New findings expand genetic knowledge of autism underpinnings microbiologystudy

Hundreds of novel genetic variants across an ancestrally diverse cohort of 195 families, including 222 people with autism spectrum disorder (ASD), have been identified by researchers at UT Southwestern Medical Center, expanding the catalog of known mutations associated with ASD. The unique variants had not yet been reported in any genomic data from public databases nor were they present in any other individual in the cohort.

In a study published in npj Genomic Medicine, researchers also reported detecting potentially pathogenic variants—which could increase the risk of developing autism—in 73 known ASD or neurodevelopmental disorder genes found in 69 of the individuals with ASD. In addition, the team discovered potentially pathogenic variants in 120 new candidate genes that require further follow-up studies to confirm their role in ASD.

“Research suggests that there may be up to 1,000 genes associated with ASD susceptibility, and the genetic variants identified to date represent just a fraction of the disease burden,” said senior author Maria Chahrour, Ph.D., Associate Professor in the Eugene McDermott Center for Human Growth and Development, the Center for the Genetics of Host Defense, Neuroscience, and Psychiatry.

“We have a long way to go to fully understand the specific genetic causes of ASD, but studies like this one expand our knowledge, enable us to fine-tune future research, and could eventually lead to targeted therapies.”

To identify these mutations and variants, researchers used a technique for studying rare genetic diseases called whole exome sequencing. The process involves analyzing the protein-coding regions of genes in a genome, known as the exome—which represents around 1% of the genome but contains 85% of known disease-related variants.

Whole exome sequencing is faster and less costly than whole genome sequencing. It uses blood, saliva, or cheek swabs to obtain DNA. The sequencing was performed through a collaboration with Regeneron Genetics Center.

The study builds on previous work at UT Southwestern to explore the genetic basis of ASD in diverse populations, including groundbreaking research on a cohort of individuals of East African descent, who have a higher prevalence of the condition than other populations. The enrolled families in the current study, who were primarily from the Dallas-Fort Worth area and included some patients from Children’s Medical Center Dallas, represented African American, Asian, Hispanic, Middle Eastern, Native American, and European ancestral backgrounds.

“Focusing on a diverse, multi-ancestral cohort, as we did in this latest study, helps to identify ancestry-specific effects and improve the interpretation of clinical genetic testing data as we work to unlock the genetic underpinnings of this condition,” said Dr. Chahrour, who is an Investigator in the Peter O’Donnell Jr. Brain Institute.

“In the past, ASD genetics studies have focused almost exclusively on populations of European ancestry, and our goal is to expand the genetic landscape of ASD across multiple ancestries, especially those that are underrepresented.”