• How large can/should a pedigree be for pedigree-aware read-based phasing (i.e. using option --ped )? The pedigree mode in WhatsHap is intended for intermediate-size pedigrees. The runtime of the core phasing step will be linear in $$2^{2t}$$, where $$t$$ is the number of trio relationships (= number of children) in your pedigree. We do not recommend to use pedigrees with $$t>5$$. For such pedigrees, read-data is unnecessary in most cases anyway and a very high-quality phasing can be obtained by genetic haplotyping methods (like MERLIN).