Question: What to do with disease-associated SNPs laying intergenic regions?
gravatar for MadeInEarth
3.4 years ago by
MadeInEarth0 wrote:

From a linkage study, we have identified a significant signal on a chromosomal region. Sequencing that region identified ~1000 significantly associated SNPs laying in intergenic-intron regions with none in exonic regions. Running these SNPs on various databases (e.g. ensembl's VEP) is not getting much results. Any suggestions on how to proceed next? I know a similar question was posted, but that was ~5 years ago so it is probably outdated by now.

snp sequence genome • 1.1k views
ADD COMMENTlink modified 3.4 years ago by WouterDeCoster40k • written 3.4 years ago by MadeInEarth0
gravatar for WouterDeCoster
3.4 years ago by
WouterDeCoster40k wrote:

You could look for eQTL databases, whether SNPs in that region have an effect on a gene further away. Could also be that an unannotated lncgene or miRNA is present there... SNPs can have an effect up to megabases from where they are situated, so it's hard to say what the functional role is. You could look around for ENCODE annotation or riboseq signals to tell you something about functional/transcribed elements. You could give CADD, fathmm or DANN a shot to make a prediction about pathogenicity of variations.

ADD COMMENTlink written 3.4 years ago by WouterDeCoster40k

Thanks. Any suggestions on which eQTL database is the 'best-curated' or 'most-comprehensive'? I put in ' ' since I know this maybe a question with an unlikely answer. More specifically, i suppose there isn't any good databases for trans-eQTL yet which may severely limit my understand of the SNPs function impact in the regulatory network of the trait.

I ran these SNPs on several variant effect predictor databases (e.g. ensembl) that spits out nearly 100+ characteristics/scores that include SIFT, polyphen, PROVEAN, VEST3, MAF, etc, but most the SNPs have blank values for such scores. I am trying to understand why and so far I think the best explanation is that these SNPs have not yet been associated with a disease(?) But this doesn't explain why some scores are empty since they use an algorithm and have the necessary variables (e.g. MSA, surrounding sequencing, biochemical properties, etc) to compute a score. Is there a good explanation to why most of my SNPs do not have an associated score (for like SIFT/PolyPhen/PhastCon)?

ADD REPLYlink written 3.4 years ago by MadeInEarth0

Most of these tools are just for coding variants

ADD REPLYlink written 3.4 years ago by WouterDeCoster40k
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