Small and large PROS1 deletions but no other types of rearrangements detected in patents with protein S deficiency

Protein S deficiency is a dominantly inherited disorder that results from mutations in the PROS] gene. Previous sequencing of the gene failed to detect mutations in eight out of 18 investigated Swedish families, whereas segregation analyses detected large deletions in three out of the eight families. The present study investigates more thoroughly for the presence of deletions but also for other types of rearrangements. FISH analysis confirmed the existence of the three previously identified large deletions, but failed to identify any other type of rearrangement among the eight analysed families. MLPA analysis of the PROS1 gene revealed two smaller deletions covering two and four exons, respectively. Thus, deletions could be found in five out of eight families where no point mutations could be found despite sequencing of the gene. Twelve additional, not previously analysed, families were subsequently analysed using MLPA. The analysis identified two smaller deletions (3 and 4 exons). Including all PS-deficient families, i.e. also the 10 families where sequencing found a causative point mutation, deletions were identified in seven out of 30 PS-deficient families. A strategy of sequencing followed by MLPA analysis in mutation-negative families identified the causative mutation in 15 out of 18 of Swedish PS-deficient families. Most deletions were different as determined by their sizes, locations and flanking haplotypes. FISH (8 families) and MLPA analysis (20 families) failed to identify other types of rearrangements

Evolution of chloroplast mononucleotide microsatellites in Arabidopsis thaliana

The level of variation and the mutation rate were investigated in an empirical study of 244 chloroplast microsatellites in 15 accessions of Arabidopsis thaliana. In contrast to SNP variation, microsatellite variation in the chloroplast was found to be common, although less common than microsatellite variation in the nucleus. No microsatellite variation was found in coding regions of the chloroplast. To evaluate different models of microsatellite evolution as possible explanations for the observed pattern of variation, the length distribution of microsatellites in the published DNA sequence of the A. thaliana chloroplast was subsequently used. By combining information from these two analyses we found that the mode of evolution of the chloroplast mononucleotide microsatellites was best described by a linear relation between repeat length and mutation rate, when the repeat lengths exceeded about 7 bp. This model can readily predict the variation observed in non-coding chloroplast DNA. It was found that the number of uninterrupted repeat units had a large impact on the level of chloroplast microsatellite variation. No other factors investigated-such as the position of a locus within the chromosome, or imperfect repeats-appeared to affect the variability of chloroplast microsatellites. By fitting the slippage models to the Genbank sequence of chromosome 1, we show that the difference between microsatellite variation in the nucleus and the chloroplast is largely due to differences in slippage rate

Replication study of genetic variants associated with chronic rhinosinusitis and nasal polyposis

Not all network applications can make do with the best-effort service of the original Internet design. Many new applications, Including multimedia and mission-critical ones, require a certain level of service from the network to operate properly. The difficulty of finding such preferential paths is compounded by the intrinsic inaccuracies of the network state information maintained by the nodes that have to make such decisions. We choose a stochastic framework to select paths for applications that want more cooperation from the network to operate satisfactorily. We represent the stochasticity of links by means of a new composite metric composed of an interval with a lower and upper bound and an associated probability. The interpretation and relevance of our metric is such that in the next decision time period the expected value of the resource is between the upper and the lower bound with the associated probability. Simple and straightforward methods of computing our composite metric are presented. An algorithm, called Augmented-Dijkstra, with the same complexity as the standard Dijkstra, provides an effective solution for statistical bandwidth guarantees. Simulation results evaluate and confirm the effectiveness of our approach. ©2006 IEEE.link_to_subscribed_fulltex

Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients

von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. This study aims to screen comprehensively for CLEC4M variants and investigate their association with type 1 VWD in the Swedish population. In order to screen for CLEC4M variants, the CLEC4M gene region was re-sequenced and the polymorphic neck region was genotyped in 106 type 1 VWD patients from unrelated type 1 VWD families. Single nucleotide variants (SNV) and variable number tandem repeat (VNTR) allele and genotype frequencies were then compared with 294 individuals from the 1000Genomes project and 436 Swedish control individuals. Re-sequencing identified a total of 42 SNVs. Rare variants showed no accumulation in type 1 VWD patients and are not thought to contribute substantially to type 1 VWD. The only missense mutation (rs2277998, NP_001138379.1:p.Asp224Asn) had a higher frequency in type 1 VWD patients than in controls (4.9%). The VNTR genotypes 57 and 67 were observed at higher frequencies than expected in type 1 VWD patients (6.4% and 6.2%) and showed an increase in patients compared with controls (7.4% and 3.1%). Strong linkage disequilibrium in the CLEC4M region makes it difficult to distinguish between the effect of the missense mutation and the VNTR genotypes. In conclusion, heterozygous VNTR genotypes 57 and 67 of CLEC4M were highly enriched and are the most likely mechanism through which CLEC4M contributes to disease in the Swedish type 1 VWD population

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 May 2009-31 July 2009

This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle, Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium alboatrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.Glenn R. Almany...Rohan Mellick...Maurizio Rossetto...et al

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 May 2009–31 July 2009

This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.This article is from Molecular Ecology Resources 9 (2009): 1460, doi:10.1111/j.1755-0998.2009.02759.x.</p