Hereditary Disease workflows have been developed to support identification of disease-causing mutations in families.
Hereditary diseases can be non-cancer related diseases, such as inherited heart diseases or familial hypercholesterolemia, or it can be inherited cancers such as hereditary colorectal cancer or hereditary breast cancer. In addition to the hereditary diseases, family analysis can help researchers identify rare disease causing mutations that can be:
- a new mutation, also known as a de novo mutation, that is only present in a child and not in any of the parents
- a combination of events that occur in the same gene but at different positions in each of the parents, which is not disease causing by itself in either of the parents, but when both variants are found in a child, it becomes disease causing; this type of variant is known as a compound heterozygous variant.
We offer workflows tailored to two family sizes, 1) a classical "Trio", consisting of a mother, father, and an affected child (the proband), and 2) a "Family of Four", which is mother, father, affected child, and either a sibling in the workflows that detects rare diseases or, in the workflows that detect inherited diseases, an other affected family member, e.g., a sibling or a grand-parent.
These workflows use the "Fixed Ploidy Variant Detection" tool, designed to call variants in samples with known ploidy from read mapping data.
Workflows designed to detect rare variants can both pick up de novo variants as well as compound heterozygous variants.
In addition to the Trio and Family of Four workflows, additional workflows exist that have been designed to pick up variants that are inherited from either the mother or the father.
The available workflows in this category are:
- Filter Causal Variants removes variants outside the target region (only targeted experiments) and common variants present in publicly available databases. Annotates with gene names, conservation scores, and information from relevant databases.
- Identify Causal Inherited Variants in a Family of Four identifies putative disease causing inherited variants by creating a list of variants present in all three affected individuals and subtracting all variants in the unaffected individual. The workflow includes a back-check for all family members.
- Identify Causal Inherited Variants in a Trio identifies putative disease causing inherited variants by creating a list of variants present in both affected individuals and subtracting all variants in the unaffected individual. The workflow includes a back-check for all family members
- Identify Rare Disease Causing Mutations in a Family of Four identifies de novo and compound heterozygous variants from an extended family of four, where the fourth individual is not affected.
- Identify Rare Disease Causing Mutations in a Trio identifies de novo and compound heterozygous variants from a Trio. The workflow includes a back-check for all family members.
- Identify Variants (HD) calls variants in the mapped and locally realigned reads, removes false positives and, in case of a targeted experiment, removes variants outside the targeted region. Variant calling is performed with the Fixed Ploidy Variant Detection tool.