A Custom Reference Genome can be used with most tools and doesn't really even need to be genomic sequence. It can be any fasta sequence file. If highly fragmented, you may run into memory issues, but you won't know until you try. And if that does occur, moving to a cloud Galaxy can often help (with increased dedicated memory).
Here is how to get started with a Custom Reference Genome (few quick steps): https://wiki.galaxyproject.org/Support#Custom_reference_genome
Look for the "Cloud" link in the side bar of the wiki, should you need to go in that direction.
Best, Jen, Galaxy team