Ask HN: How to be my own genetic disease researcher for my partner?
If you truly think this is a rare disease, it&#x27;s very likely that there&#x27;s just one single causal mutation in your partner&#x27;s genome. The easiest way to find that is to:<p>1. Search for variants in that genome where the allele frequency is close to 0 in a very large population e.g. <a href="https:&#x2F;&#x2F;gnomad.broadinstitute.org&#x2F;" rel="nofollow">https:&#x2F;&#x2F;gnomad.broadinstitute.org&#x2F;</a><p>2. Look into variant effects for those you prioritized in step 1 using <a href="https:&#x2F;&#x2F;www.ensembl.org&#x2F;info&#x2F;docs&#x2F;tools&#x2F;vep&#x2F;index.html" rel="nofollow">https:&#x2F;&#x2F;www.ensembl.org&#x2F;info&#x2F;docs&#x2F;tools&#x2F;vep&#x2F;index.html</a><p>Rare diseases are typically due to a coding mutation that alters the protein coding sequence in some significant way.<p>If you need help contact details are on my profile. I do this for a living at a university.<p>rsIDs are a minefield as they change often, there are synonyms and probably you won&#x27;t have all loci properly annotated. Don&#x27;t rely on that too much unless you really know what you are doing.<p>If it&#x27;s not a rare disease, this gets quite more difficult. Also, depending on the whole genome sequencing platform you have used, many structural variants (e.g. deletions or insertions of large chunks of DNA) won&#x27;t be easy to measure.<p>Other comments have suggested Promethease, which will give you a bit of help if it&#x27;s not a rare disease (e.g. if it&#x27;s an autoimmune one, it&#x27;s good at imputing HLA and finding risk haplotypes).<p>My whole comment is a bit of an oversimplification, but I think these suggestions are a good starting point.