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Detection of the Copy Number Variants of Genes in Patients with Familial Cardiac Diseases by Massively Parallel Sequencing

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Abstract

Introduction

The implication of copy number variations in familial heart disease is known, although in-depth knowledge is lacking; hence, more studies are needed to further our understanding. Massively parallel sequencing, thanks to its recent surge in use, is emerging as a valid tool for the detection of this type of variant, through the use of appropriate software.

Methods

We conducted a study with 182 patients diagnosed with mendelian cardiovascular diseases who underwent sequencing using a cardiac gene panel and then a specific calling process for copy number variations (CNVs) with ExomeDepth software, which provides us with a Bayes factor (BF), a score of the probability that a CNV detected is true.

Results

After a rigorous CNV prioritization process, we confirmed the variants obtained by MLPA or SNP-based array, finding three real CNVs in five individuals in the MYH11, FBN1 and PDMI7 genes.

Conclusion

The confirmed CNVs present in all cases BF values > 60, thus establishing a threshold to consider real CNVs in the calling process carried out by ExomeDepth on our gene panel.

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Author information

Authors and Affiliations

  1. Cardiovascular Genetics, Santiago de Compostela Health Research Institute, Santiago de Compostela, Spain

    Alejandro Blanco-Verea, Brais Piñeiro, Rocio Gil, Eva Ramos-Luis, María Álvarez-Barredo, Bernardo López-Abel & María Brion

  2. Genomic Medicine Group, Universidade de Santiago de Compostela, Santiago de Compostela, Spain

    Alejandro Blanco-Verea, Rocio Gil, Eva Ramos-Luis, Beatriz Sobrino, Jorge Amigo, Ángel Carracedo & María Brion

  3. Inherited Cardiac Diseases Unit, Department of Cardiology, Santiago de Compostela University Hospital, Santiago de Compostela, Spain

    María Álvarez-Barredo & María Brion

  4. Centre for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, Spain

    María Álvarez-Barredo, José Ramón González-Juanatey & María Brion

  5. Inherited Cardiac Diseases Unit, Department of Paediatric, Santiago de Compostela University Hospital, Santiago de Compostela, Spain

    Bernardo López-Abel

  6. Fundación Pública Galega de Medicina Xenómica, Sistema Galego de Saúde, Santiago de Compostela, Spain

    Beatriz Sobrino, Jorge Amigo & Ángel Carracedo

  7. Centre for Biomedical Network Research on Rare Diseases (CIBERER), Carlos III Health Institute, Madrid, Spain

    Beatriz Sobrino, Jorge Amigo & Ángel Carracedo

  8. Cardiology Department, Santiago de Compostela University Hospital, Santiago de Compostela, Spain

    José Ramón González-Juanatey

Authors
  1. Alejandro Blanco-Verea
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  2. Brais Piñeiro
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  3. Rocio Gil
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  7. Beatriz Sobrino
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  11. María Brion
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Corresponding author

Correspondence to Alejandro Blanco-Verea.

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Funding

This work was partially supported by Plan Estatal de I+D+i 2013-2016, Subdirección General de Evaluación y Fomento de la Investigación (ISCIII-SGEFI) from Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER) (grant numbers PI19/01283, CB16/11/00226, CB06/07/0088).

Conflict of interest

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethics approval

This study was carried out following the guidelines of the Helsinki declaration, its later amendments and the approval of the Santiago-Lugo regional delegation of the Research Ethics Committee of Galicia (protocol code: 2014/295 and 2016/247).

Consent to participate and for publication

All patients who participated in this study signed an informed consent form.

Availability of data

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Author contributions

AB-V had overall responsibility for the methodology, analysis and writing–original draft; BP contributed to methodology, data analysis and revising the manuscript; RG contributed to methodology and revising the manuscript; ER-L contributed to writing and revising the manuscript; MA-B contributed to methodology and revising the manuscript; BL-A contributed to methodology and revising the manuscript; BS contributed to methodology and revising the manuscript; JA contributed to methodology and revising the manuscript; JRG-J contributed to writing and revising the manuscript; ÁC contributed to writing and revising the manuscript; MB has responsibility for the overall execution of the study, contributed to writing and revising the manuscript.

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Blanco-Verea, A., Piñeiro, B., Gil, R. et al. Detection of the Copy Number Variants of Genes in Patients with Familial Cardiac Diseases by Massively Parallel Sequencing. Mol Diagn Ther 27, 105–113 (2023). https://doi.org/10.1007/s40291-022-00624-z

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  • DOI: https://doi.org/10.1007/s40291-022-00624-z

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