Diagnostic yield of 1000 trio analyses with exome and genome sequencing in a clinical setting
A major advantage of trio analysis is the immediate identification of <i>de novo</i> variants as well as confirmation of compound heterozygosity. Additionally, inherited variants from a healthy parent can be dismissed as non-disease causing. The trio strategy enables analysis of a high number of genes-or even the whole genome-simultaneously. The strengths of a trio analysis, in combination with analysis of genome sequence data, allows for the detection of a wide range of genetic aberrations. This enables a high diagnostic yield, even in previously analyzed patients. Our current protocol for trio analysis is based on genome sequencing data, which allows for simultaneous detection of single nucleotide variants, insertion/deletions, structural variants, expanded short tandem repeats, as well as a copy number analysis corresponding to an array-CGH, and analysis regarding <i>SMN1</i> gene copies.
Authors
- Erik Iwarsson (ORCID: https://orcid.org/0000-0002-3827-0263)
- Eva Rudd
- Bianca Tesi (ORCID: https://orcid.org/0000-0002-8253-2507)
- Max Winerdal
- Emma Tham (ORCID: https://orcid.org/0000-0001-6079-164X)
- Magnus Nordenskjöld (ORCID: https://orcid.org/0000-0002-4974-425X)
- Ekaterina Kuchinskaya (ORCID: https://orcid.org/0000-0002-1383-3373)
- Peter Gustafsson
- Giedré Grigelioniené (ORCID: https://orcid.org/0000-0001-9601-3137)
- Daniel Nilsson (ORCID: https://orcid.org/0000-0001-5831-385X)
- Maritta Hellström-Pigg
- Jonas Carlsten
- Johanna Winberg (ORCID: https://orcid.org/0000-0001-6490-4306)
- Karl De Geer (ORCID: https://orcid.org/0000-0001-7849-2082)
- Maria Soller (ORCID: https://orcid.org/0000-0001-9980-8971)
- Anna Hammarsjö (ORCID: https://orcid.org/0000-0001-6585-0944)
- Maria Pettersson (ORCID: https://orcid.org/0000-0003-3120-1625)
- Kristina Lagerstedt‐Robinson (ORCID: https://orcid.org/0000-0001-9848-0468)
- Malin Kvarnung (ORCID: https://orcid.org/0000-0003-0193-0165)
- Eini Westenius (ORCID: https://orcid.org/0000-0001-7674-8101)
- Hillevi Lindelöf
- Ellika Sahlin (ORCID: https://orcid.org/0000-0002-2564-4406)
- Ann Nordgren (ORCID: https://orcid.org/0000-0003-3285-4281)
- Hafdís T. Helgadóttir (ORCID: https://orcid.org/0000-0003-4352-152X)
- Cecilia Arthur (ORCID: https://orcid.org/0000-0002-0645-6530)
- Anna Lindstrand (ORCID: https://orcid.org/0000-0003-0806-5602)
- Helena Malmgren
- Maria Mannila (ORCID: https://orcid.org/0000-0001-6189-2901)
- Valtteri Wirta (ORCID: https://orcid.org/0000-0003-3811-5439)
- Håkan Thonberg
- Britt-Marie Anderlid
- Emma Ehn
Institutions
- Karolinska University Hospital (SE)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
Publication Details
- Journal
- Frontiers in Genetics
- Published
- 2025-06-20
- DOI
- https://doi.org/10.3389/fgene.2025.1580879
- Citations
- 3
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 5.45