find differences between two genomes

[ajthomas]

I have genomic sequencing data from two individuals. These are clones from the same cell line, but they have had a change made by homologous recombination. They should be identical, but one group of clones (all from the same colony) had an unexpected phenotype that can't be explained by the mutation. We sequenced them to try to see if there is some other mutation elsewhere.

What is the best way to compare them to find the differences?

[wkusmire]

You can make a de novo assembling for both of the genomes. Then, you can blast one genome against the other and find differences between them.

[ajthomas]

Maybe I'm missing something here, but it seems to me that a de novo assembly followed by BLAST would be good for finding similar or matching contigs, but not so good at finding differences.

My thought was to map them against a reference genome, then compare the two mapped assemblies. However I'm not sure the best way to go about that. Create a consensus and align the with Mauve or something similar? Create a list of differences from the reference and eliminate all the differences that are the same between the two? Some other approach? In any case, I'm don't know the details of how to go about either of the two approaches mentioned.