Annotating SNPs for promoter and enhancer regions

Question

[siddharth.sethi5]

Hi Everyone,

I am trying to annotate Snps and identify those snps which fall within promoter and enhancer regions. I am doing this using Mouse ENCODE data and have chromatin data for 23 TISSUES.

My question is, In how many tissues a SNP should be found to be annotated as enhancer/promoter to be considered as a regulatory snp?

I find SNPs which fall in enhancer region only in 1 tissue. In other words, that region is annotated as enhancer only in one tissue, other tissues might have no annotation or other annotation. So, would this SNP (enhancer in only 1 tissue) would be interesting/important or it can be incorrect or low confidence annotation and should be ignored?

Also, how similar these chromatin profiles are between tissues?

Would appreciate any kind of help.

Thanks,
Sid

Answer 1

[Emily]

Even if a regulatory feature is only active in one cell type, it's still relevant. Maybe it regulates a gene that's only active in one cell type, or a gene that is active in different pathways in different cell types. If you disrupt TF binding in that enhancer, you can still alter enhancer activity, still alter gene expression and still have a phenotypic effect.

Answer 2

[Shicheng Guo]

Sid, This is the common problem of genetic variation based association study. Usually, we use PBMC as the DNA source to build the association between SNP, CNV with some specific phenotypes for which the disease source might be liver, lung or brain rather than PBMC itself. But we should clear that the genetic variance would bring light influence to our biological system in each tissue with long time (from your born), therefore, if we found some positive and significant association between SNPs and phenotype, we need do our best to interpret the mechanism behind the association.