Biology subjects

Bernier, R.

Publications and source records attributed to Bernier, R..

4 recordsLinked to original sources

bioRxiv2025

Altered aperiodic EEG spectral power during speech perception task is associated with verbal communication in youths with Autism Spectrum Disorder

Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairment, but its neural mechanisms are not well known. Excitation (E) / inhibition (I) imbalance is considered as a key neurobiological mechanism of ASD, and several electroencephalography (EEG)-based E/I balance metrics have been proposed in the previous studies. The goal of the present research was to focus on these metrics abstracted from the speech perception task to investigate their relation to language/communication in autistic youths. We used a high-density 128-channel EEG to register neural responses during speech perception task in the sex- and age-matched groups of youths with ASD (N = 162) and typically developing (TD) controls (N = 144), aged 7-18 years old. The results revealed alterations in the E/I measures in the ASD group, pointing to a higher level of excitation or neural noise in the cortex as well as broadband reduction of spectral power during speech perception. A greater neural noise reflected in the reduction of aperiodic exponent and offset was associated with lower verbal communication skills in youths with ASD. The findings suggested that the higher noisiness in the cortical systems may be a relevant marker to monitor in relation to language/communication in ASD.

neuroscience↗

bioRxiv2020

Stochasticity explains differences in the number of de novo mutations between families

The number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a significant family-specific contribution. This result was corroborated by comparing DNMs of 1669 siblings to those of age-matched unrelated offspring. In addition, by modeling DNM data from 1714 multi-offspring families we estimated that the family specific contribution explains approximately 5.2% of the variation in DNM number. Furthermore, we found no significant difference between the observed number of DNMs and those based on a stochastic Poisson process. We conclude that a family-specific contribution to DNMs is small and that stochasticity explains a large proportion of variation in DNM counts.

genomics↗

bioRxiv2018

Integrative cross-species analyses identify deficits in habituation learning as a widely affected mechanism in Autism

BackgroundAlthough habituation is one of the most ancient and fundamental forms of learning, its regulators and relevance for human disease are poorly understood.\n\nMethodsWe manipulated the orthologs of 286 genes implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype-phenotype annotations, gene ontologies and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits.\n\nResultsWe identified more than 100 genes required for habituation learning. For the vast majority of these, 93 genes, a role in habituation learning was previously unknown. These genes characterize ID disorders with overgrowth/macrocephaly and comorbid ASD. Moreover, ASD individuals from the Simons Simplex Collection carrying disruptive de novo mutations in these genes exhibit increased rates of specific aberrant behaviors including stereotypic speech, hyperactivity and irritability. At the molecular level, ID genes required for normal habituation are enriched in synaptic function and converge on Ras-MAPK signaling. Both increased Ras-MAPK signaling in GABAergic and decreased Ras-MAPK signaling in cholinergic neurons specifically inhibit the adaptive habituation response.\n\nConclusionsOur work demonstrates the relevance of habituation learning to autism, identifies an unprecedented number of novel habituation players, supports an emerging role for inhibitory neurons in habituation and reveals an opposing, circuit-level-based mechanism for Ras-MAPK signaling. This establishes habituation as a possible, widely applicable target for pharmacologic intervention in ID/ASD.

neuroscience↗

bioRxiv2016

Exonic somatic mutations contribute risk for autism spectrum disorder

Genetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Somatic mosaic mutations (SMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. Here, we systematically evaluate SMMs by leveraging whole-exome sequencing (WES) data on a large family-based ASD cohort, the Simons Simplex Collection (SSC). We find evidence that ~10% of previously published de novo mutations are potentially SMMs. When using a custom somatic calling pipeline, we recalled all SSC WES data. We validated high and low confidence mutation predictions for a subset of families with single molecule molecular inversion probes. With these validation data, we iteratively developed a high confidence calling approach integrating logistic regression modeling and additional heuristics and applied it to the full cohort. Surprisingly, we found evidence of significant synonymous SMM burden in probands, with mutations more likely to be close to splicing sites. Overall, we observe no strong evidence of missense SMM burden. However, we do observe nominally significant signal for missense SMMs in those families without germline mutations, which strengthens specifically in genes intolerant to mutations. In contrast to missense germline mutations, missense SMMs show potential enrichment for chromatin modifiers. We observe 7-10% of parental mosaics are transmitted germline to a child as occult de novo mutations, which has important implications for recurrence risk for families and potential subclinical ASD features. Finally, we find SMMs in previously implicated high-confidence ASD risk genes, including CHD2, CTNNB1, KMT2C, SYNGAP1, and RELN, further suggesting that this class of mutations contribute to population risk.

genetics↗