My apologies if this has been asked before or is there is a section regarding such issues already existing, if so, would appreciate if I could be directed there.
Briefly, I am trying to come up with a strategy of selecting samples for an exome sequencing experiment on a complex, infectious disease. I currently have family samples that were previously used in another linkage study for the disease. The sample set consists of some families with 5 affected members, 4 affected members and some with 3 affected members and 2 affected members.
I would like to use samples from the families with 5 and 4 affected members for an exome sequencing run as my first screening step to look for variants. One thing I've read and also have been advised to do is to select the proband and one other distantly related affected family member for sequencing. I've tried to find out why that is the case but I am finding it difficult to understand why that would be a good method? If there are any materials that I can read or look through that might help me understand why this is the case I would greatly appreciate knowing.
Another issue that I have is that my samples do not have variant frequency information in any public database (e.g. 1000 genomes, HapMap). Would it be possible to screen and filter for common variants using another genetically closely related population instead?
Thanks a lot for any advice or help!