ADAPTIVE NANOPORE SEQUENCING FOR INHERITED CARDIAC CONDITIONS

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Date

2024-04-19

Authors

Gabdulkayum, Aidana

Journal Title

Journal ISSN

Volume Title

Publisher

Nazarbayev University School of Sciences and Humanities

Abstract

Inherited Cardiac Conditions pose a significant global health burden, described as heart structural or functional anomalies often inherited in an autosomal dominant pattern. It is also highly contributing to the mortality rates. Early diagnosis remains challenging, as most of the individuals may have asymptomatic initial stages subsequently leading to sudden cardiac death, therefore diagnostics is of high significance, especially in younger patients. Current genetic testing methods, such as Sanger sequencing and targeted panels, offer limited insight into structural genetic variations, necessitating the exploration of more comprehensive approaches. This study aims to design and study the adaptive sampling sequencing techniques, a method for targeting specific genomic regions without DNA modifications, for future use in genetic diagnosis for individuals with inherited cardiac conditions and compare the efficiency with currently used next-generation sequencing targeted panels. Through multiple sequencing runs and subsequent analysis, our findings revealed challenges in achieving consistent target region enrichment. The short sequence length observed in our study may contribute to the failure in target enrichment, highlighting the need for longer reads to improve coverage uniformity. Variant analysis using the Epi2me labs platform and annotations revealed the absence of pathogenic variants detected by Oxford Nanopore Technologies (ONT), in comparison with Illumina. This highlights the imperative for enhancing the variant calling algorithm’s sensitivity and specificity. Adaptive sampling sequencing exhibits promise for diagnosis implementation. However, additional optimization is required to improve target region enrichment, particularly through addressing the limitations posed by sequence length.

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Keywords

Type of Access: Embargo, Third-generation sequencing, Oxford Nanopore Technologies, Adaptive Sampling, Inherited Cardiac Conditions, Genetics

Citation

Gabdulkayum. A. (2024). Adaptive Nanopore Sequencing For Inherited Cardiac Conditions. Nazarbayev University School of Sciences and Humanities