Long Read Sequencing for Neurological Disease Research

Neurological disorders are conditions that affect the brain, spinal cord, and nerves. Neurological diseases have complex phenotypes and their causes may have a polygenic component (e.g., Parkinson's disease, multiple sclerosis, and epilepsy), but the causes are not yet understood. Next-generation sequencing platforms have made huge advances in their ability to identify the genetic causes of many neurological diseases, but are not sufficient to resolve extensions beyond a few kilobases. CD Genomics is a leading global life sciences company providing professional long read sequencing solutions for neurological disease research. Our goal is to detect genomic variants and regions previously thought to be unsequenceable, helping customers more fully understand the genetic basis of neurological diseases.

Introduction to Neurodegenerative Diseases

Neurodegenerative diseases are a class of neurological disorders characterized by a progressive process of cognitive decline, movement disorders, psychiatric disorders, and eventual disability. Neuropathology is characterized by the selective loss or damage of specific neurons in the central and peripheral nervous systems. It is characterized by a progressive process of cognitive decline, movement impairment, psychiatric illness, and eventual disability. Neuropathology is characterized by the selective loss or damage of specific neurons in the central and peripheral nervous systems. The study of pathogenic mutations in human neurodegenerative diseases benefits from large-scale next-generation sequencing (NGS) but is limited by the limitations of short reads (150-300 bp) and underrepresentation of GC-rich/poor regions. Long read sequencing technology offers an alternative strategy compared to NGS, and its unique capabilities make it ideal for interpreting neurodegenerative diseases, especially when NGS receives negative results.

Fig. 1. NGS and Long-read sequencing for diagnosing short tandem repeat expansions. (Chintalaphani et al., 2021)

Solutions Offering at CD Genomics

Our advanced sequencing platforms, such as PacBio SMRT sequencing and ONT Nanopore sequencing platforms, are capable of generating long reads, often spanning thousands of base pairs. CD Genomics is committed to providing long read sequencing solutions to support neurological disease research, allowing researchers to study genomes, transcriptomes, and metagenomes with unprecedented resolution. Our solutions enable the identification of novel mutations in multiple unsolved neurological diseases, the signature of pathogenic repeat expansions, and the direct detection of epigenetic modifications in native DNA. These diseases include Alzheimer's disease, Parkinson's disease, epilepsy and headache disorders, myotonic dystrophy, fragile X syndrome, Huntington's disease, hereditary cerebellar ataxia, amyotrophic lateral sclerosis, frontotemporal disease, etc.

Our long read sequencing solutions for neurological disease research are as follows.

• Detection of Structural Variations

Structural variations, including insertions, deletions, duplications, inversions, and translocations, play an important role in the development and progression of neurological diseases. Due to limited read length, traditional short-read sequencing methods often have difficulty resolving these complex genomic rearrangements accurately. The long reads generated by our long read sequencing platform can provide a comprehensive view of the genome, even in repetitive regions of the genome, and can accurately identify and characterize complex structural variants in neurological diseases. The accurate identification and characterization of these variants is critical to identifying disease-causing genes, unraveling disease mechanisms, and developing targeted therapies.

• Detection of Short Tandem Repeat Amplification

Due to limited read length, short-read sequencing platforms often struggle to accurately resolve the length of these repetitive sequences. Our long read sequencing solutions span the large number of repeat expansions common in neurological diseases and can capture the full length of pathogenic repeat expansions. This capability allows direct measurement of short tandem repeat lengths and comprehensive assessment of their role in the pathogenesis of neurological diseases. Accurately characterizing these repeat expansions helps researchers better understand their impact on gene expression, protein function, and disease progression.

• Phasing and Haplotype Reconstruction

Phasing refers to the determination of parental origins and the arrangement of genetic variation on individual chromosomes. Long read sequencing technology provides the unique ability to phase genetic variation in long DNA fragments. This phasing information is invaluable in neurological disease research as it allows the identification of pathogenic variants and the reconstruction of haplotypes associated with specific phenotypes. CD Genomics' long read sequencing solutions leverage this phasing capability to reveal the complex genetic architecture of neurological diseases, unraveling disease mechanisms and helping to develop personalized treatment strategies.

• Transcriptome Analysis

In addition to genomic analysis, long read sequencing holds great promise for transcriptome analysis in neurological disease research. Traditional short-read RNA sequencing methods often struggle to accurately capture full-length transcripts and accurately quantify isoform expression levels. Our long read sequencing platform enables direct sequencing of full-length transcripts, providing a comprehensive view of the transcriptome and helping to identify alternative splicing events and novel transcripts associated with neurological diseases.

Advantages of Our Long Read Sequencing Solutions for Neurological Disease Research

• Generates long and accurate DNA reads that enable the detection and characterization of genetic variants associated with neurological disorders.
• Performs variant detection and screening of alleles for variants, including SNPs, complex structural variants such as repeat extensions, and long homozygotes.
• RNA sequencing of full-length isoforms of genes associated with neurological disorders to characterize the complete landscape of gene-specific transcripts.
• Detection of novel disease-causing mutations and associated alleles to expand understanding of neurological disorders.

CD Genomics is committed to providing accurate, comprehensive, and high-resolution long read sequencing solutions to accelerate neurological disease research. We aim to help you gain a deeper understanding of the genetic basis of neurological disease and promote more accurate diagnostic and treatment strategies. 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 Genome Structural Variation Detection
Full-Length Transcript Sequencing (Iso-Seq)
Epigenetics and Methylation Analysis Using Long-Read Sequencing