Population genomics of selectively neutral genetic structure and herbicide resistance in UK populations of Alopecurus myosuroides

BACKGROUND Alopecurus myosuroides (blackgrass) is a major weed in Europe with known resistance to multiple herbicide modes of action. In the UK, there is evidence that blackgrass has undergone a range expansion. In this paper, genotyping‐by‐sequencing and population‐level herbicide resistance phenotypes are used to explore spatial patterns of selectively neutral genetic variation and resistance. We also perform a preliminary genome‐wide association study and genomic prediction analysis to evaluate the potential of these approaches for investigating non‐target site herbicide resistance. RESULTS Blackgrass was collected from 47 fields across the British Isles and up to eight plants per field population (N = 369) were genotyped by RAD‐sequencing. 20,426 polymorphic loci were identified and used for population genetic analyses. Phenotypic assays revealed significant variation in herbicide resistance between populations. Population structure was weak (FST = 0.024‐0.048), but spatial patterns were consistent with an ongoing westward and northward range expansion. We detected strong and consistent Wahlund effects (FIS = 0.30). There were no spatial patterns of herbicide resistance or evidence for confounding with population structure. Using a combination of population‐level GWAS and genomic prediction we found that the top 20, 200, and 2,000 GWAS loci had higher predictive abilities for fenoxaprop resistance compared to all markers. CONCLUSION There is likely extensive human‐mediated gene flow between field populations of the weed, blackgrass at a national scale. The lack of confounding of adaptive and neutral genetic variation can enable future, more extensive GWAS analyses to identify the genetic architecture of evolved herbicide resistance

THORACOSCOPY - DIAGNOSTIC AND THERAPEUTIC OPPORTUNITIES IN SURGICAL CHEST DISEASES

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WAIS-III and WMS-III performance in chronic Lyme disease

There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects

UPON THE ETIOLOGICAL TREATMENT OF BACTERIAL NONGONOCOCCAL URETHRITIS

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Functional QTL mapping and genomic prediction of canopy height in wheat measured using a robotic field phenotyping platform

Genetic studies increasingly rely on high-throughput phenotyping, but the resulting longitudinal data pose analytical challenges. We used canopy height data from an automated field phenotyping platform to compare several approaches to scanning for quantitative trait loci (QTLs) and performing genomic prediction in a wheat recombinant inbred line mapping population based on up to 26 sampled time points (TPs). We detected four persistent QTLs (i.e. expressed for most of the growing season), with both empirical and simulation analyses demonstrating superior statistical power of detecting such QTLs through functional mapping approaches compared with conventional individual TP analyses. In contrast, even very simple individual TP approaches (e.g. interval mapping) had superior detection power for transient QTLs (i.e. expressed during very short periods). Using spline-smoothed phenotypic data resulted in improved genomic predictive abilities (5–8% higher than individual TP prediction), while the effect of including significant QTLs in prediction models was relatively minor (<1–4% improvement). Finally, although QTL detection power and predictive ability generally increased with the number of TPs analysed, gains beyond five or 10 TPs chosen based on phenological information had little practical significance. These results will inform the development of an integrated, semi-automated analytical pipeline, which will be more broadly applicable to similar data sets in wheat and other crops

Improving disease resistance in mungbean - A combined genetic and biotechnological approach

Pulses are edible grains (seeds) of leguminous crops and are a main source of non-meat protein in the diet for approximately 1/3 of the Indian population. Pulses are also rich in dietary fibre, vitamins, and minerals. Mungbean is one the most important pulse crops grown and consumed in India with demand for this pulse significantly exceeding production forcing India to import mungbean from other countries. Although high yielding mungbean varieties are available, at the farm gate often only low yields are achieved largely due to the fungal diseases such as Cercospora leaf spot caused by Cercospora canescens and powdery mildew caused by Erysiphe polygoni. In collaboration with partners in India, we are pursuing an integrated approach to gain a better understanding of these economically damaging diseases and to aid development of disease resistant varieties through conventional marker assisted breeding and also by utilising emerging biotechnology tools such as RNAi and genome editing. This involves extensive phenotyping and genotyping by sequencing followed by Genome-wide association studies (GWAS) of fungal isolates sampled from all main mungbean growing states in India as well as diverse mungbean germplasm accessions and targeted mapping populations. This will allow us to pinpoint the regions of the DNA that contribute for pathogenicity and for disease resistance of the pathogens and the plant, respectively. In parallel, we will assess potential of CRISPR/Cas9 and host-induced gene silencing (HIGS) as more rapid biotechnology solutions for introducing broad spectrum disease resistance into elite mungbean varieties. Growing disease resistant varieties will allow Indian farmers to produce a more stable and improved mungbean yield, thus contributing to India’s agricultural environmental and economic sustainability and directly improving welfare for the poorest in India by improving food security

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy

Background: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. Methods: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12—specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. Results: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. Conclusion: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed

Genome-wide association studies and prediction of 17 traits related to phenology, biomass and cell wall composition in the energy grass Miscanthus sinensis

Increasing demands for food and energy require a step change in the effectiveness, speed and flexibility of crop breeding. Therefore, the aim of this study was to assess the potential of genome-wide association studies (GWASs) and genomic selection (i.e. phenotype prediction from a genome-wide set of markers) to guide fundamental plant science and to accelerate breeding in the energy grass Miscanthus. We generated over 100 000 single-nucleotide variants (SNVs) by sequencing restriction site-associated DNA (RAD) tags in 138 Micanthus sinensis genotypes, and related SNVs to phenotypic data for 17 traits measured in a field trial. Confounding by population structure and relatedness was severe in naïve GWAS analyses, but mixed-linear models robustly controlled for these effects and allowed us to detect multiple associations that reached genome-wide significance. Genome-wide prediction accuracies tended to be moderate to high (average of 0.57), but varied dramatically across traits. As expected, predictive abilities increased linearly with the size of the mapping population, but reached a plateau when the number of markers used for prediction exceeded 10 000–20 000, and tended to decline, but remain significant, when cross-validations were performed across subpopulations. Our results suggest that the immediate implementation of genomic selection in Miscanthus breeding programs may be feasible

Decreased levels of BAG3 in a family with a rare variant and in idiopathic dilated cardiomyopathy.

The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy