The Functional Role of Autism Genes Associated With It Was Uncovered In This Study

The Functional Role of Autism Genes Associated With It Was Uncovered In This Study ...

According to the 2018 Centers for Disease Control and Prevention surveillance, one out of 44 children in the United States is diagnosed with autism spectrum disorder (ASD) by the age of 8, but how a child''s DNA has contributed to ASD''s development has been more of a mystery. Recently, clinicians and scientists have looked closely at new, or de novo, DNA modifications, which means they only are present in affected individuals but not in the parents. However, which de novo variants play a role in causing ASD

Researchers at the Baylor College of Medicine and the Texas Childrens Hospital have adopted a new approach to studying ASD genetic variants. In this multi-institutional study, they applied advanced genetic techniques in laboratory fruit flies to determine the functional implications of ASD variants identified in theSimons Simplex Collection (SSC), which includes approximately 2,600 individuals who have autism spectrum disorders. Surprisingly, their research also allowed them to discover a new form of rare disease due to a gene called GLRA2.

ASDs include complex neurodevelopmental difficulties that result in loss of social interaction, communication, and limited interest levels. In the present study, we began our research based on data from a cohort of ASD patients in the SSC, who had genomes and those of their families identified. Our primary objective was to identify gene variants associated with ASD that had a detrimental effect.

The team teamed up with thefruit fly lab to investigate the biological implications of the ASDassociated variants. 79 ASD variants were selected in 74 genes identified in the SSC and studied the effect of each ASDlinked gene variant, compared to the commonly found gene sequence (reference) as a control, from three different perspectives.

Dr. Paul Marcogliese, a co-first author, and a postdoctoral fellow at Dr. Hugo Bellens'' lab, coordinated the work on knocking out the corresponding fly gene, and investigating their biological functions and expression patterns within the nervous system. They then replaced the fly gene with the human gene variant identified in patients, or the reference sequence, and determined how it affected biological functions in the flies.

During our research, Dr. Jonathan Andrews, a postdoctoral fellow at Baylor, investigated how these gene variants affected fly behavior. Several human genes with ASD variants that altered behavior when expressed in flies, demonstrating evidence that these have functional implications.

According to Deal, these two graduate students from Baylors Graduate Programs inDevelopmental BiologyandGenetics and Genomics conducted a research. While some gene variants may lead to complications because they produce defective proteins, others may result in a disease because they cause an overabundance or aberrant function of a particular protein, which can adversely affect biological processes.

ASD-linked human gene variants were investigated by the team for an ensemble of 300 fly strains. The screen showed approximately 40% of the genes for which they were able to perform a comparable functional test.

Some of the variations we examined had functional consequences that were moderately or clearly predicted to be harmful, but others were a surprise. But even the state-of-the-art computational programs couldnt predict they would have detrimental effects, according to Yamamoto. This highlights the value of using multiple, complementary approaches to evaluate genetic variants associated with ASD or other conditions in a living animal. Our fruit fly approach is a valuable tool to investigate the biological relevance of gene variants.

A wealth of data from the researchers revealed gene variants that were previously connected with other neurodevelopmental diseases, and revealed new aspects of genetic diseases'' complexness.

GLRA2 was one gene we focused on to follow up, according to Dr. Ronit Marom, an assistant professor in molecular and human genetics at Baylor University. Among these 13 patients, five males and eight females carried variants of this X-linked gene that had not been previously identified as a neurological disease gene. Apart from that, many of the boys carried developmental delays as the primary reason of their condition, and they also carried gain of function variations.

ASD may not be a single condition involving many genes, according to Wangler, an assistant professor of molecular and human genetics at Baylor, and the co-author of the research. This information is essential for physicians seeing patients with ASD.

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