Garrison, J. | Search bioRxiv

bioRxiv2021

A role for worm cutl-24 in background- and parent-of-origin-dependent ER stress resistance

Organisms in the wild can acquire disease- and stress-resistance traits that outstrip the programs endogenous to humans. Finding the molecular basis of such natural resistance characters is a key goal of evolutionary genetics. Standard statistical-genetic methods toward this end can perform poorly in organismal systems that lack high rates of meiotic recombination, like Caenorhabditis worms. Here we discovered unique ER stress resistance in a wild Kenyan C. elegans isolate, which in inter-strain crosses was passed by hermaphrodite mothers to hybrid offspring. We developed an unbiased version of the reciprocal hemizygosity test, RH-seq, to explore the genetics of this parent-of-origin-dependent phenotype. Among top-scoring gene candidates from a partial-coverage RH-seq screen, we focused on the neuronally-expressed, cuticlin-like gene cutl-24 for validation. In gene disruption and controlled crossing experiments, we found that cutl-24 was required in Kenyan hermaphrodite mothers for ER stress tolerance in their inter-strain hybrid offspring; cutl-24 was also a contributor to the trait in purebred backgrounds. These data establish the Kenyan strain allele of cutl-24 as a determinant of a natural stress-resistant state, and they set a precedent for the dissection of natural trait diversity in invertebrate animals without the need for a panel of meiotic recombinants.

genetics↗

bioRxiv2018

Paracingulate sulcus morphology and hallucinations in clinical and non-clinical groups

Hallucinations are a characteristic symptom of psychotic mental health conditions that are also experienced by many individuals without a clinical diagnosis. Research has linked the experience of hallucinations in schizophrenia to differences in the length of the paracingulate sulcus (PCS), a structure in the medial prefrontal cortex of the brain which has previously been associated with the ability to differentiate perceived and imagined information. We investigated whether this notion of a specific morphological basis for hallucinations in the paracingulate cortex extends to individuals without a clinical diagnosis by testing the hypothesis that non-clinical individuals with hallucinations have shorter PCS than non-clinical individuals without hallucinations. Structural MRI scans were examined from three demographically matched groups of individuals: 50 patients with psychotic diagnoses who experienced auditory verbal hallucinations, 50 non-clinical individuals with auditory verbal hallucinations, and 50 healthy control subjects with no life-time history of hallucinations. Measurements of paracingulate sulcal length were compared between the groups and the results verified using automated data-driven gyrification analyses. Patients with hallucinations had shorter PCS than both healthy controls and non-clinical individuals with hallucinations, with no difference between non-clinical individuals with hallucinations and healthy controls. These findings suggest that the association of shorter PCS length with hallucinations is specific to patients with a psychotic disorder. This presents challenges for continuum models of psychosis and suggests possible differences in the mechanisms underlying hallucinations in clinical and non-clinical groups.

neuroscience↗