Getting started with the pedsuite

1. Create a pedigree (pedtools)

We begin by creating and plotting a pedigree with a child of first cousins:

x = cousinPed(1, child = TRUE)
plot(x)

For symmetry let us change the sex of individual 3. We also take the opportunity to showcase some of the plot options (many more are available - see the help page by typing ?plotmethods):

x = swapSex(x, ids = 3)
#> Changing sex of spouses as well: 4

plot(x, 
     hatched = 9, 
     carrier = 7:8,
     fill = list(pink = 1), 
     textAnnot = list(inside = c("1" = "?")))

2. Calculate the inbreeding coefficient (ribd)

The inbreeding coefficient \(f\) of a pedigree member is defined as the probability of autozygosity at a random autosomal locus. That is, the probability that the two homologous alleles have the same origin within the pedigree.

For a child of first cousins one can work out by pen and paper that \(f = 1/16\). Alternatively, we can calculate it with the ribd function inbreeding().

inbreeding(x, ids = 9)
#> [1] 0.0625

The output agrees with \(f = 1/16\).

3. Realised inbreeding (ibdsim2)

For any particular child of first cousins, the actual autozygous fraction of the genome (except X & Y) is called the coefficient of realised inbreeding, denoted \(f_R\). This may deviate substantially from the pedigree-based expectation \(f = 1/16\).

We can simulate the distribution of \(f_R\) with the ibdsim2 package. Since this is not a core package we must load it separately.

library(ibdsim2)

First, we use the function ibdsim() to simulate the recombination process in the entire pedigree, 200 times:

sims = ibdsim(x, N = 200, seed = 123)
#> Simulation parameters:
#> Simulations  : 200
#> Chromosomes  : 1-22
#> Genome length: 2753.93 Mb
#>                2602.29 cM (male)
#>                4180.42 cM (female)
#> Recomb model : chi
#> Target indivs: 1-9
#> Skip recomb  : -
#> Total time used: 1.14 secs

Now extract the autozygous segments of each simulation.

fr = realisedInbreeding(sims, id = 9)

Here is a summary of the first 6 simulations, including the number of segments and various length statistics:

head(fr$perSimulation)
#>   nSeg  meanLen   totLen   maxLen    minLen      fReal
#> 1   11 19.05892 209.6481 37.60149 0.8069583 0.06181840
#> 2   12 14.17339 170.0807 48.43095 1.3405519 0.05015126
#> 3   12 12.87321 154.4785 26.10949 0.1452881 0.04555068
#> 4   19 17.44059 331.3712 58.63821 1.2124618 0.09771059
#> 5   16 16.95554 271.2886 44.95560 1.0034634 0.07999419
#> 6   13 17.84055 231.9271 49.91405 0.9327245 0.06838775

And here is a histogram of the realised inbreeding coefficients (given in the right-most column above):

hist(fr$perSimulation$fReal, xlim = c(0, 0.15), breaks = 16, xlab = "f_R", main = NULL)

# Expected value
abline(v = 1/16, col = 2)

As we see, the distribution centres around the expectation \(f = 1/16 = 0.0625\) (red vertical line) but has substantial spread. The sample standard deviation can be found in fr$stDev, which in our case is 0.02.

4. Marker simulation (forrel)

Note that everything we have done so far has been purely theoretical, with no markers involved. In medical and forensic applications we usually work with genetic data in the form of marker genotypes, so let us simulate such a dataset for our family.

The markerSim() function of the forrel package simulates the genotypes of pedigree members for a specific type of markers. For instance, here we produce 500 SNPs with alleles A and B (equally frequent, by default):

y = markerSim(x, N = 500, alleles = c("A", "B"))
#> Unconditional simulation of 500 autosomal markers.
#> Individuals: 1, 2, 3, 4, 5, 6, 7, 8, 9
#> Allele frequencies:
#>    A   B
#>  0.5 0.5
#> Mutation model: No 
#> 
#> Simulation finished.
#> Calls to `likelihood()`: 0.
#> Total time used: 0.02 seconds.

We can see the genotypes of the first few markers by printing y to the console.

y
#>  id fid mid sex <1> <2> <3> <4> <5>
#>   1   *   *   1 A/B B/B A/A B/B A/A
#>   2   *   *   2 A/B A/B A/B A/A A/B
#>   3   1   2   2 A/B A/B A/B A/B A/B
#>   4   *   *   1 A/B A/B B/B A/B A/B
#>   5   1   2   1 B/B A/B A/B A/B A/A
#>   6   *   *   2 A/B B/B A/A A/B A/A
#>   7   4   3   1 B/B A/A B/B A/B A/B
#>   8   5   6   2 A/B A/B A/B B/B A/A
#>   9   7   8   1 B/B A/A B/B B/B A/A
#> Only 5 (out of 500) markers are shown.

5. Inference of pairwise relationships (forrel)

If this was a real dataset, a natural quality control step would be to check correctness of the pedigree. One way to do this is to use the data to estimate each pairwise relationship, and compare the result with the pedigree. The function checkPairwise() does all of this, and presents the result in a relationship triangle.

checkPairwise(y)
#> Excluding inbred individuals: 9

The plot shows that all pairwise estimates are near their expected location in the triangle.