Genomic Medicine Short Course

Residents, fellows, and junior faculty within 5 years of their terminal degree are eligible for a $500 award which will waive course registration fees. Young investigators who receive the award will be asked to participate in an advisement lunch, whereby they are matched with a senior investigator. The purpose of the lunch is to encourage young investigators and senior investigators to interact, allowing for the discussion of potential shared research interests, as well as giving junior investigators dedicated time with senior personnel. All registrants will be asked if they would like to participate in the lunch. Senior personnel will include external course participants as well as CPGM team members. Interested investigators will be matched according to research interests or subspecialty.

Registrants interested in the Young Investigator Travel award should submit a brief statement summarizing why they would like to attend the course and how it will impact their studies accompanied by a letter of support from their current mentor. Letters should be submitted to genomicmedicinecourse@cmh.edu. A maximum of 10 travel awards will be given and applicants will be notified by email with instructions for registration. These $500 awards can be used to cover registration or used toward travel costs.

The program will begin with an emphasis on understanding genetic mechanisms of disease. Basic principles of genetics and genomics, such as mitochondrial and nuclear DNA variation and applications of genetic testing modalities are addressed. The course will also cover gene regulation, particularly epigenetics in Mendelian and complex disease. Technical aspects of NGS will be discussed, including sample preparation, assay selection, and sequencing platforms. Foundational topics in bioinformatics will include basecalling, alignment, variant detection, and variant annotation.

Current limitations, such as structural variant detection, will be examined. Advances in precision medicine involving pediatric cancer and clinical pharmacology will be covered. Participants will learn about the use of RNAseq and whole genome bisulfite sequencing to detect differences in expression and methylation, and the importance of controlled study design to generate interpretable data. An introduction to data analysis, for expression, transcript detection, and methylation will be covered in advanced workshops.

The curriculum has a multimodal format.

Lectures and case-based learning: The core concepts of the course will be taught by program faculty. A “flipped classroom” approach will be utilized for select topics: online content will be available for viewing prior to class to minimize in-class didactic lecturing in favor of discussion and interaction through hands-on activities and case based learning.

Invited speakers: One dinner program will be hosted focused on ethical and social aspects of genomic medicine. A keynote style lecture features an esteemed investigator to discuss a current topic or advance in genomics.

Workshops: Hands-on use of variant analysis software and databases will occur across computer-based workshops. Participants will be guided through the analysis process, including short read exome and genome analyses, progressing to long-read HiFi genome analysis; encompassing single nucleotide variants, copy number variants, expansions, methylation, and heteroplasmic mitochondrial variants. A dedicated UCSC Browser training workshop will be hosted.

Children’s Mercy Hospital is accredited by the Missouri State Medical Association to provide continuing medical education for physicians.

This course was approved for 25.84 Category 1 Contact hours by NSGC in 2023 and 25.75 AMA PRA Category 1 Credit(s). The 2024 course will be submitted for CEU and CME approval. Attendees should only claim the credit commensurate with the extent of their participation in the activity. 

Registered course participants will be given access to the class portal, which contains course documents and recorded lectures.

Access the class portal

In the CPGM’s Genomic Medicine Course, PGET is used to complement lectures and discussions, directly exposing participants to the magnitude of nonpathogenic human genetic variation and the challenges associated with variant interpretation.

PGET can engage and motivate participants as they learn to use analysis software and variant databases. Genomic sequencing commonly identifies variants of unknown significance (VUS) and rare variants that may be associated with unknowns, such as pleiotropy (the effect of a single gene on multiple phenotypic traits), epistasis (gene–gene interactions), phenotypic heterogeneity, and incomplete penetrance. An additional complication is that variant interpretation may change. A VUS today may become interpreted as benign or pathogenic as genomic reference databases improve. These challenges can be frustrating for clinicians and researchers. In our experience, hands-on exposure to NGS analysis results in a greater tolerance for VUSs and a more sophisticated appreciation of variant ambiguity among our providers.

Approach to Personalized Genomic Education Testing (PGET)

Participants will be offered the unique opportunity of electing to have a NGS panel run on themselves, which can profoundly illustrate teaching points about normal human variation, variants of unknown significance, and unanticipated findings. The panel targets 571 genes that cause childhood onset disease. It was developed by the CPGM for clinical use and has also been utilized for the PGET component of our preexisting genomics course. The panel is optimal for this application because it does not include adult onset disorders, making unexpected diagnoses of a participant unlikely.

Prior to the course, the participants will be assigned a numeric identifier, so their sample can be sent to the CPGM in a de-identified manner for sequencing. Participants will also be provided with an Institutional Review Board (IRB)-approved information sheet that details the following: the methods used for sample and data handling, the likelihood of carrier status detection, and the option of using a preexisting de-identified data file in place of PGET. The de-identified samples are sequenced and analyzed by CPGM personnel who are blinded to the identity of the participant. Course participants will then analyze their own results in a workshop and be allowed to compare their findings to those of an expert reviewer; all findings are then discussed in private with a genetic counselor. In the event participants elect not to have their own panel run, they will also be scheduled to meet with a genetic counselor where the discussion will focus on what the results from the de-identified data would have meant.