Genome Sequencing and Rare Genetic Diseases
Author Information
Author(s): Pitsava Georgia, Hawley Megan, Auriga Light, de Dios Ivan, Ko Arthur, Marmolejos Sofia, Almalvez Miguel, Chen Ingrid, Scozzaro Kaylee, Zhao Jianhua, Barrick Rebekah, Mew Nicholas Ah, Fusaro Vincent A., LoTempio Jonathan, Taylor Matthew, Mestroni Luisa, Graw Sharon, Milewicz Dianna, Guo Dongchuan, Murdock David R., Bujakowska Kinga M., UCI-GREGoR Consortium, Xiao Changrui, Délot Emmanuèle C., Berger Seth I., Vilain Eric
Primary Institution: Cold Spring Harbor Laboratory
Hypothesis
Can short-read genome sequencing increase the diagnostic yield in individuals with suspected Mendelian conditions?
Conclusion
Genome sequencing improves the ability to diagnose rare genetic diseases by identifying previously missed variants.
Supporting Evidence
- The study sequenced 353 families, identifying a molecular diagnosis in 54 of them.
- 55.5% of the diagnoses were missed due to original tests not covering the causative variants.
- Deep intronic variants were found to cause abnormal splicing in some cases.
Takeaway
This study shows that using advanced genome sequencing can help find the causes of rare diseases that were missed before.
Methodology
Short-read genome sequencing was performed on individuals with suspected Mendelian conditions who had inconclusive prior genetic tests.
Limitations
The study highlights that some causal variants could still be missed and emphasizes the need for reanalysis of exome datasets.
Participant Demographics
Participants included individuals from 353 families with suspected Mendelian conditions.
Digital Object Identifier (DOI)
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