Two recent studies using data from the National Genomic Research Library have discovered a small non-coding gene that causes neurodevelopmental disorders. This research highlights the value of exploring the non-coding genome, and the use of large-scale genomic datasets to do this.

What is the non-coding genome?

The non-coding genome refers to the portion of our DNA that does not code for proteins, sometimes known as ‘junk DNA’.

Our genome carries all the genetic information we need for our bodies to produce proteins. These proteins allow us to survive, function, and grow.

Despite this, an estimated 98.5% of our genome does not code for proteins.

We call this portion ‘non-coding’, and its precise function is not entirely understood. However, we do know that parts of it are involved in regulating how our genes are expressed and maintaining the structure of our genome.

What are neurodevelopmental disorders?

Neurodevelopmental disorders are a varied group of conditions that affect the development and function of the brain.

They can impair a person’s ability to learn things, move their body, and communicate, as well as affecting their behaviour. They can range from mild conditions through to requiring lifelong care.

Around 60% of people with neurodevelopmental disorders do not have a genetic diagnosis for the cause of their condition. This is even after extensive genetic testing, which mostly involves looking at protein-coding genes.

Why do we analyse the genome?

Sequencing the genomes of large groups of participants is an important way to help us learn more about non-coding DNA.

By studying genomes on a large scale, researchers can look for patterns in how non-coding genes might affect our health.

To date, the vast majority of known disease-causing genes are in the 1.5% of the genome that codes for proteins.

In contrast, the non-coding genome, (which makes up the remaining 98.5%), has been relatively unexplored, especially regions that are far away from protein-coding genes.

What did these studies find?

2 separate studies from Chen and colleagues, and Greene and colleagues investigated the effect of non-coding DNA on neurodevelopmental disorders.

Both studies used whole genome sequencing data from the National Genomic Research Library, allowing them to compare the genomes of people affected by neurodevelopmental disorders to the genomes of unaffected people.

Using genetic analysis, both groups of researchers found that a small non-coding gene called ‘RNU4-2’ can cause neurodevelopmental symptoms. These symptoms had not previously been tied to any specific gene before.

The study by Greene and colleagues also found that these genetic changes in the RNU4-2 gene are usually ‘spontaneous’. This means they are not typically inherited from parents, but instead happen spontaneously during a person’s early development.

You can learn more about different types of genetic changes in a previous blog.

Why is this significant?

Changes in the RNU4-2 gene are now known to be amongst the most common single-gene causes for neurodevelopmental disorders.

Hundreds of people in the UK, Europe and the US have received diagnoses thanks to these findings, and they could provide a diagnosis for thousands more.

These insights will help to pave the way for effective diagnosis and treatment approaches for neurodevelopmental conditions, highlighting the importance of studying the non-coding genome.

The era of genomic data

As shown by this research, large scale genomic datasets allow researchers to make genetic discoveries at a rate not otherwise possible. The region of DNA identified in this research is not captured by standard tests available in the clinic.

Both studies highlight the power of resources like the National Genomic Research Library to bring answers to patients and their families, when other genetic tests cannot.