Biobanks from a Pathologist's Viewpoint - CGSI 2023

Explore a comprehensive lecture on biobanks from a pathologist's perspective, delivered by Valerie Arboleda at the Computational Genomics Summer Institute (CGSI) 2023. Delve into the role of pathologists, the ease of sequencing, and the complexities of Mendelian disorders. Examine the factors influencing variable expressivity and phenotype expansion in monogenic disorders. Investigate the challenges of classifying missense variants of uncertain significance (VUS) and learn how ESM1b scores predict the expressivity of monogenic missense variants. Discover the impact of polygenic risk scores (PRS) on carrier phenotypes and understand how common variants affect monogenic variant carriers, using BMI as an example. Gain valuable insights into the intersection of pathology, genomics, and biobanking in this informative 39-minute presentation.

Intro
What is a Pathologist?
Sequencing is Easy
Mendelian (single-gene) disorders a.k.a. monogenic
Other explanations for variable expressivity/expansion of phenotypes?
Having a monogenic disorder, disease-causing mutation does not guarantee the phenotype
Identify the monogenic missense variants that have the highest impact on the phenotype
Classification of missense variants of uncertain significance (VUS) is still an unsolved problem
Expressivity of monogenic missense variants is predicted by ESM1b scores.
Does PRS influence the expressivity of the carrier phenotype?
Common variants directly affect monogenic variant carrier phenotype.
Polygenic risk scores (PRS) quantifies an individual's genetic risk for disease
Common variant effect in noncarriers vs. monogenic variant effect in carriers - BMI