How to conduct germline sharing WES analysis of three probands in a large family with the same tumour type.

Question

[Maverick77]

I have a question regarding sharing. Is there a 'sharing of the same putitative genes across 3 probands' type of tutorial or pipeline you could point me to?

I essentially have exome data for a trio and 2 other probands in a large family who have all been affected by a certain rare cancer type. These are germline cancers as per pedigree information. I want to see if these probands share any variants or a specific gene region/gene. Ideally to uncover, for example, a truncated protein mutation in all 3 that may cause the disease.

I believe this is more of a downstream analysis question, once a pipeline such as GATK has been completed.

Any help would be greatly appreciated.

[Ram]

How are these "2 other probands" related to the trio?

I don't think their relatedness would be a factor in looking at shared variants unless you wish to track the variant inheritance, for which you will need sequences for almost all family members between the extra probands and the trio.

[Maverick77]

Indeed, it doesn't really matter that they're related. It's basically looking at a trio and seeing what is different in the proband compared to the parents. And then comparing that specific difference to see if it can be found in the other 2 probands

[Ram]

Those are two different steps. For the trio analysis, plinkseq denovo might be of use. For the latter, you might need to use some other plinkseq sub-tool or maybe bcftools.