Parent-of-origin-aware genomic analysis infers segregation of pathogenic variants

Abstract

Parent-of-origin-aware genomic analysis (POAga) uses Oxford Nanopore Technologies long-read sequencing and single-cell DNA template strand sequencing (Strand-seq) to assign of variants to each biological parent with 99% accuracy using only a blood sample from the child. Pathogenic variants in SDHD and SDHAF2, show parent-of-origin-dependent disease penetrance, with high lifetime risks for paragangliomas and pheochromocytomas when transmitted through the male gamete. Knowledge of parent-of-origin for SDHD and SDHAF2 pathogenic variants is essential when advising on management and has significant clinical implications for lifelong surveillance. However, evaluating segregation currently depends on the availability of parental or family samples for carrier testing or comprehensive clinical information about family cancer history to infers segregation.

Meet the speaker

Dr. Kasmintan Schrader is a Clinician-Scientist, Medical Geneticist who received her PhD in Pathology and Laboratory Medicine at the University of British Columbia.  She trained in cancer susceptibility gene discovery at Memorial Sloan Kettering in New York and returned to BC in 2014 to build the Familial Pancreatic Cancer Program. In 2016, she became co-Medical Director of BC Cancer’s Hereditary Cancer Program and in 2021 was awarded a Tier 2 Canada Research Chair in Clinical Cancer Genetics and Genomics. Dr. Schrader investigates the utility of germline variation in overall cancer care and prevention; to harness precision oncology for the benefit of patients and families.