[searine]

It can detect whatever variants they put on the SNP chip, be they common or rare. The only caveat is we have to know what variants to put on the chip in the first place. That's the hard part, linking rare variants to disease. After that link is made, the rest is easy.

Is it a sure fire shot to detecting all rare genetic disease? Of course not.

Is it a good way to become aware that I am a carrier for a rare mendelian genetic disease? Yes. Very much yes.

[mnw21cam]

They still have to have good clustering of samples for each variant they are testing. That is, there needs to be a sufficient number of samples in each of the three states (homozygous normal, heterozygous, and homozygous variant) for the software to look at the analogue signals and draw a box around each of the three clusters. This generally prevents the analysis of rare variants using chip technology.

I would be very curious if you could look up the variant that 23andme have reported you have on http://exac.broadinstitute.org/ and let us know the "Allele Frequency" from there.

The thing is, most people are carriers of several rare mendelian diseases. When we do whole exome sequencing, we get on average a couple of hundred rare potentially pathogenic variants in each patient, of which possibly 20 or 30 are actual causes of rare mendelian disease. However, the patients are only carriers of these disease, and are completely irrelevant to their health. The likelihood of them having children with someone who is a carrier for the same condition is very slim (but something we investigate every day).

[searine]

>Allele Frequency

For the particular SNP I am heterozygous for in this particular gene, the population level allele frequency is 0.00001649. Missense mutation. Another variant in this gene, a stop loss, is at 0.0017

Yes, of course the likelihood of it being a problem is slim, but definitely not zero. High enough that it is worth knowing.

>but something we investigate every day

You and me both.