Newest Methods for Detecting Structural Variations

• Published in: Trends in biotechnology (Regular ed.) Vol. 37; no. 9; pp. 973 - 982
• Main Authors: De Coster, Wouter, Van Broeckhoven, Christine
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2019; Elsevier Limited
• Subjects: Accuracy; Brain; Brain diseases; Complexity; Dementia; Deoxyribonucleic acid; Disease; DNA; Etiology; Gene sequencing; Genes; Genetic counseling; Genetic screening; genome sequencing; Genomes; inversion; long-read sequencing; Mutation; New technology; structural variants; technology; Therapeutic applications; Belgium; structural variants; genome sequencing; technology; inversion; long-read sequencing
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2019.02.003

A substantial amount of structural variation in the human genome remains uninvestigated due to the limitations of existing technologies, the presence of repetitive sequences, and the complexity of a diploid genome. New technologies have been developed, increasing resolution and appreciation of structural variation and how it affects human diversity and disease. The genetic etiology of most patients with complex disorders such as neurodegenerative brain diseases is not yet elucidated, complicating disease diagnosis, genetic counseling, and understanding of underlying pathological mechanisms needed to develop therapeutic interventions. Here, we focus on innovative progress and opportunities provided by the newest methods such as linked read sequencing, strand-specific sequencing, and long-read sequencing. Finally, we describe a strategy for generating a comprehensive catalog of structural variations across populations. The genetic etiology of complex human diseases is still poorly understood, hampering diagnostics and therapeutic approaches. Short-read sequencing is inadequate for the assessment of structural variation, omitting a substantial amount of human genomic diversity. New developments in genome sequencing technologies enabled the detection of tens of thousands of structural variants per individual. Especially, long-read sequencing is powerful to detect structural variants and repetitive sequences. Strand-seq is the most suitable detection method for chromosomal inversions, a particularly challenging group of structural variants.