Research Highlights

Exome sequencing identifies disease mutations and aids diagnosis

Published online 26 June 2012

Scientists have developed a DNA sequencing technique which can identify new disease-causing mutations and improve diagnosis.

Moheb Costandi

Advances in DNA sequencing technologies enable analysis of the entire genomes of large numbers of people. These methods identified genetic variants associated with disease, but have yet to be successfully translated for clinical use.

Exome sequencing only analyses the 1% of the human genome that encodes for protein, and is therefore faster and more cost effective than whole genome sequencing. The benefits of this selective sequencing have been revealed by an international team, led by Joseph Gleeson of the University of California, San Diego School of Medicine and including researchers from Egypt, Morocco and Qatar. It can be used to identify new disease-causing mutations and also improve diagnosis.

Using exome sequencing Gleeson and his colleagues analysed the DNA of 118 individuals from large inbred families in the Middle East and Asia. The participants suffer from neurodevelopmental disorders such as microcephaly, characterised by an improperly developed brain, and movement disorders caused by malformation of the cerebellum.

In 22 of these patients, the researchers identified mutations in genes that had not been previously linked to disease. One mutation, found in members of a family with microcephaly, was located in the GFM2 gene, which encodes a protein that is involved in energy metabolism. Another was found in a family with Joubert Syndrome, a rare disorder that affects cerebellar development, located in the EXOC8 gene, which encodes a protein essential for synaptic transmission.

In 10 of the patients the results of exome sequencing differed from the clinical diagnoses. This suggests that, at least in some cases, the method can be used to correct or modify initial diagnoses made on the basis of symptoms.

"We have been using exome sequencing with many collaborators in the Middle East for 3 or 4 years," says Gleeson. "It's much more cost-efficient and direct than alternative approaches like single gene sequencing for genetic disorders.

"It's easy to generate exome data for patients, but the interpretation is not so straightforward," he adds. "We had close contact with our collaborating physicians, so we could return to the patients to clarify their history and determine that there were several cases where the genetic testing could correct the diagnosis."


  1. Dixon-Salazar, J., et al. Exome Sequencing Can Improve Diagnosis and Alter Patient Management. Sci. Trans. Med. 4, 138-149 (2012)