A recent study published in The American Journal of Human Genetics by Christian Gilissen, Lisenka Vissers, and their colleagues reveals that a new long-read sequencing technique can detect 80-90% of complex genetic causes more effectively than traditional short-read methods.

In this study, which involved 100 challenging samples, long-read sequencing identified 93% of genetic causes that had previously been difficult to detect with short reads and supplementary tests.

One notable case highlighted in the study showed that long reads successfully identified a rare genetic scenario involving genes from both parents that short reads had missed, showcasing the advanced capabilities of this technology.

As long-read technology becomes more reliable and cost-effective, researchers are increasingly exploring its potential to replace short reads and additional tests in clinical settings.

With ongoing improvements and reduced costs, long-read sequencing is expected to become the preferred method for diagnosing rare disorders due to its quality, simplicity, and affordability.

One of the key advantages of long reads is their ability to directly map DNA methylation, which is crucial for understanding gene activity, a feature that short reads do not provide.

Methods like PacBio HiFi can read segments of up to 20,000 letters, significantly improving the identification of genetic mutations.

Genome sequencing examines the entire human genome, which consists of over 3 billion DNA building blocks, by first breaking it into smaller pieces known as short reads, typically around 300 letters long.

However, short reads often struggle to accurately reassemble DNA, particularly in long repetitive sections and in cases of deletions or rearrangements, which necessitates supplementary testing.

Despite these challenges, genome sequencing is increasingly identifying the causes of rare diseases, which are predominantly genetic in nature.