On this page, you can have a go at finding a genomic diagnosis through four clinical case studies using a tool called Seave.
Genomics has had a significant impact on medical research for over a decade and has increasing clinical utility for:
- More accurate and earlier diagnosis
- More informed prediction and prevention
- More effective and suitable treatment.
One of the greatest challenges of clinical genomic testing is determining which of the 4 million genetic changes (or variants) in someone's genome could be the cause of their condition. This is often referred to as 'genome filtering'.
Better understanding this process may help you talk to patients and colleagues about genomic testing, and interpret genomic reports.
Before you get started with the case studies, you might want to learn more about the process and the program you'll be using.
Genomic testing has many stages involving a range of experts, as outlined in the below flowchart. Genome filtering can be broken into the stages of variant filtration and variant annotation. In a clinical setting, they would usually be done by pathologists or genomic analysts.
Fig 1. Genomic testing process
Variant filtration involves applying filters to genomic data to go from the millions of variants in a person’s genome, to a number that can be manageably reviewed. This can also be done on the genomes of a few family members together.
Variants are filtered out if:
- the data quality is poor
- they are common in healthy people
- they are unlikely to cause disease (benign/non-pathogenic)
- they don’t match the person’s inheritance pattern
This leaves a subset of around two hundred variants.
Variant annotation is the next step. This is a manual process of reviewing the remaining variants to determine:
- if there is sufficient evidence that they are damaging
- if they are likely to cause or contribute to the person’s phenotype
- if they match the person’s inheritance pattern
Seave is a variant filtration and annotation platform. This online tool takes the millions of variants identified by sequencing an individual or family's genomes and puts them in an easily searchable database.
Seave then lets you filter down to the variants that are likely to cause their condition, and investigate these variants in depth to find a genomic diagnosis.
Seave was designed and built at the Kinghorn Centre for Clinical Genomics (KCCG) by Dr Velimir Gayevskiy.
Seave can be accessed at https://seave.bio.
To get started, you can download the written instructions.
Or watch this instructional video for a more in depth look. It may help to open Seave and follow along in a public database.
The following case studies are aimed primarily at medical specialists, but should be of interest to all health professionals. They can be completed individually, or as part of a team exercise.
Start by downloading the Seave instructions, along with the first case study.
- Case study 1: Aisha (PDF)
- Case study 2: Ali, Sara and Nadia (PDF)
- Case study 3: coming soon
- Case study 4: coming soon
If you have any questions, feedback, or requests please contact us at firstname.lastname@example.org.
This resource was developed with extensive advice and assistance from Dr Velimir Gayevskiy, Dr Georgina Hollway, Dr Kishore Kumar and Dr Lisa Ewans.