segregatr

The goal of segregatr is to provide segregation analysis for clinical variant classification. For a real-case diagnostic application of the package, see Ratajska et al (2023). The use of segregation analysis in interpretation of sequence variants in SMAD3.

Installation

You can install segregatr from CRAN as follows:

install.packages("segregatr")

Alternatively, obtain the latest development version from GitHub:

devtools::install_github("magnusdv/segregatr")

Example

library(segregatr)

The family below shows four brothers, all affected with a rare dominant disease with 90% penetrance and phenocopy rate 1%. The parents have unknown affection status. All four brothers are shown to carry a candidate variant.

We will use segregatr to analyse the co-segregation of the variant and the disease in this pedigree. Specifically we want to compute the full-likelihood Bayes factor (FLB), quantifying the evidence that the variant is pathogenic.

To create the pedigree we use the nuclearPed() function from the pedtools package, which is automatically loaded together with segregatr.

x = nuclearPed(4)

Then we run the FLB() function, filling in the necessary data:

FLB(x, carriers = 3:6, affected = 3:6, unknown = 1:2,
    freq = 0.0001, penetrances = c(0.01, 0.9, 0.9), proband = 3)
#> [1] 7.732161

The resulting FLB score amounts to suggestive evidence for pathogenicity, according to the thresholds suggested by Jarvik and Browning (2016).