Improving whole-genome sequencing as a clinical test for intellectual disability

Intellectual disability (ID) is a life-long affliction that impairs the cognitive functioning and adaptive behavior of affected individuals. About two to three percent of people worldwide suffer from ID. ID is mostly caused by irregularities in the DNA of an individual and is the most common reason for genetic testing. There are thousands of different mutations that we now know can cause ID. Diagnosis is necessary for accurate and effective genetic counselling, however deciphering the underlying genetic component remains a challenge.

The emergence of next-generation sequencing technologies, notably whole-genome sequencing (WGS), has empowered the identification of genetic cause in more than half of all patients with severe ID. WGS allows scanning of the entire genome of an individual for abnormalities in DNA sequence. The number of accurate diagnoses are three to four times higher than what is achievable with current methods. The current major limitation is that WGS fails to detect certain types of mutations.

Dr. Rajan Babu’s research aims to improve the clinical effectiveness of WGS by expanding its detection abilities to include all ID-causing pathogenic mutations, including those that aren’t currently being identified. She will employ an advanced WGS technology and analyze the generated data using three well-optimized bioinformatics pipelines, enhancing the diagnostic sensitivity of WGS.

The results of this research will be incorporated in the standard clinical diagnostic evaluation of patients with ID to promote earlier and definitive diagnosis, and enable optimal clinical care and counselling of affected patients and their families. All patients with clinically actionable finding will be offered genetic counselling and consultation with appropriate medical specialists. Ultimately, Dr. Rajan Babu’s research could facilitate discovery of novel genetic aberrations and refine our understanding of the genes and the biological mechanisms involved in ID as well as reveal new potential targets for therapeutic intervention.