determine potential SNVs and link them to phenotype

Question

[J.F.Jiang]

Hi all,

Using WGS/WES or target sequencing tech., we find lots of SNVs from a family samples.

However, for a genetic disease, we are not seeking the recurrent SNVs compared to those somatic ones in cancer.

My question is among those thousands SNVs, which SNV could be determined as potential risk markers. Or how can we link these SNV to phenotype?

If anyone here can provide hits, it will be of great help.

Answer 1

[Kizuna]

Your genetic disease is mendelian or complex trait?

If it is inherited as mendelian trait, this post might help.

[J.F.Jiang]

Thanks.

I looked the link you offered.

However, it only takes AD AR, and some hard filteration, such as MAF, inheration into consideration.

Our research is to find the genetic marker in the mendelian disease, that is we are not aiming to find mounts of genes that are associated with the disease, but wish to determine those driver genetic mutations among those detected SNVs.

The useful idea that the topic proposed is that we can prioritize the SNVs. However, I still have no idea how to do such a step. The only thing I can do is to search in pubmed to collect those reported SNV showing critical roles to the disease.

Any one could offer some good ideas?

Answer 2

[Kizuna]

Filtering process is always needed before SNVs or indels prioritization when working with Mendelian diseases.. Thus in Mendelian diseases, SNPs (MAF>1%) are unlikely to play a role.

Candidate mutation prioritization consists into giving the highest priority to stop mutations, splice site mutations, frameshift mutations. So you mainly focus on these variants in the beginig, before investigating missense mutations.

For sure, bibliography search is always needed after filtering and prioritization steps.