Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B

Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia. Method comparison showed that capillary electrophoresis of long-range PCR amplification products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, − 2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, − 27.66 to 40.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92 to 1.04]; intercept: 10.62 [95% CI, − 7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, − 41.93 to 39.15]). Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. We also identified 9 French patients (9/53; 17%) and 2 of their relatives who carried an FGF14 (GAA)≥250 expansion. This novel strategy reliably detected and sized FGF14 GAA expansions, and compared favorably to long-read sequencing

Cannibalism in spiderlings is not only about starvation

International audienceMany species show a transient group life, and dispersal often coincides with the onset of agonistic behaviors. Changes in the nature of interactions among conspecifics can rely on a variation in the production of communication cues and/or on a switch in the processing of social information. The relative contribution of each process on the initiation of aggression still remains to be investigated. Spiders constitute relevant models to address this issue since all solitary species undergo a transient gregarious phase prior dispersal. In this study, we developed a combination of behavioral and physiological assays to examine the mechanisms accompanying the onset of agonistic interactions in spiderlings of the solitary species Agelena labyrinthica. Juveniles of different developmental stages were supplied with diets differing in prey availability. We showed that unfed spiderlings never molted, retained their cuticular lipid signature, and did not behave aggressively. This contrasted with fed individuals that molted, changed their cuticular profiles, and displayed agonistic interactions and cannibalism. We demonstrated that depletion in lipid stores was not sufficient to elicit aggression or cannibalism. Our analysis also revealed that major shifts in cuticular profiles only occurred after the first molt outside the cocoon. The lack of agonistic interactions in unfed spiderlings suggests an absence of behavioral plasticity in response to food shortage at the earliest developmental stages. We propose that the initiation of aggression relies more on a shift in the production of cuticular cues accompanying molting rather than on changes in information processing depending on the physiological state of individuals