23andme.org provides a lot of genetic data, but only reports on a bit. This page is meant to be used as a template for researching further using your own DNA sequence.
- In 23andme view raw data.
- Search for HFE gene.
- Note Chromosome # on top.
- Alternatively download all data and open in a spreadsheet. Use Tab as the delimiter. This will allow you to enter all your notes related to SNPs, but there will be 100s of thousands of rows. Adding a filter to the first line can get you to the right chromosome quickly, but then you will need to scroll to the starting sequence found next. I recommend adding the following column for your notes.
- Example values for these new columns: C/T AA MTHFR int Coronary Artery Disease G/A aa MTHFR F435F Annotated by HGMD but no phenotype description is publicly available
- A=major allele, a=minor allele, int=intron where no protein coding takes place. So AA would be no minor allele, Aa is heterozygous for the minor allele and aa is homozygous for the minor allele. This will allow a filter to quickly bring back all homozygous 'mutations' you have noted. The protein change column will be discussed in subsequent steps.
- Open ensembl.org in a new window.
- Select Human and search for HFE.
- Click on the first result.
- Select 'phenotype' from the left navigation pane.
- Scroll down to the last table.
- Click Show next to all variations with a phenotype annotation.
- Sort by chromosome:base pair (Chr:bp).
- Scroll results to the chromosome noted in 23andme.
- Results will match bp -> position between ensembl and 23andme with phenotypes discussed on the right. The Allele column shows the risk Allele on the right! So if 23andme shows position 26093141 on the HFE gene as AA, that is SNP rs1800562. Ensembl shows this SNP as G/A so an AA means homozygote for the variant (C282Y if you hadn't guessed - we are SNP cousins!). If either of your 23andme results match the variant, then continue research to see if the issue at hand requires having both variants or if just one can also affect you.
- Click the Variant ID or any other link for this SNP in Ensemble to start research or follow the rest of these steps for more info first.
- Next open www.genecards.org in a new window
- Select Symbol Only and search for the same HFE gene.
- Click on the result to get more detail.
- Use the pulldown to jump to section Variants.
- Note these position numbers may not match 23andme position numbers!! This seems to be gene dependent rather than dependent on the (+/-) suffix. For instance the numbers all match for the MTHFR gene, but none match for HFE. I am still researching this.
- Sort 1st on Clinical significance, 2nd on SNP ID.
- Expand the list if there are more Pathogenics and Other than show on the page.
- Match the SNP ID to the ensembl Variant ID.
- This will show all SNPs that research currenlty shows as significant. If the SNP you are researching does not show here then it is not currently known to be a problem. Stop here and repeat for the next SNP of interest if that is the case.
- At this point it may be useful to start your personal notes about which SNP you find showing a variation. Or you could print out the search results from 23andme and keep notes on that print out.
- Click the magnifying glass for more info. This opens a popup window.
- Note the second table. Protein position is where the change shows in the resulting protein. AA Change shows which change occurs in your amino acids. Location Type tells which is a reference value and which is a missense (or other) value. Here is how you see that rs1800562 matches C282Y! Close the popup window to return to genecards.org.
- (If it happens that a pathological or other SNP shows in ensembl but not 23andme, this could be because 23andme did not associate that SNP with the selected gene. Note the rs number (or cut and paste it) and return to 23andme. Clear the gene search and search for this SNP instead. Now 23andme should show that SNP. If is does not then it is because 23andme is not using an rs number for that SNP. If it is important to you, extract all the raw data to an Excel and search for the chromosome and position number in the raw data.)
- In genecards.org, use the pulldown again to jump to section Disorders/Diseases.
- Lots to read here, but for now click the MalaCards link which will open another new window.
- Here you will see a list of ALL maladies associated with this particular SNP. Currently there are 138 of them for C282Y!
- Click on the name of a disease of interest, like hemochromatosis.
- Jump to Section Variations (lots of good info if you want to scroll instead).
- Click the Variation link for the SNP ID or AA Change you want for a summary of disease impact for your specific SNP. This will open a new window with some nice descriptions of the issue at hand and a list of current related publications. Isn't it interesting that they currently list 12 SNPs which can cause hemochromatosis but most doctors only test for 2 or 3!
- Want more? Go back to your open genecards.org window and jump to section Pathways/Interactions. This will list all the related genes to the one you are researching. Now you can go back through this process for each of them! What fun.