Geneticist uncovers the history of us

She also uses next-generation genome sequencing to identify the remains of missing Australian soldiers.

As a high schooler, Lyn Griffiths knew she wanted to be a scientist and medical researcher. She resisted being pushed to study medicine or law, preferring to “do something about disorders rather than see people with them’’.

She completed a double degree in biochemistry and microbiology at a time when few women took chemistry, physics or maths, and quips she was one of “four good friends - Dave, Dave, Dave and I’’.

Her pursuit of genes - the molecular blueprint of every living thing – also extends to studying generations of an isolated population on Norfolk Island and using next generational DNA technology to identify the remains of long-fallen soldiers in 20^th century battles.

“I’ve been interested in trying to track down the genes involved in human genetic disorders for more than 30 years,” Professor Griffiths, who heads the QUT Centre for Genomics and Personalised Health, said.

Major headaches

Professor Griffiths is internationally renowned for her research in the genetics of migraine with her research focussed on a cluster of neurovascular disorders including migraine, hereditary stroke, epilepsy, and ataxia movement disorders.

With “overlapping symptoms’’, it can be difficult for clinicians to diagnose which disease a person has. Even though some of these neurovascular conditions are fairly rare - fewer than one in 5000 people are affected - an accurate diagnosis is vital.

“The sort of diagnostics we do are from blood samples ordered by neurologists so they can tell whether a person has a specific mutation in a specific gene.  For these rare monogenic conditions , it means if you have that mutation, you have the disease,’’ Professor Griffiths said.

“It is important to have a definitive diagnosis because each requires a different treatment depending on the mutated gene.

“For instance, familial hemiplegic migraine (FHM) is one of the most severe and uncommon forms. It’s a type of migraine that can cause paralysis of one side of the body that can extend for months. Sometimes people are in a coma with it, and it can occasionally be fatal.

“Hereditary stroke’s most common first symptom is a severe migraine before the stroke but if migraine treatment were to be prescribed it would make it worse, so it is vitally important to distinguish between FHM and hereditary stroke before treatment.

“This is why our focus is on these disorders because our results help the patient and the doctor.”

Isolated populations

For more than 20 years, the small, isolated population of Norfolk Island, between New Zealand and New Caledonia in the Pacific Ocean, has formed a unique, isolated population that has been involved in a genetics health study. 

It has formed an important part of Griffiths’ research in tracking down the genes involved in conditions including migraine, cardiovascular disease, obesity, type-2 diabetes and glaucoma.

“You have lots of good genealogical information and a group of people with a limited number of founders that make it easier to track down genes for disease because they tend to be amplified in that population,” Professor Griffiths said.

“When I first went to Norfolk Island, I didn’t just go there and start a study straightaway. We had a couple of years of discussion with the people as to whether they’d be interested in helping with genetics research, and what would be of help to them in return because why would they do something if there was nothing that helped their island?

“They are fantastic people to work with. My family came over with me the first time I went and set up a clinic in 2000. My kids went to school there. The Norfolk Islanders have their own language, it’s a mix of old English and Tahitian. They are classified as a UN Indigenous people, so their culture is really interesting.

“At the time, they had one doctor on the island for emergency medicine only and there was no public health screening for things like diabetes, so many people weren’t aware of the kinds of disorders they might have.’’

Today, Griffiths and her research team have a more than 20-year collection of genetic information from Norfolk Islanders collected in 2000, in 2009-10 and 2021-22.

“We are using their DNA to track things longitudinally with the same people, and then whole genome sequencing to look for differences in those islanders with a disorder and those without,’’ she said.

“We have found that 25 per cent of Norfolk Islanders have migraines, compared with the general population’s rate of around 12 per cent. It’s not necessarily one or two genes, most migraines have multiple genes and there must be more of them in this population.”

The most recent data collection, that is still being analysed, was funded by industry partner Variant Bio which is interested in tracking down kidney disease genes, as this condition is prevalent in Norfolk Islanders and when found could be extended to the wider population.

“Variant Bio has funded our most recent collection and the whole genome sequencing studies - we haven’t got results yet but we have just finished 1158 people’s whole genomes,’’ she said.

“The company has also provided 10 per cent of the project’s worth to be awarded as community grants for the island and one of these grants is being used to compile a dictionary of their unique language.”

Fallen soldiers

Next-generation sequencing technology used to track down genes in families is also being used for other applications.

Professor Griffiths is working with the Unrecovered War Casualties team in the Australian Army, who seek to find, recover and identify its members missing in action from historic conflicts. There are an estimated 30,000 Australian service members who are unaccounted from WWI and WWII.

Remains are identified through next-generation sequencing and compared with DNA results from relatives of missing soldiers.

"At the moment, we have a pilot research project to develop new methods for highly degraded bone samples from soldiers who died in France and Belgium in WWI and in Papua New Guinea during WWII,’’ Professor Griffiths said.

“Along with this, we have been setting up a biobank of the living relatives of 500 missing soldiers to compare it to. We try to get DNA samples from two female and two male living relatives. We cannot always find very close relatives, sometimes we can’t find any.’’

To date, about 1400 DNA samples have been collected from relatives and are being profiled in terms of mitochondrial and Y chromosomes to be compared with soldiers’ remains.

Most samples, however, are degraded and it can be difficult to extract DNA.

“The bodies in Papua New Guinea have higher levels of degradation than those from Europe, even though the PNG ones are more recent,’’ Professor Griffiths said.

“We've been able to get about nine or 10 out of about 12 or 13 to give us some DNA profiles, but how good they are and whether we can do better is research we're still doing.”

A satisfying career

Professor Griffiths’ research has been supported by more than $57 million in research funding and has been published in more than 440 peer-reviewed international journals.

There have also been many awards along the way including an Order of Australia award (AM) in 2023 for significant services to genetics and to research into neurological disorders.

Professor Griffiths has had no regrets about rejecting other career options and choosing a research path.

“There was absolutely no way I wanted to do that (medicine or law). I’d much rather be in a lab, I’d much rather be a scientist, and I’d much rather do something about disorders rather than see people with them,” she said.

“Even though it was going to be hard, I knew I wanted to do that.”