Gaby Schobers, Ronny Derks, Amber den Ouden, Hilde Swinkels, Jeroen van Reeuwijk, Ermanno Bosgoed, Dorien Lugtenberg, Su Ming Sun, Jordi Corominas Galbany, Marjan Weiss, Marinus J Blok, Richelle A C M Olde Keizer, Tom Hofste, Debby Hellebrekers, Nicole de Leeuw, Alexander Stegmann, Erik-Jan Kamsteeg, Aimee D C Paulussen, Marjolijn J L Ligtenberg, Xiangqun Zheng Bradley, John Peden, Alejandra Gutierrez, Adam Pullen, Tom Payne, Christian Gilissen, Arthur van den Wijngaard, Han G Brunner, Marcel Nelen, Helger G Yntema, Lisenka E L M Vissers
BACKGROUND: To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efficiency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease. METHODS: We performed short-read GS (NovaSeq™6000; 150 bp paired-end reads, 37 × mean coverage) on 1000 cases with 1271 known clinically relevant variants, identified across different workflows, representative of our tertiary diagnostic centers...
February 14, 2024: Genome Medicine