Human chromosome structural variants (SVs) are balanced/unbalanced genomic abnormalities that include translocation, inversion, insertion and deletion/duplication events with a size of >50bp. The availability of genome sequencing in the research and clinical fields has increased our capacity to detect cryptic SVs and further delineate the complexity of karyotypically/microarray detectable SVs. This increased our knowledge of pathogenicity mechanisms by considering dysregulation of gene expression through position effects and complex interactions between gene dosage and mutational burden. However, much of the contribution of SVs to human disease is left to explore, as the incidence of SVs is still underestimated owing to limitations of current sequencing technologies and analytical pipelines, and few studies have comprehensively integrated SV information with single nucleotide variants in congenital diseases. Rigorous investigation of SV pathogenicity is warranted for clinical applications.
Although recently-published analytical pipelines have shown the feasibility of identification of SVs utilizing short-read and long-read genome sequencing data, the true incidence of simple and complex SVs is yet to be elucidated. Interpretation of pathogenicity by in-silico prediction or experimental assays still falls far behind that of other genomic variants, such as single-nucleotide variants. Furthermore, their contribution to disease, either alone or in combination with other types of genomic variation, remains to be understood.
In this regard, we call for high quality Original Research articles or Reviews that can help update/advance our knowledge of SVs in human disease, emphasizing analytical methods, underlying biology, and clinical applications. Areas of interest include, but are not limited to, the following:
• Methods development for identification of chromosomal structural rearrangements using genomic sequencing approaches, including but not limited to short and long-read sequencing data, etc.
• Epidemiology of SVs in various clinical indications.
• Methodologies for in-silico prediction of the pathogenicity of SVs.
• Studies exploring new pathogenicity contributions of SVs to human diseases.
• The potential clinical application(s) of cryptic SVs detection in prenatal genetic testing and diagnosis.
Human chromosome structural variants (SVs) are balanced/unbalanced genomic abnormalities that include translocation, inversion, insertion and deletion/duplication events with a size of >50bp. The availability of genome sequencing in the research and clinical fields has increased our capacity to detect cryptic SVs and further delineate the complexity of karyotypically/microarray detectable SVs. This increased our knowledge of pathogenicity mechanisms by considering dysregulation of gene expression through position effects and complex interactions between gene dosage and mutational burden. However, much of the contribution of SVs to human disease is left to explore, as the incidence of SVs is still underestimated owing to limitations of current sequencing technologies and analytical pipelines, and few studies have comprehensively integrated SV information with single nucleotide variants in congenital diseases. Rigorous investigation of SV pathogenicity is warranted for clinical applications.
Although recently-published analytical pipelines have shown the feasibility of identification of SVs utilizing short-read and long-read genome sequencing data, the true incidence of simple and complex SVs is yet to be elucidated. Interpretation of pathogenicity by in-silico prediction or experimental assays still falls far behind that of other genomic variants, such as single-nucleotide variants. Furthermore, their contribution to disease, either alone or in combination with other types of genomic variation, remains to be understood.
In this regard, we call for high quality Original Research articles or Reviews that can help update/advance our knowledge of SVs in human disease, emphasizing analytical methods, underlying biology, and clinical applications. Areas of interest include, but are not limited to, the following:
• Methods development for identification of chromosomal structural rearrangements using genomic sequencing approaches, including but not limited to short and long-read sequencing data, etc.
• Epidemiology of SVs in various clinical indications.
• Methodologies for in-silico prediction of the pathogenicity of SVs.
• Studies exploring new pathogenicity contributions of SVs to human diseases.
• The potential clinical application(s) of cryptic SVs detection in prenatal genetic testing and diagnosis.
