How to choose the best tool for variant trio analysis

Question

[Antonio]

Hi everyone,

I am working on a project about variants in a rare disease in the reproductive field.

I have the BAMs and VCFs of a father, a mother, the girl affected and a brother. I would like to prioritize variants that they could be related to the disease taking into account the information of the family. Therefore, I thought in a trio analysis.

I have been looking up different pipeline on internet, such as GEMINI, Gene.iobio and so on, but I have not achieved to understand properly what tool I should choose for this purpose.

Could you help me?

Thakns.

[luffy]

@antonio, maybe this paper could help you

Answer 1

[Brian Bushnell]

I used to do this kind of analysis a lot but I don't have the pipeline for it anymore. However, I will note that we used to run SNP chips on the extended family (because they are much cheaper than sequencing), and run some software that used it to find crossovers and thus isolate which regions were shared in the affected individuals, then just look at variants in those regions. This is more powerful (if you have a large extended family) than just using a trio because trios still all share hundreds of thousands of variants. But even with cousins, grandparents, etc it was still very hard to find causal variants.

It's also useful to remove high population-allele-frequency variants found in public databases since you're looking for a rare disorder, which presumably would not be caused by a common variant. Between those two approaches you can weed out a lot of candidates...