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Abstract

Abstract


Objective: The application of next-generation sequencing (NGS) will greatly promote the screening and diagnosis of genetic diseases. This study aimed to implement and validate a targeted NGS panel for genetic screening of over fifty types of genetic disorders in newborns.

Methods: A targeted gene panel consisting of 104 known genes related to genetic diseases with a target size of 347.8 kb was designed. Genes were selected through reference to databases including HGMD, OMIM, GeneReviews®, and Genetic Home Reference, and the latest peer-reviewed publications associated with the genetics of hereditary diseases.

Results: The average coverage for all targeted exons was 596X, and the mean targeted region coverage of 1X, 10X, 20X and 50X reads for each sample were 99.8%, 99.2%, 98.8%, and 95.3%, respectively. The panel showed 100% consistency in detecting 8 pathogenic insertion/deletion (indels) variants ranging from 1 to 16 bp in size and 20 pathogenic single-nucleotide variations (SNVs) across 32 samples previously confirmed by Sanger sequencing.

Conclusions: A dried blood spot (DBS)-based targeted NGS panel for efficient genetic screening of a wide variety of genetic diseases in newborns was developed and evaluated. Furthermore, our panel will contribute to providing accurate diagnosis for genetic disorders and will be helpful for gene therapy for specific diseases.

Keywords: Genetic screening, Next-generation sequencing, Dried blood spot, Inherited metabolic disorders, Gene therapy.