Ahmedabad: Autism spectrum disorder (ASD) is a puzzle that has baffled doctors worldwide. But a study carried out by an Indian cohort on non-syndromic autism indicate that the solution may be tucked inside just 3% of our DNA. The study, involving families of children with autism, showed that in the majority of cases, mutations could be detected without scanning the entire genome, resulting in sharper, quicker, and far less expensive diagnosis, said researchers.ASD affects more than 1% of the global population and is usually linked to genetic causes. It is characterised by poor social communication and delayed speech development. While ASD often appears alongside syndromes like Rett’s or Fragile-X, cases without these conditions are termed non-syndromic autism, said researchers.In one of the first India-specific studies of its kind, scientists from FRIGE Institute of Human Genetics (IHG) in Ahmedabad and the Centre for Brain Research at the Indian Institute of Science (IISc) in Bengaluru studied 23 families — each consisting of a child with autism and both parents. The study, ‘Long Read Whole Genome Sequencing-Based Discovery of Structural Variants and Their Role in Aetiology of Non-Syndromic Autism Spectrum Disorder in India’ by Jhanvi Shah, Jayesh Sheth, Frenny Sheth, Shweta Ramdas, and Harsh Sheth, among others, was published recently in the BMC journal Medical Genomics.Harsh Sheth, one of the lead researchers, explained the findings in simple terms. “Think of the genome as a book of 3 billion letters. We focused first on the 3% portion that contains 21,000 genes, then examined the rest. Out of all the families studied, only one case showed major mutations in the remaining 97%. For most, analysis of the 3% — known as the exome — was enough,” he said.A striking finding was that in 70% of cases, the mutation was not inherited from parents but occurred spontaneously in the child — a phenomenon known as de novo mutation. This insight, researchers say, could have significant implications for family planning.Cost is another crucial takeaway. Sequencing of the exome (21,000 genes) can be done for as little as Rs 16,000. Whole genome sequencing, however, costs up to Rs 1 lakh per family, making the new discovery vital for affordable diagnostics.Whole genome sequencing used to find structural variantsThe primary highlight of the study, conducted on a subset of 101 parent-child pairs, was the use of long-read whole genome sequencing (lrWGS) with Oxford Nanopore technology, marking a first in the Indian context, according to the researchers, who also established the necessary computing infrastructure.This approach allowed the team to detect structural variants (SVs) that often go unnoticed with conventional techniques such as short-read sequencing or exome sequencing, among others. Sheth said that the findings have potential applications in therapeutics, particularly in planning treatment and enabling early detection of the condition. “Unlike traditional methods, lrWGS can precisely pinpoint the genes associated with the disorder,” he said.
