Genome-Wide Analysis in German Shepherd Dogs Reveals Association of a Locus on CFA 27 with Atopic Dermatitis

Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1×10⁻⁵) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n _cases = 91, n _controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0×10⁻⁹), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (p_raw = 3.1×10⁻⁷, p_genome = 0.03). The total associated region was defined as a ∼1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ∼209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.     

Insights into FlaI Functions in Archaeal Motor Assembly and Motility from Structures,Conformations, and Genetics

1. Download : Download high-res image (278KB)
2. Download : Download full-size image

Highlights? Cross-subunit interface forms building block for transmission of ATPase force ? Structures and mutants reveal functional components for assembly and motility ? The directionality of movement explains FlaI activities and GspE differences ? The phosphate released by ATP hydrolysis triggers subunit rearrangements     

The carbon count of 2000 years of rice cultivation

More than 50% of the world's population feeds on rice. Soils used for rice production are mostly managed under submerged conditions (paddy soils). This management, which favors carbon sequestration, potentially decouples surface from subsurface carbon cycling. The objective of this study was to elucidate the long‐term rates of carbon accrual in surface and subsurface soil horizons relative to those of soils under nonpaddy management. We assessed changes in total soil organic as well as of inorganic carbon stocks along a 2000‐year chronosequence of soils under paddy and adjacent nonpaddy management in the Yangtze delta, China. The initial organic carbon accumulation phase lasts much longer and is more intensive than previously assumed, e.g., by the Intergovernmental Panel on Climate Change (IPCC). Paddy topsoils accumulated 170–178 kg organic carbon ha^?1 a^?1 in the first 300 years; subsoils lost 29–84 kg organic carbon ha^?1 a^?1 during this period of time. Subsoil carbon losses were largest during the first 50 years after land embankment and again large beyond 700 years of cultivation, due to inorganic carbonate weathering and the lack of organic carbon replenishment. Carbon losses in subsoils may therefore offset soil carbon gains or losses in the surface soils. We strongly recommend including subsoils into global carbon accounting schemes, particularly for paddy fields.     

Effect of an overproduction of accessory Gvp proteins on gas vesicle formation in Haloferax volcanii

Gas vesicle formation in haloarchaea requires the expression of the p-vac region consisting of 14 genes, gvpACNO and gvpDEFGHIJKLM. Expression of gvpFGHIJKLM leads to essential accessory proteins formed in minor amounts. An overexpression of gvpG, gvpH or gvpM in addition to p-vac inhibited gas vesicle formation, whereas large amounts of all other Gvp proteins did not disturb the synthesis. The unbalanced expression and in particular an aggregation of the overproduced Gvp with other accessory Gvp derived from p-vac could be a reason for the inhibition. Western analyses demonstrated that the hydrophobic GvpM (and GvpJ) indeed form multimers. Fluorescent dots of GvpM–GFP were seen in cells in vivo underlining an aggregation of GvpM. In search for proteins neutralizing the inhibitory effect in case of GvpM, p-vac +pGM^ex, +pHM^ex, +pJM^ex, and +pLM^ex transformants were constructed. The inhibitory effect of GvpM on gas vesicle formation was suppressed by GvpH, GvpJ or GvpL, but not by GvpG. Western analyses demonstrated that pHM^ex and pJM^ex transformants contained additional larger protein bands when probed with an antiserum raised against GvpH or GvpJ, implying interactions. The balanced amount of GvpM–GvpH and GvpM–GvpJ appears to be important during gas vesicle genesis.     

Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes

The transition of microtubules (MTs) from an assembled to a disassembled state plays an essential role in several cellular functions. While MT dynamics are often linked to those of actin filaments, little is known about whether intermediate filaments (IFs) have an influence on MT dynamics. We show here that plectin 1c (P1c), one of the multiple isoforms of the IF-associated cytolinker protein plectin, acts as an MT destabilizer. We found that MTs in P1c-deficient (P1c^−/−) keratinocytes are more resistant toward nocodazole-induced disassembly and display increased acetylation. In addition, live imaging of MTs in P1c^−/−, as well as in plectin-null, cells revealed decreased MT dynamics. Increased MT stability due to P1c deficiency led to changes in cell shape, increased velocity but loss of directionality of migration, smaller-sized focal adhesions, higher glucose uptake, and mitotic spindle aberrations combined with reduced growth rates of cells. On the basis of ex vivo and in vitro experimental approaches, we suggest a mechanism for MT destabilization in which isoform-specific binding of P1c to MTs antagonizes the MT-stabilizing and assembly-promoting function of MT-associated proteins through an inhibitory function exerted by plectin''s SH3 domain. Our results open new perspectives on cytolinker-coordinated IF-MT interaction and its physiological significance.     

The Tarenaya hassleriana Genome Provides Insight into Reproductive Trait and Genome Evolution of Crucifers

The Brassicaceae, including Arabidopsis thaliana and Brassica crops, is unmatched among plants in its wealth of genomic and functional molecular data and has long served as a model for understanding gene, genome, and trait evolution. However, genome information from a phylogenetic outgroup that is essential for inferring directionality of evolutionary change has been lacking. We therefore sequenced the genome of the spider flower (Tarenaya hassleriana) from the Brassicaceae sister family, the Cleomaceae. By comparative analysis of the two lineages, we show that genome evolution following ancient polyploidy and gene duplication events affect reproductively important traits. We found an ancient genome triplication in Tarenaya (Th-α) that is independent of the Brassicaceae-specific duplication (At-α) and nested Brassica (Br-α) triplication. To showcase the potential of sister lineage genome analysis, we investigated the state of floral developmental genes and show Brassica retains twice as many floral MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR) genes as Tarenaya that likely contribute to morphological diversity in Brassica. We also performed synteny analysis of gene families that confer self-incompatibility in Brassicaceae and found that the critical SERINE RECEPTOR KINASE receptor gene is derived from a lineage-specific tandem duplication. The T. hassleriana genome will facilitate future research toward elucidating the evolutionary history of Brassicaceae genomes.     

The role of the Fanconi anemia network in the response to DNA replication stress

Fanconi anemia is a genetically heterogeneous disorder associated with chromosome instability and a highly elevated risk for developing cancer. The mutated genes encode proteins involved in the cellular response to DNA replication stress. Fanconi anemia proteins are extensively connected with DNA caretaker proteins, and appear to function as a hub for the coordination of DNA repair with DNA replication and cell cycle progression. At a molecular level, however, the raison d’être of Fanconi anemia proteins still remains largely elusive. The thirteen Fanconi anemia proteins identified to date have not been embraced into a single and defined biological process. To help put the Fanconi anemia puzzle into perspective, we begin this review with a summary of the strategies employed by prokaryotes and eukaryotes to tolerate obstacles to the progression of replication forks. We then summarize what we know about Fanconi anemia with an emphasis on biochemical aspects, and discuss how the Fanconi anemia network, a late acquisition in evolution, may function to permit the faithful and complete duplication of our very large vertebrate chromosomes.     

Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B

Background

Canine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible.

Results

Through genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors.

Conclusions

Mapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease.     

Non-linear effects of pesticide application on biodiversity-driven ecosystem services and disservices in a cacao agroecosystem: A modeling study

Growing concerns have been raised regarding the effects of disturbance due to agricultural practices on associate biodiversity and on the ecosystem services that biodiversity provides. Surprisingly little is known about the effects of such disturbances on complex agroecosystems with multiple interacting species. The aim of this study was to assess the effects of management by pesticide spraying on the productive outputs and the ecological functioning of a cacao agroecosystem. We built a mechanistic dynamic model including the dynamics of the crop, a pest (Cacao Pod Borer, Conopomorpha cramerella) and two beneficial insects: a hymenopteran egg–parasitoid and a ceratopogonid pollinator. Using this model, we tested the effects of a range of pesticide types characterized by their impacts on both the Cacao Pod Borer and the beneficial insects. Our results showed that yield strongly varies according to both pesticide type and timing of pesticide application. The type of pesticide had a strong influence on the flexibility of management. No simple spraying decision rule led to maximal yields for all types of pesticide. Although optimal spraying strategies differed with the type of pesticide used, they all showed a similar pattern, i.e. they limited and postponed the Cacao Pod Borer population peak while limiting the negative impacts on beneficial organisms. The results highlight the non-trivial effects of pesticide application in complex agroecosystems where associated biodiversity provides both ecosystem services and disservices. They illustrate the critical importance of providing good information to farmers on pesticide management because the use of pesticides can have a negative effect on production by decreasing ecosystem services such as pollination.