Journal article

Pooled-parent exome sequencing to prioritise de novo variants in genetic disease

Harriet Dashnow, Katrina Bell, Zornitza Stark, Tiong Tan, Susan White, Alicia Oshlack

Published : 2019


Abstract In the clinical setting, exome sequencing has become standard-of-care in diagnosing rare genetic disorders, however many patients remain unsolved. Trio sequencing has been demonstrated to produce a higher diagnostic yield than singleton (proband-only) sequencing. Parental sequencing is especially useful when a disease is suspected to be caused by a de novo variant in the proband, because parental data provide a strong filter for the majority of variants that are shared by the proband and their parents. However the additional cost of sequencing the parents makes the trio strategy uneconomical for many clinical situations. With two thirds of the sequencing budget being spent on parent..

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