Additive and non-additive genetic variance in juvenile Sitka spruce (Picea sitchensis Bong. Carr)

Many quantitative genetic models assume that all genetic variation is additive because of a lack of data with sufficient structure and quality to determine the relative contribution of additive and non-additive variation. Here the fractions of additive (fa) and non-additive (fd) genetic variation were estimated in Sitka spruce for height, bud burst and pilodyn penetration depth. Approximately 1500 offspring were produced in each of three sib families and clonally replicated across three geographically diverse sites. Genotypes from 1525 offspring from all three families were obtained by RADseq, followed by imputation using 1630 loci segregating in all families and mapped using the newly developed linkage map of Sitka spruce. The analyses employed a new approach for estimating fa and fd, which combined all available genotypic and phenotypic data with spatial modelling for each trait and site. The consensus estimate for fa increased with age for height from 0.58 at 2 years to 0.75 at 11 years, with only small overlap in 95% support intervals (I95). The estimated fa for bud burst was 0.83 (I95=[0.78, 0.90]) and 0.84 (I95=[0.77, 0.92]) for pilodyn depth. Overall, there was no evidence of family heterogeneity for height or bud burst, or site heterogeneity for pilodyn depth, and no evidence of inbreeding depression associated with genomic homozygosity, expected if dominance variance was the major component of non-additive variance. The results offer no support for the development of sublines for crossing within the species. The models give new opportunities to assess more accurately the scale of non-additive variation

Regional variations in diffuse nitrogen losses from agriculture in the Nordic and Baltic regions

International audienceThis paper describes nitrogen losses from, and the characteristics of, 35 selected catchments (12 to 2000 ha) in the Nordic and Baltic countries. Average annual losses of N in 1994?1997 ranged from 5 to 75 kg ha-1, generally highest and characterised by significant within-country and interannual variations, in Norway and the lowest losses were observed in the Baltic countries. An important finding of the study is that the average nutrient losses varied greatly among the studied catchments. The main explanations for this variability were water runoff, fertiliser use (especially the amount of manure), soil type and erosion (including stream bank erosion). However, there were several exceptions, and it was difficult to find general relationships between the individual factors. For example, there was poor correlation between nitrogen losses and surpluses. Therefore, the results suggest that the observed variability in N losses cannot have been due solely to differences in farm management practices, although the studied catchments do include a wide range of nutrient application levels, animal densities and other relevant elements. There is considerable spatial variation in the physical properties (soil, climate, hydrology, and topography) and the agricultural management of the basins, and the interaction between and relative effects of these factors has an important impact on erosion and nutrient losses. In particular, hydrological processes may have a marked effect on N losses measured in the catchment stream water. The results indicate that significant differences in hydrological pathways (e.g. the relationship between fast- and slow-flow processes) lead to major regional differences in N inputs to surface waters and therefore also in the response to changes in field management practices. Agricultural practices such as crop rotation systems, nutrient inputs and soil conservation measures obviously play a significant role in the site-specific effects, although they cannot explain the large regional differences observed in this study. The interactions between agricultural practices and basic catchment characteristics, including hydrological processes, determine the final losses of nitrogen to surface waters, hence it is necessary to understand these interactions to manage diffuse losses of agricultural nutrients efficiently. Keywords: agriculture, catchments, diffuse sources, nitrogen, losses, Baltic, Nordi

Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

Heterogenization of Homogeneous Catalysts: the Effect of the Support

We have studied the influence of placing a soluble, homogeneous catalyst onto a solid support. We determined that such a 'heterogenized' homogeneous catalyst can have improved activity and selectivity for the asymmetric hydrogenation of enamides to amino acid derivatives. The route of heterogenization of RhDuPhos(COD){sup +} cations occurs via electrostatic interactions with anions that are capable of strong hydrogen bonding to silica surfaces. This is a novel approach to supported catalysis. Supported RhDuPhos(COD){sup +} is a recyclable, non-leaching catalyst in non-polar media. This is one of the few heterogenized catalysts that exhibits improved catalytic performance as compared to its homogeneous analog

AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells

Upon activation, B cells divide, form a germinal center, and express the activation induced deaminase (AID), an enzyme that triggers somatic hypermutation of the variable regions of immunoglobulin (Ig) loci. Recent evidence indicates that at least 25% of expressed genes in germinal center B cells are mutated or deaminated by AID. One of the most deaminated genes, c-Myc, frequently appears as a translocation partner with the Ig heavy chain gene (Igh) in mouse plasmacytomas and human Burkitt's lymphomas. This indicates that the two genes or their double-strand break ends come into close proximity at a biologically relevant frequency. However, the proximity of c-Myc and Igh has never been measured in germinal center B cells, where many such translocations are thought to occur. We hypothesized that in germinal center B cells, not only is c-Myc near Igh, but other mutating non-Ig genes are deaminated by AID because they are near Ig genes, the primary targets of AID. We tested this “collateral damage” model using 3D-fluorescence in situ hybridization (3D-FISH) to measure the distance from non-Ig genes to Ig genes in germinal center B cells. We also made mice transgenic for human MYC and measured expression and mutation of the transgenes. We found that there is no correlation between proximity to Ig genes and levels of AID targeting or gene mutation, and that c-Myc was not closer to Igh than were other non-Ig genes. In addition, the human MYC transgenes did not accumulate mutations and were not deaminated by AID. We conclude that proximity to Ig loci is unlikely to be a major determinant of AID targeting or mutation of non-Ig genes, and that the MYC transgenes are either missing important regulatory elements that allow mutation or are unable to mutate because their new nuclear position is not conducive to AID deamination

Using global team science to identify genetic parkinson's disease worldwide.

No abstract available

Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)

Correction to: npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations:Experience from the MJFF Global Genetic Parkinson's Disease Project

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.</p

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society