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October 7, 2024  |  Rare disease

Child Health Day 2024 – the power of HiFi sequencing in rare disease research

 

Children’s health is central to our future. That’s why we set aside the first Monday of October as Child Health Day to raise awareness about the importance of children’s health and well-being. While many complex facets contribute to children’s well-being, from emotional development to seatbelt use, one crucial factor is unraveling the mystery of unresolved rare diseases. Across the globe, highly accurate long-read sequencing using PacBio technology sheds light on clinically significant genes in previously unresolved pediatric studies. These discoveries empower scientists to support the development of diagnostics for rare and undiagnosed childhood diseases.

 

The challenge of rare disease


By the time families of children with an undiagnosed rare disease reach an expert, they’ve often spent years on an exhausting quest to find the cause of their child’s illness. It can be virtually impossible to diagnose the broad swath of rare diseases in a primary care clinic because there are many unique conditions, and the underlying genetic mechanisms of many rare diseases remain unknown.

Collectively, however, rare diseases are not rare and affect 30 million Americans and 400 million people globally. Rare diseases are often pediatric in nature, with 50% of rare disease diagnoses affecting children. Unfortunately, these diseases can have devastating consequences, and rare diseases are responsible for nearly 20% of infant deaths in the United States. Despite how prevalent and devastating these conditions may be, almost 70% of rare diseases remain undiagnosed due, in part, to the limited capabilities of some genomic technologies.

Undiagnosed rare diseases leave families frustrated without a pathway or plan for treatment. Reaching a diagnosis can give families hope and a path forward.

 

The value of long reads in rare disease research


If techniques like short-read exome and whole genome sequencing fail to provide a diagnosis, where can unseen pathogenic variants be hiding? Many such alterations fall into two primary categories: noncoding regions and structural variants.

Non-coding regions are entirely missed by exome sequencing, which by design focuses exclusively on coding areas. Understandably, non-coding regions have not received the same level of scientific investigation as the coding exome but nonetheless contain critical and highly conserved regulatory areas required to keep the genome functioning properly.

Structural variants that are too complex or large for other technologies to detect represent the second reason some genomic technologies fail to find pathogenic variants in rare diseases. These include but are not limited to, large structural variants like deletions and insertions, repeat expansion, and translocations. HiFi sequencing data consists of extensive long reads that can span large structural variants, giving scientists a more comprehensive view of the genome by revealing the large, complex variants that short reads miss.

 

Unraveling the mysteries of rare disease


The first and most challenging aspect of rare diseases is identifying them, which is essential to providing families with a direction for a treatment plan. The NIH estimates that approximately 80% of rare diseases have a genetic origin, with rare diseases in children having a possibly higher rate. PacBio HiFi sequencing is helping researchers expedite the understanding of possible solutions to these rare diseases.

Researchers at Radboud University Medical Center in the Netherlands aim to reduce the time it takes to identify a rare disease and provide families with answers. Their Department of Human Genetics, one of the largest academic centers for human genetics in Europe, is taking on the challenge of solving some of the most puzzling cases of undiagnosed rare diseases. What tool did they choose to take on this challenge? PacBio HiFi long-read sequencing technology.

 

HiFi sequencing sheds light on rare disease


Radboud University is not alone in choosing highly accurate long-read HiFi sequencing as the solution to advance rare disease research. Other centers, such as Children’s Mercy Kansas City, are also turning to HiFi sequencing.

Children’s Mercy Kansas City is home to the Genomic Answers for Kids rare disease program, which aims to collect genomic data and health information for 30,000 children and their families. The program incorporates highly accurate long-read sequencing to identify underlying genetic causes that were previously undetectable using conventional sequencing methods. Currently, Genomic Answers for Kids has surpassed 1,000 rare disease diagnoses, and ultimately aims to complete nearly 100,000 genomes. The hope is that with these genomes, more revelatory answers for families are sure to come.

 

Increase solve rates in rare disease research with HiFi sequencing


HiFi sequencing is the ideal technology to shed light on previously unresolved medical mysteries in rare diseases. Highly accurate long-read sequencing is helping scientists increase their understanding of undiagnosed diseases and accelerate their understanding of potential solutions. With the power of HiFi sequencing, we can illuminate clinically significant genes in rare diseases and help provide answers for families desperately seeking solutions.

 

Are you interested in learning how HiFi sequencing increases our understanding of undiagnosed rare diseases?


See more in our interview with Care4Rare and explore our customer success story with Children’s Mercy Kansas City. Learn more about HiFi sequencing for rare disease research in this blog post and whitepaper.

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