Functional Variants Associated With CMPK2 and in ASB16 Influence Bovine Digital Dermatitis.

Bovine digital dermatitis (BDD) is an infectious disease of the hoof in cattle with multifactorial etiology and a polygenic influence on susceptibility. With our study, we identified genomic regions with the impact on occurrence and development of BDD. We used 5,040 genotyped animals with phenotype information based on the M-stage system for genome-wide association. Significant associations for single-nucleotide polymorphisms were found near genes CMPK2 (chromosome 11) and ASB16 (chromosome 19) both being implicated in immunological processes. A sequence analysis of the chromosomal regions revealed rs208894039 and rs109521151 polymorphisms as having significant influence on susceptibility to the disease. Specific genotypes were significantly more likely to be affected by BDD and developed chronic lesions. Our study provides an insight into the genomic background for a genetic predisposition related to the pathogenesis of BDD. Results might be implemented in cattle-breeding programs and could pave the way for the establishment of a BDD prescreening test.

Synapsin determines memory strength after punishment- and relief-learning.

Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: "negative" memories for stimuli preceding them and "positive" memories for stimuli experienced at the moment of "relief." Such punishment memory and relief memory are found in insects, rats, and man. For example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock training ("forward conditioning" of the odor), whereas after shock-odor training ("backward conditioning" of the odor) they approach it. Do these timing-dependent associative processes share molecular determinants? We focus on the role of Synapsin, a conserved presynaptic phosphoprotein regulating the balance between the reserve pool and the readily releasable pool of synaptic vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor faculties unaffected. In contrast, both punishment memory and relief memory scores are reduced. These defects reflect a true lessening of associative memory strength, as distortions in nonassociative processing (e.g., susceptibility to handling, adaptation, habituation, sensitization), discrimination ability, and changes in the time course of coincidence detection can be ruled out as alternative explanations. Reductions in punishment- and relief-memory strength are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by acutely restoring Synapsin and by locally restoring it in the mushroom bodies of mutant flies. Thus, both punishment memory and relief memory require the Synapsin protein and in this sense share genetic and molecular determinants. We note that corresponding molecular commonalities between punishment memory and relief memory in humans would constrain pharmacological attempts to selectively interfere with excessive associative punishment memories, e.g., after traumatic experiences.