester monokaryon and F1 progenies was used to characterize quantitative trait loci (QTL) for EGT content. With composite interval mapping (CIM) method, QTL of EGT content were found to be located in linkage group 10, having a Logarithm of the odds (LOD) score of 2.53 with a 10.1% contribution rate. Moreover, a single nucleotide polymorphism (SNP), A/T, was identified in a gene region of the genome in the neighborhood where the QTL peak existed. This SNP genotype was in good agreement with the EGT phenotypes of each strain in the both QTL population and wild population. Thus, this SNP would have great potential value to use the marker-assisted selection (MAS) for this mushroom with high EGT content.
PubMed: 37090022
DOI: 10.47371/mycosci.2020.11.003 -
PloS One 2020Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the...
Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.
Topics: Chromosome Mapping; Female; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Germany; Haplotypes; High-Throughput Nucleotide Sequencing; Humans; Hyperhidrosis; Male; Pedigree; Polymorphism, Single Nucleotide; Exome Sequencing
PubMed: 33378362
DOI: 10.1371/journal.pone.0244565 -
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 -
Journal of Applied Genetics Feb 2021Cytoplasmic male sterility (CMS) phenomenon is widely exploited in commercial hybrid seed production in economically important crop species, including rye, wheat, maize,...
Cytoplasmic male sterility (CMS) phenomenon is widely exploited in commercial hybrid seed production in economically important crop species, including rye, wheat, maize, rice, sorghum, cotton, sugar beets, and many vegetables. Although some commercial successes, little is known about QTLs responsible for the trait in case of triticale with sterilizing Triticum timopheevii (Tt) cytoplasm. Recombinant inbred line (RIL) F6 mapping population encompassing 182 individuals derived from the cross of individual plants representing the HT352 line and cv Borwo was employed for genetic map construction using SNP markers and identification of QTLs conferring pollen sterility in triticale with CMS Tt. The phenotypes of the F1 lines resulting from crossing of the HT352 (Tt) with HT352 (maintainer) × Borwo were determined by assessing the number of the F2 seeds per spike. A genetic map with 21 linkage groups encompasses 29,737 markers and spanned over the distance of 2549 cM. Composite (CIM) and multiple (MIM) interval mappings delivered comparable results. Single QTLs mapped to the 1A, 1B, 2A, 2R, 3B, 3R, 4B, and 5B chromosomes, whereas the 5R and 6B chromosomes shared 3 and 2 QTLs, respectively. The QTLs with the highest LOD score mapped to the 5R, 3R, 1B, and 4B chromosomes; however, the QRft-5R.3 has the highest explained variance of the trait.
Topics: Chromosome Mapping; Cytoplasm; Fertility; Genetic Linkage; Phenotype; Plant Infertility; Pollen; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Triticale; Triticum
PubMed: 33230679
DOI: 10.1007/s13353-020-00595-z -
Prognostic value of the H FPEF score in patients undergoing transcatheter aortic valve implantation.ESC Heart Failure Feb 2021The aim of this study was to assess the prognostic value of the H FPEF score in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic...
AIMS
The aim of this study was to assess the prognostic value of the H FPEF score in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) and preserved left ventricular ejection fraction (EF).
METHODS AND RESULTS
In this multicentre study, a total of 832 patients from two German high-volume centres, who received TAVI for severe AS and preserved EF (≥50%), were identified for calculation of the H FPEF score. Patients were dichotomized according to low (0-5 points; n = 570) and high (6-9 points; n = 262) H FPEF scores. Kaplan-Meier and Cox regression analyses were applied to assess the prognostic impact of the H FPEF score. We observed a decrease in stroke volume index (-2.04 mL/m /point) and mean transvalvular gradients (-1.14 mmHg/point) with increasing H FPEF score translating into a higher prevalence of paradoxical low-flow, low-gradient AS among patients with high H FPEF score. One year after TAVI, the rates of all-cause (low vs. high H FPEF score: 8.0% vs. 19.4%, P < 0.0001) and cardiovascular (CV) mortality (1.9% vs. 9.0%, P < 0.0001) as well as the rate of CV mortality or rehospitalization for congestive heart failure (6.4% vs. 23.2%, P < 0.0001) were higher in patients with high H FPEF score compared with those with low H FPEF score. After multivariable analysis, a high H FPEF score remained independently predictive of all-cause mortality [hazard ratio 1.59 (1.28-2.35), P = 0.018] and CV mortality or rehospitalization for congestive heart failure [hazard ratio 2.92 (1.65-5.15), P < 0.001]. Among the H FPEF score variables, atrial fibrillation, pulmonary hypertension, and elevated left ventricular filling pressure were the strongest outcome predictors.
CONCLUSIONS
The H FPEF score serves as an independent predictor of adverse CV and heart failure outcome among TAVI patients with preserved EF. A high H FPEF score is associated with the presence of paradoxical low-flow, low-gradient AS, the HFpEF in patients with AS. By identifying patients in advanced stages of HFpEF, the H FPEF score might be useful as a risk prediction tool in patients with preserved EF scheduled for TAVI.
Topics: Aortic Valve Stenosis; Heart Failure; Humans; Prognosis; Stroke Volume; Transcatheter Aortic Valve Replacement; Ventricular Function, Left
PubMed: 33215870
DOI: 10.1002/ehf2.13096 -
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 -
Circulation Feb 2021Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a...
BACKGROUND
Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in 5 trials across the spectrum of cardiometabolic disease.
METHODS
Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), SOLID-TIMI 52 (Stabilization of Plaques Using Darapladib), SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials were included in this analysis. A set of 32 single-nucleotide polymorphisms associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors.
RESULTS
In 51 288 subjects across the 5 trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, a higher GRS was strongly and independently associated with increased risk for ischemic stroke ( trend=0.009). In comparison with individuals in the lowest third of the GRS, individuals in the middle and top tertiles of the GRS had adjusted hazard ratios of 1.15 (95% CI, 0.98-1.36) and 1.24 (95% CI 1.05-1.45) for ischemic stroke, respectively. Stratification into subgroups revealed that the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted hazard ratio for the top versus lowest tertile of 1.27 (95% CI, 1.04-1.53), in comparison with an adjusted hazard ratio of 1.06 (95% CI, 0.81-1.41) in subjects with previous stroke. In an exploratory analysis of patients with atrial fibrillation and CHADS-VASc score of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHADS-VASc score of 3.
CONCLUSIONS
Across a broad spectrum of subjects with cardiometabolic disease, a 32-single-nucleotide polymorphism GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHADS-VASc scores, the GRS identified patients with risk comparable to those with higher CHADS-VASc scores.
Topics: Aged; Aged, 80 and over; Female; Genome-Wide Association Study; Genotyping Techniques; Humans; Ischemic Stroke; Male; Metabolic Syndrome; Risk Assessment; Risk Factors
PubMed: 33185476
DOI: 10.1161/CIRCULATIONAHA.120.051927 -
Zeitschrift Fur Kinder- Und... Nov 2020Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we...
Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we investigated a four-generation pedigree where transmission of dyslexia is consistent with an autosomal dominant inheritance pattern. We performed genome wide array-based SNP genotyping and parametric linkage analysis and sequencing analysis of protein-coding exons, exon-intron boundaries and conserved extragenic regions within the haplotype cosegregating with dyslexia in DNA from one affected and one unaffected family member. Cosegregation was confirmed by sequencing all available family members. Additionally, we analyzed 96 dyslexic individuals who had previously shown positive LOD scores on chromosome 4q28 as well as an even larger sample ( = 2591). We found a single prominent linkage interval on chromosome 4q, where sequence analysis revealed a nucleotide variant in the 3' UTR of brain expressed in the dyslexic family member that cosegregated with dyslexia. This sequence alteration might affect the binding efficiency of the IGF2BP1 RNA-binding protein and thus influence the expression level of the gene product. An analysis of 96 individuals from a cohort of dyslexic individuals revealed a second heterozygous variant in this gene, which was absent in the unaffected sister of the proband. An investigation of the region in a much larger sample further found a nominal -value of 0.0016 for verbal short-term memory (digit span) in 2,591 individuals for a neighboring SNV. After correcting for the local number of analyzed SNVs, and after taking into account linkage disequilibrium, we found this corresponds to a -value of 0.0678 for this phenotype. We describe a new locus for familial dyslexia and discuss the possibility that might play a role in the etiology of a monogenic form of dyslexia.
Topics: 3' Untranslated Regions; Chromosomes, Human, Pair 4; Dyslexia; Family Health; Humans; Lod Score; Membrane Proteins; Pedigree; Phosphoproteins; RNA-Binding Proteins
PubMed: 33172359
DOI: 10.1024/1422-4917/a000758 -
PloS One 2020The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole...
The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5' untranslated region (UTR), 152 within the 3'UTR, 2 within intergenic regions and 34 within coding sequences.
Topics: 3' Untranslated Regions; 5' Untranslated Regions; Betacoronavirus; Genetic Linkage; Genome, Viral; Linkage Disequilibrium; Lod Score; Mutation; SARS-CoV-2; Sequence Analysis, RNA; Whole Genome Sequencing
PubMed: 33152019
DOI: 10.1371/journal.pone.0241535 -
GeroScience Apr 2021The association between late-life depression (LLD) and age-related hearing loss (ARHL) was suggested by preliminary studies, but reliance on LLD subtypes may introduce...
The association between late-life depression (LLD) and age-related hearing loss (ARHL) was suggested by preliminary studies, but reliance on LLD subtypes may introduce significant bias. We examined the association between ARHL and LLD according to the age of onset (early-onset depression (EOD) and late-onset depression (LOD)). We investigated the association between ARHL and LLD diagnosed according to the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR in 1749 Italian community-dwelling older subjects from the population-based GreatAGE Study, Southern Italy. Peripheral ARHL was assessed as a pure tone average (PTA) threshold > 40 dB hearing level in the better ear- and age-related CAPD as a score of < 50% to the Synthetic Sentences Identification with Ipsilateral Competitive Message (SSI-ICM) test. LLD amounted at 10.29% of the sample, subdivided in LOD (6.21%) and EOD (4.08%). Age-related CAPD tended to be higher in LOD (28.91%) than in EOD (19.05%). After accounting for covariates, LOD was tendentially associated to age-related CAPD, but not to peripheral ARHL. This trend was confirmed by the linear models in which LOD was significantly associated to worsen SSI-ICM percentages (odds ratio 2.38, 95% confidence interval 1.32-4.30, p = 0.004), but not to PTA values. In a fully adjusted model of LOD, the effect of the association between CAPD and LOD was explained by social dysfunction. LLD was not associated to peripheral ARHL. Age-related CAPD was associated to LOD, a form of depression with cognitive dysfunction hallmark. The ARHL assessment may be an important opportunity to prevent depressive disorders in later life, particularly for LOD.
Topics: Cognitive Dysfunction; Depression; Humans; Italy; Language Development Disorders
PubMed: 33128133
DOI: 10.1007/s11357-020-00290-1