Heavy metal concentrations in various aqueous and biotic media in Finnish Integrated Monitoring catchments

Concentrations of Cd, Cu, Ni, Pb and Zn in various aqueous and biotic media in four small forested catchments located throughout Finland (61–70°N) are presented. The data has been collected (1989–96) as part of the UN-ECE Integrated Monitoring programme. Aqueous media included: bulk (open) precipitation, throughfall, stemflow, soil water, groundwater, and lake and stream waters. The biotic media included: moss (Pleurozium schreberi), needles (Pinus sylvestris), litterfall, humus layer, red wood ants (Formica aquilonia and F. lugubris), and common shrew (Sorex areneus) liver. In comparison to temperate ecosystems, the concentrations of each metal in all media were low. Levels and bioaccumulation of Cu and Zn were clearly affected by their role as micro-nutrients and, in the case of Zn at one of the catchments, by local lithological sources. Humus layer and surface water 95th percentile concentration values were below lowest effect values. Concentrations of Pb have significantly declined over the study period

Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe

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Swedish population substructure revealed by genome-wide single nucleotide polymorphism data

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High-resolution SNP array analysis of patients with developmental disorder and normal array CGH result (vol 13, 84, 2012)

Peer reviewe

Dominant Distal Myopathy 3 (MPD3) Caused by a Deletion in the HNRNPA1 Gene

Background and Objectives To determine the genetic cause of the disease in the previously reported family with adult-onset autosomal dominant distal myopathy (myopathy, distal, 3; MPD3). Methods Continued clinical evaluation including muscle MRI and muscle pathology. A linkage analysis with single nucleotide polymorphism arrays and genome sequencing were used to identify the genetic defect, which was verified by Sanger sequencing. RNA sequencing was used to investigate the transcriptional effects of the identified genetic defect. Results Small hand muscles (intrinsic, thenar, and hypothenar) were first involved with spread to the lower legs and later proximal muscles. Dystrophic changes with rimmed vacuoles and cytoplasmic inclusions were observed in muscle biopsies at advanced stage. A single nucleotide polymorphism array confirmed the previous microsatellite-based linkage to 8p22-q11 and 12q13-q22. Genome sequencing of three affected family members combined with structural variant calling revealed a small heterozygous deletion of 160 base pairs spanning the second last exon 10 of the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) gene, which is in the linked region on chromosome 12. Segregation of the mutation with the disease was confirmed by Sanger sequencing. RNA sequencing showed that the mutant allele produces a shorter mutant mRNA transcript compared with the wild-type allele Immunofluorescence studies on muscle biopsies revealed small p62 and larger TDP-43 inclusions. Discussion A small exon 10 deletion in the gene HNRNPA1 was identified as the cause of MPD3 in this family. The new HNRNPA1-related phenotype, upper limb presenting distal myopathy, was thus confirmed, and the family displays the complexities of gene identification.Peer reviewe

Development of a single tube 640-plex genotyping method for detection of nucleic acid variations on microarrays

Detection of DNA sequence variation is critical to biomedical applications, including disease genetic identification, diagnosis and treatment, drug discovery and forensic analysis. Here, we describe an arrayed primer extension-based genotyping method (APEX-2) that allows multiplex (640-plex) DNA amplification and detection of single nucleotide polymorphisms (SNPs) and mutations on microarrays via four-color single-base primer extension. The founding principle of APEX-2 multiplex PCR requires two oligonucleotides per SNP/mutation to generate amplicons containing the position of interest. The same oligonucleotides are then subsequently used as immobilized single-base extension primers on a microarray. The method described here is ideal for SNP or mutation detection analysis, molecular diagnostics and forensic analysis. This robust genetic test has minimal requirements: two primers, two spots on the microarray and a low cost four-color detection system for the targeted site; and provides an advantageous alternative to high-density platforms and low-density detection systems

Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions

Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. In our study all patients presented with highly similar clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance.Peer reviewe

High-resolution SNP array analysis of patients with developmental disorder and normal array CGH results

Erratum to: high-resolution SNP array analysis of patients with developmental disorder and normal array CGH result BMC Medical Genetics 2014, 15:124 10.1186/s12881-014-0124-3Peer reviewe

Scientific Opinion on the safety and efficacy of iron compounds (E1) as feed additives for all species: Ferrous sulphate monohydrate based on a dossier submitted by Kronos International, Inc.

Ferrous sulphate monohydrate is safe when supplied up to a maximum iron content per kilogram complete feedingstuff of 450 mg for bovines and poultry, 500 mg for ovines, 600 mg for pets, and 750 mg for other species/categories, except horses and fish; for piglets up to one week before weaning a maximum of 250 mg Fe/day is considered safe. Because of insufficient data on horses and fish, as a provisional measure, the current value (750 mg Fe/kg) could be maintained. The values for total dietary iron for pigs, ovines, horses, fish and other species/categories (except poultry, bovines and pets) are in line with those currently authorised. Iron from ferrous sulphate monohydrate is unlikely to modify the iron concentration in edible tissues and products of animal origin. Consumer exposure in the EU is not associated with a risk of excess iron intake to the general population. Therefore, the FEEDAP Panel does not foresee any concern for consumer safety resulting from the use of ferrous sulphate monohydrate in animal nutrition, provided that the maximum iron content in complete feedingstuffs is respected. Ferrous sulphate monohydrate is irritant and corrosive to the skin, eyes and respiratory tract. The additive contains up to 109 mg Ni/kg. Nickel is a dermal and respiratory sensitiser, and inhalation may cause lung cancer. Thus, handling the additive poses a risk to the user/worker. Considering the high concentration of iron and sulphur in soil and water, the supplementation of feed with the additive is not expected to pose an environmental risk. Ferrous sulphate monohydrate is an effective iron source for all animal species and categories. The FEEDAP Panel recommends that the currently authorised maximum iron content in complete feed be reduced for bovines and poultry from 750 to 450 mg Fe/kg, and for pets from 1250 to 600 mg Fe/kg