Australian Researchers Win Grant to Discover Genetic Mutations

A group of researchers from across Australia will use a $3 million (about $2.2 million US) grant, awarded by the Medical Research Future Fund (MRFF), to find undiscovered genetic mutations underlying Charcot-Marie-Tooth disease (CMT).

Their end goal is to improve the diagnosis of CMT and other rare adult-onset neurogenetic diseases.

Despite the more than 1,000 known mutations in more than 100 CMT-related genes, an estimated 30% to 40% of CMT families remain genetically undiagnosed, researchers note.

“It is exciting to be part of a trans Australian collaboration involving teams in Western Australia, Victoria, South Australia and Queensland,” Marina Kennerson, PhD, scientific director at the Northcott Neuroscience Laboratory of the ANZAC Research Institute and one of the lead researchers under the grant, said in a press release.

Kennerson and Nigel Laing, PhD, of the Harry Perkins Institute of Medical Research in Western Australia, proposed the project with the aim of discovering the genetics underlying the cases of CMT families with no diagnosis. Their teams, and other colleagues from across the country, plan to scan DNA outside of the protein-coding genes that are most frequently associated with health and disease to seek undiscovered genetic mutations.

The set of all protein-coding gene portions is called the exome and the genetic diagnostic technique commonly used to screen for faulty coding genes is known as whole-exome sequencing.

Kennerson and Laing’s project, in contrast, consists of whole-genome sequencing, which takes in a person’s entire genome, including information in non-coding DNA that is key in regulating gene activity.

“Our laboratory has specialized in looking for disease causing DNA re-arrangements known as structural variations and repeat expansions which often lie in the non-coding or ‘junk’ DNA,” Kennerson said. “It is now imperative to investigate the non-coding DNA as it contains important DNA sequences that regulate switching genes on and off.”

Kennerson likens protein-coding genes to light bulbs and the non-coding sequences to the wiring between them.

“If we think of our genes as all the different light bulbs in our household, the focus has been on finding faults in the light bulbs or coding DNA,” she said. “This project will allow us to look for faulty changes not only in novel light bulbs (new genes) but also the in the electrical wiring and power points (non-coding DNA) that are switching the light bulbs on and off.”

The research will be funded by the MRFF, a $20 billion (about $14.7 billion US) long-term investment supporting Australian health and medical research. The MRFF is part of the Australian government’s Department of Health.

Kennerson is an expert in CMT genetics. Her research includes identifying new DNA mutations for preclinical studies, using patient-derived motor neurons and the model organism C. elegans, a worm often used in neurological and developmental biology.

She also is a member of the CMT Research Foundation‘s scientific advisory board and chair of the Scientific Program Committee for the first annual Global CMT Research Convention, coming up in September.

“I am thrilled the government has acknowledged the importance of solving genetically undiagnosed CMT families in Australia and to be recognized as an essential neurogenetics research hub for this trans-Australian collaborative effort,” she said.