Caspar SM Dubacher N Kopps AM Meienberg J Henggeler C Matyas G 2018 High-throughput sequencing (HTS) has revolutionized genetics by enabling the detection of sequence variants at hitherto unprecedented large scale. Despite these advances, however, there are still remaining challenges in the complete coverage of targeted regions (genes, exome or genome) as well as in HTS data analysis and interpretation. Moreover, it is easy to get overwhelmed by the plethora of available methods and tools for HTS. Here, we review the step-by-step process from the generation of sequence data to molecular diagnosis of Mendelian diseases. Highlighting advantages and limitations, this review addresses the current state of (1) HTS technologies, considering targeted, whole-exome, and whole-genome sequencing on short- and long-read platforms; (2) read alignment, variant calling and interpretation; as well as (3) regulatory issues related to genetic counseling, reimbursement, and data storage. application/pdf https://sonar.ch/global/documents/235808 eng info:eu-repo/semantics/altIdentifier/doi/10.1111/cge.13190 info:eu-repo/semantics/altIdentifier/pmid/29206278 info:eu-repo/semantics/openAccess Clinical genetics. - 2018 WES WGS genetic counseling genetic testing long-read sequencing next-generation sequencing pharmacogenetics short-read sequencing targeted gene panels Genetic Association Studies Genetic Counseling Genetic Predisposition to Disease Genetic Variation Genome, Human Genome-Wide Association Study Genomics High-Throughput Nucleotide Sequencing Humans Insurance, Health, Reimbursement Sequence Analysis, DNA Clinical sequencing: From raw data to diagnosis with lifetime value. http://purl.org/coar/resource_type/c_6501