Figure: A Simulated Pedigree. Referring to the legend, disease-affected individuals (e.g. ID 1) are indicated by red shading on the left side of their symbol.  Individuals who have inherited the causal rare variant (e.g. ID 1) are indicated by blue shading on the right side of their symbol. Individuals who are alive have their age displayed below their symbol (e.g. ID 4).  Individuals who have died have their years of birth and death displayed in parentheses and a diagonal line over their symbol (e.g. ID 5).  The individuals who have developed disease will have a disease-onset age identifier (e.g. ID 1).


Harnessing computational power to illuminate genetic causes in families with disease

The motivation – From targeted gene-therapies to preventive medicine, today's genetic discoveries will shape the future of medicine.  Scientists have had great success using case-control studies to identify common variants associated with common diseases.  However, identifying causal rare variants has proven to be a more challenging task.  While family-based studies are better equipped to identify causal rare variants than case-control studies, data collection for family-based studies is both time-consuming and expensive.

The development – For planning and inference, in collaboration with the British Columbia Cancer Agency's Lymphoid Cancer Families Study, we have developed freely available software, SimRVPedigree, to simulate pedigrees sampled to contain disease-affected relatives.  Pedigrees are detailed family records that describe both the individual members as well their relationships.  SimRVPedigree simulates pedigrees dynamically, allowing for birth, disease-onset, and death at the individual level.  At the family level, users can model complex sampling criteria for the study.

Its significance –To our knowledge, SimRVPedigree is the first software to simulate the underlying genetic cause in disease-affected families and allow for realistic sampling of families enriched for disease.  SimRVPedigree may be used for a variety of tasks such as refining the criteria for sampling families to maximize the proportion of genetic cases and to study potential bias that may affect findings.  Furthermore, it can be used to identify characteristics of pedigrees to follow up for genetic causes.

Read the paper – “Simulating pedigrees ascertained for multiple disease-affected relatives” by Nieuwoudt, C; Jones, SJ; Brooks-Wilson, A; Graham, J. (2018). Source Code for Biology and Medicine 13:2. DOI: 10.1186/s13029-018-0069-6.

Website article compiled by Jacqueline Watson with Theresa Kitos