Animals encounter stressful situations multiple times throughout their lives and often successfully cope with them. Individuals vary in the nature and intensity of their behavioral and physiological response to stressors, often representing correlated and qualitatively distinct coping styles (e.g., proactive and reactive). These alternative coping styles are ways an animal can overcome a variety of stressful situations, which ultimately can have important fitness consequences. Here we use zebrafish (Danio rerio) recently wild-derived and selectively bred for amount of stationary behavior (High and Low lines) and a classic domesticated strain (AB) to document the utility of these zebrafish strains in understanding coping mechanisms. The Low Stationary Behavior (LSB) line of zebrafish displayed significantly lower stress and anxiety-related behaviors than the High Stationary Behavior (HSB) across six stress and anxiety-related behavioral assays. In some assays, we observed strain differences in behavior within three minutes of the start of the trial. Males also showed reduced levels of anxiety-related behaviors relative to females in two assays. Comparing wild-derived and domesticated strains, the AB line displayed significantly lower levels of anxietyrelated behavior in half of the assays. This study demonstrates that our selectively bred lines from wild-caught zebrafish (HSB, LSB) exhibit consistent and divergent behavioral stress responses across multiple distinct assays. Hence these lines may prove useful in understanding the proximate and ultimate mechanisms of coping with stress and anxiety.

ObjectiveTo evaluate the diagnostic yield and workflow of genome-scale sequencing in patients with neuromuscular disorders (NMDs).MethodsWe performed exome sequencing in 93 undiagnosed patients with various NMDs for whom a molecular diagnosis was not yet established. Variants on both targeted and broad diagnostic gene lists were identified. Prior diagnostic tests were extracted from the patient's medical record to evaluate the use of exome sequencing in the context of their prior diagnostic workup.ResultsThe overall diagnostic yield of exome sequencing in our cohort was 12.9%, with one or more pathogenic or likely pathogenic variants identified in a causative gene associated with the patient's disorder. Targeted gene lists had the same diagnostic yield as a broad NMD gene list in patients with clear neuropathy or myopathy phenotypes, but evaluation of a broader set of disease genes was needed for patients with complex NMD phenotypes. Most patients with NMD had undergone prior testing, but only 10/16 (63%) of these procedures, such as muscle biopsy, were informative in pointing to a final molecular diagnosis.ConclusionsGenome-scale sequencing or analysis of a panel of relevant genes used early in the evaluation of patients with NMDs can provide or clarify a diagnosis and minimize invasive testing in many cases.