Genetic Conditions and Rare Disorders

First things first – what exactly are genes?

Every human body is made of billions of cells – the very small units that make up all living things (so small you can only see them with a very strong microscope). Genes contain the information that controls how you grow, develop and function. And they determine most of your physical characteristics, including your gender, blood type, eye colour and height. Many health conditions and diseases are also carried in our genes.

What is a genetic condition?

A genetic condition typically occurs when you inherit an altered gene from your parents that increases your risk of developing that particular condition

Are all genetic conditions inherited?
No, some genetic changes occur randomly before you are born – so not all genetic conditions are passed down from your parents. Environmental or social factors can also cause or contribute to a genetic condition, e.g. being exposed to certain chemicals or radiation. 

The New Zealand situation
The most common life threatening genetic condition affecting New Zealand children is Cystic Fibrosis (CF) – a genetically inherited condition (some people are born with it) mainly affecting the lungs and digestive system.

Why research matters?
27% of unexplained deaths in young people result from a previously undiagnosed genetic condition. And this knowledge is critical to other family members who may have the same condition.

What are we doing to help?

Recently, Dr Nadia Mitchell [bio link] and her team have been studying gene therapy in sheep with the naturally occurring CLN5 form of Batten disease (a terrible neurodegenerative disorder). Their successful studies have led to the first in-human clinical trials (globally) for a gene therapy to fight CLN5 Batten disease.

And Dr Jennifer Hollywood [bio link] and her team have been seeking a better treatment option for kids with cystinosis – a rare genetic disorder only treatable via a medication that is difficult to take and has significant side effects.

And here are some of the current research projects we are funding to help progress scientific discovery – and improve, extend, and save the lives of Kiwi kids living with genetic conditions.

Genomic medicine for whānau: developing a precise genetic test to save lives (and a world-first discovery)

Professor Stephen Robertson, University of Otago

BMedSc, MB, ChB(Otago), FRACP, DPhil(Oxon)

Genomic medicine in New Zealand is advancing rapidly, and this research by Professor Stephen Robertson and his team aims to:

• strengthen Māori-focused genomic resources,
• enhance diagnostic technologies, and
• link genetic insights with nationwide data to better understand health, educational, and social outcomes.

His research team have established a strong national collaboration (coordinated through Starship Hospital) to enrol all children diagnosed with biliary atresia (a liver disease in infants) into this research programme.

Also, they are collaborating closely with scientists at the University of California who have developed the ability to sequence human genomes to the highest quality (and completeness) ever achieved worldwide.

The research team has already sequenced the genomes (i.e. determined the order of the building blocks of a child’s entire DNA or RNA) of 40 children with biliary atresia and their families. The next aim is to sequence the genomes of 10 key affected children using the gold standard level developed with their peers in California.

By identifying the genetic elements that work together to cause this condition, the researchers also hope to develop a test to identify it in newborns.

Ultimately, using genetic screening for these factors will result in earlier diagnosis of this terrible condition and higher survival rates. In his own words, Professor Stephen Roberston says: “Developing a precise genetic test to improve the speed of diagnosis would save children’s lives and be a world-first breakthrough in the care of children with this condition.”

Trialling a treatment for Duchenne muscular dystrophy

Dr Angus Lindsay, University of Canterbury

BSc, MSc, PhD

Muscular dystrophies are a group of genetic disorders that cause the wasting of skeletal muscles – the muscles that connect to bones and allow a wide range of movements and functions. Duchenne muscular dystrophy (DMD) is the most prevalent of these disorders with 20,000 young boys diagnosed globally each year.

DMD primarily affects boys and leads to pre-teen loss of muscle and mobility, and premature death. Low levels of tetrahydrobiopterin (BH4), an antioxidant and important factor involved in blood flow, are found in children with DMD.

Previous research suggests that short-term supplementation of mice (who have DMD) with BH4 may improve the health of skeletal muscle. This research project is exploring the long-term use of a clinically approved form of BH4 to assess its potential to alleviate muscle wasting and premature death in DMD.

The hope is that this treatment, which is already approved for other BH4-deficiency diseases, can be repurposed to reduce muscle wasting and improve the quality of life for boys with DMD.