Long Read Sequencing for Rare Disease Research

Rare diseases affect 30 million people in the USA and more than 300-400 million worldwide, often causing chronic illness, disability, and premature death. Most patients with rare or undiagnosed diseases receive only symptomatic treatment. Long-read sequencing technologies may play an important role in discovering novel disease-causing mutations in human diseases with previously unknown underlying genetic causes. CD Genomics is a leading global life sciences company providing professional long read sequencing solutions for rare disease research. We aim to detect disease-causing variants and identify novel disease-associated genes to help you better understand the genetic causes of rare diseases.

Introduction to Rare Diseases

The European Union defines a disease or condition as rare if it affects fewer than 1 in 2,000 people within the general population. Currently, there are over 6,000 known rare diseases and new conditions are being described through medical literature on a regular basis. It is characterized by a wide variety of symptoms and signs that vary not only from disease to disease but also from patient to patient suffering from the same disease. Traditional diagnostic techniques rely heavily on heuristics that combine clinical experience with previous rare disease manifestations with medical literature. Large numbers of patients with rare diseases go undiagnosed for years, and many even die without receiving an accurate diagnosis. In recent years, genome, microarray, and exome sequencing have helped identify the molecular causes of such rare and undiagnosed diseases. However, a large proportion of these patients remain undiagnosed. Despite the drawbacks of high cost and lack of standard analysis methods, several studies have analyzed the genome for pathogenic changes using long-read sequencers.

Fig. 1. Technologies and methods to diagnose rare diseases when exome sequencing is unrevealing. (Marwaha et al., 2022)

Solutions Offering at CD Genomics

Based on advanced PacBio SMRT sequencing and ONT Nanopore sequencing platforms, CD Genomics is committed to providing long read sequencing solutions to support rare disease research. Our whole-genome sequencing approach allows for improved alignment to reference genomes and better detection of structural variation, particularly within regions of repetitive elements, or segmental duplications, or high GC content that are difficult to access using short-read technologies. We enable researchers to delve deeper into the genetic landscape of rare diseases, discover elusive variants, and gain a more complete understanding of underlying genetic mechanisms.

Our comprehensive rare disease research solutions include sample preparation, library construction, sequencing, and advanced bioinformatics analysis to ensure high-quality data and reliable results. Our long read sequencing solutions for rare disease research are as follows.

• Structural Variant Calling in Rare Disease Studies

Rare diseases often involve complex structural variations such as large deletions, duplications, insertions, inversions, and translocations. Accurate detection and characterization of these variants using traditional short-read sequencing methods is challenging. Our long read sequencing solutions overcome this limitation by providing reads spanning the entire length of a genomic region, enabling the detection and precise characterization of complex structural variants with high accuracy. This capability is particularly important in rare disease research, where identification of disease-causing variants is critical.

• Repeated Sequences in Rare Disease Studies

Repeated sequences are abundant in the human genome and are known to play an important role in the pathogenesis of rare diseases. Short-read sequencing technologies have difficulty accurately mapping and assembling repetitive regions, resulting in incomplete or fragmented genomic information. Our long read sequencing solutions resolve repetitive sequences by generating reads spanning these regions, enabling the reconstruction of repetitive elements and facilitating the identification of disease-associated variants in these challenging genomic landscapes.

• Non-coding Regions in Rare Disease Studies

Once considered "junk DNA," non-coding regions of the genome are now recognized as key regulators of gene expression and disease development. Our long read sequencing solutions provide a comprehensive view of the genome by capturing and analyzing these non-coding regions, including enhancers, promoters, and regulatory elements, enhancing your understanding of the genetic basis of rare diseases.

• Transcriptome Analysis in Rare Disease Studies

In rare disease research, understanding gene expression patterns and alterations is critical to elucidating disease mechanisms. Our long read sequencing solutions enable full-length transcriptome analysis, enabling customers to identify rare disease-associated isoforms, alternative splicing events, and novel transcripts.

Advantages of Our Long Read Sequencing Solutions for Rare Disease Research

• Highly accurate long read sequencing produces long reads (25 kb) that span even the largest structural variants and detect larger and more complex variants not detected by short reads.
• Provides a very complete genome assembly with comprehensive variant detection at base pair resolution and phased representation of maternal and paternal haplotypes.
• Enables complete and accurate calling of repeat expansions and identification of medically relevant disrupted sequences and methylation profiles.
• Assist with accurate diagnosis to better manage disease, identify potential treatments, and avoid unnecessary treatments that can have serious side effects.
• A comprehensive picture of pathogenic variants and inheritance patterns helps assess the risk of disease transmission to offspring and aids in the evaluation of alternative family planning options.

CD Genomics is committed to providing accurate, comprehensive, and high-resolution long read sequencing solutions to accelerate rare disease research. If you have any questions, please feel free to contact us. We look forward to working with you on projects of interest.

Related Services

PacBio SMRT Sequencing
Oxford Nanopore Sequencing
Human Whole Genome Sequencing
Human Genome Structural Variation Detection
Full-Length Transcript Sequencing (Iso-Seq)