Constructing founder sets under allelic and non-allelic homologous recombination

Homologous recombination between the maternal and paternal copies of a chromosome is a key mechanism for human inheritance and shapes population genetic properties of our species. However, a similar mechanism can also act between different copies of the same sequence, then called non-allelic homologous recombination (NAHR). This process can result in genomic rearrangements-including deletion, duplication, and inversion-and is underlying many genomic disorders. Despite its importance for genome evolution and disease, there is a lack of computational models to study genomic loci prone to NAHR. In this work, we propose such a computational model, providing a unified framework for both (allelic) homologous recombination and NAHR. Our model represents a set of genomes as a graph, where haplotypes correspond to walks through this graph. We formulate two founder set problems under our recombination model, provide flow-based algorithms for their solution, describe exact methods to characterize the number of recombinations, and demonstrate scalability to problem instances arising in practice.

Automated summary

Homologous recombination plays a crucial role in human inheritance and population genetic properties. However, non-allelic homologous recombination (NAHR) between different copies of the same sequence can also lead to genomic rearrangements and contribute to genomic disorders. The lack of computational models to study genomic loci prone to NAHR is a gap that needs to be addressed.