eLife Analysis: Scientists have discovered new genes linked to autism in children

Recently, researchers from the University of Texas Southwestern Medical Center and University College London in the United Kingdom published in eLife the results of a study entitled KDM5A mutations in autism spectrum disorder using forward genetics, using a forward genetic method to identify a new GENE associated with ASD KDM5A, whose coding chromatin remodeling agent is essential for gene expression and brain development.
In order to identify the new candidate ASD gene, the researchers used ethyl nitrosium (ENU) to mutulation and breed mice to 3 generations, and then exon sequencing and genotyping of first- and second- and third-generation mice, respectively, combined with the ability of three generations of mice (G3) ultrasonic sound (USV) and the quality of nesting. A total of 350 G3 mice in 8 genealogy were screened, their USV peak frequency decreased and nesting ability was impaired, 409 mutations were carried, esoteric variation related to genotype was detected by linear regression model, and Kdm5a was determined to be a pathogenic allele variant with abnormal USV and nesting behavior, with the function of coding chromosomal remodeling agent.
then tested the gene's physiological function by generating KDM5A to knock out mice.
found that the weight, length, and brain-to-weight ratio were normal compared to the control mice, but the USV emission peak frequency was low and the number of USVs decreased significantly by 84%, in addition, the knock-out mice also showed significant ASD physotypes, including longer self-retouching time, repetitive behavior, and significantly reduced interaction time with the new partner mice by about 50 percent, and morris water maze tests showed that the gene knocked mice showed significant learning and memory disabilities.
Kdm5a mutation leads to abnormal vocal, repetitive behavior and social disorders, learning and memory loss Further evaluation of the role of KDM5A in neuron development, the results show that Kdm5a knocks out the destetic complexity of cortical neurons in mice significantly reduced by nearly 67%, cortical neuron dextive length was significantly reduced by nearly 50%, and the density of dextogenes decreased by about 33%.
Kdm5a gene knocks out degenerates in mice Because this is the first time KDM5A has been found to be associated with ASD, the researchers investigated the presence of KDM5A mutations in people with autism.
In collaboration with an international team of researchers, the researchers identified nine patients with ASD and the pathogenic KDM5A mutation, all of which were clinically epigenetic of ASD and a range of neurodevelopmental disorders, including complete speech deficiency, intellectual disability, and stunting.
further analysis, it was found that the misalmed mutation of KDM5A in these patients led to the loss or decrease of KDM5A transcripts and protein expression.
Maria H Chahrour, co-author of the study on the identification of KDM5A mutations in ASD patients, said: "We have identified a new variant of the autism gene, and we will be looking for more patients with KDM5A mutations, and by better understanding the role of KDM5A in the brain, scientists may be able to find a target to help study possible ways to treat ASD."
we will continue to screen the ASD genes of these animals to theoretically find each gene that works in social behavior and cognition, which is our ultimate goal.
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