Project description:Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. This is particularly true for patients suffering from Fetal Alcohol Spectrum Disorders (FASD) who exhibit a wide range of cognitive deficiencies including impaired motor skill development. While these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We have previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells lead to altered gene expression in their descendant neurons at the single-cell level. Among the altered genes, we found that an increase of the calcium-activated potassium channel Kcnn2 in subset neurons in the motor cortex correlates with motor skill learning deficits in the mouse model of FASD. We further show that postnatal blocking of Kcnn2 improves these learning deficits. These results propose Kcnn2 blockers as a novel intervention for learning disabilities in FASD and possibly for other neurocognitive conditions.

2021-08-30 | GSE141714 | GEO

DNA methylation signature of human fetal alcohol spectrum disorder

Project description:Prenatal alcohol exposure is the leading preventable cause of behavioural and cognitive deficits, which may affect between 2-5% of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with Fetal Alcohol Spectrum Disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Genome-wide DNA methylation patterns of buccal epithelial cells were analyzed using the Illumina HumanMethylation450 array on a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. After correcting for the effects of genetic background, 658 significantly differentially methylated sites between FASD cases and controls remained, with 41 displaying differences in beta greater than 5%. Furthermore, 203 differentially methylated regions containing 2 or more CpGs were also identified, overlapping with 167 different genes. The majority of differentially methylated genes were highly expressed in samples from the Allen Brain Atlas, which showed high correlations with buccal cell DNA methylation patterns. Furthermore, over-representation analysis of the up-methylated genes displayed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. These findings suggest that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.

2017-04-13 | GSE80261 | GEO

Copy number variation in fetal alcohol spectrum disorder

Project description:The Illumina Human Omni2.5 array is a high resolution microarray platform for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the risk factor CNVs in 95 individuals diagnosed with Fetal alcohol spectrum syndrome (FASD). We also examined 87 age-matched individuals with no symptoms of FASD or any neurodevelopmental disorders. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to FASD.

2018-11-21 | GSE102650 | GEO

Genetics of Epilepsy and Cognitive Disorders: Autism Spectrum Disorders Study

Project description:Genetics of Epilepsy and Cognitive Disorders: Autism Spectrum Disorders Study

| PRJNA213481 | ENA

Kids First: Genetic Spectrum of Vascular Anomalies, Overgrowth and Structural Birth Defects

Project description:Kids First: Genetic Spectrum of Vascular Anomalies, Overgrowth and Structural Birth Defects

| PRJNA760636 | ENA

Kids First Pediatric Research Project on the Genetic Basis of Disorders/Differences of Sex Development (DSD)

Project description:Kids First Pediatric Research Project on the Genetic Basis of Disorders/Differences of Sex Development (DSD)

| PRJNA335781 | ENA

Infant Circulating MicroRNAs as Biomarkers of Effect in Fetal Alcohol Spectrum Disorders

Project description:Infant plasma miRNAs were isolated at 2 weeks and 6.5 months of age from prenatal alcohol exposed and control infants