Mendelian Inheritance

Promethease 0.1.8 now available with an important new feature called a genoset. Genosets allow us to talk about specific combinations of SNPs.

As an example: 77% of Europeans who lack the rs4988235(T) and rs182549(A) haplotype will be lactose intolerant.

Previous releases could show you had the high risk form of each, but it couldn't highlight that you actually had both. Genosets resolve this. Each genoset gets a unique gs#, similar to an rs#. It also has a criteria which must be met for you to see the consequence. It works like the connection between a genotype and a phenotype.

Here is the genoset which predicts lactose intolerance and it's criteria
http://www.snpedia.com/index.php?title=gs100
http://www.snpedia.com/index.php?title=gs100/criteria

A criteria is a little computer program which evaluates to True or False for your specific genotypes. If True, your report will show the text from the main genoset page. Relax, only hardcore SNPedians will ever see another criteria.

Here's what the promethease reports look like for 23andMe's demo user Lilly Mendel and Greg Mendel.

Lilly Mendel should have no problems with lactose. Greg Mendel is probably lactose intolerant and may also be at increased risk of ALS. But look just below that and you will see that both Mendels carry a rare rs4253208(G;G).

Here from 23andMe's original file is the raw data

rsid	chromosome	position	genotype
rs4253208	10	50348728	GG

And NCBI/HapMap shows that the the (G;G) genotype is possible but rare. In fact it even suggests the Mendels may be closer to African than European ancestry?!

What's actually happening is strand confusion. SNPedia is oriented to NCBI dbSNP. 23andMe probably oriented to the opposite strand. However, there is nothing in their data file which indicates this. Without it, promethease has to recognize the (G;G) as possible.

deCODEme's file format does pass strand information, but perhaps the time has come to consider what a long-term personal genomics file format should look like. XML is well suited to this. Strand information is clearly important. I'd discourage 23andMe's fondness for pushing both allele's together to avoid confusion when dealing with multinucleotide snps such as rs34815109. Ideally it would also be able to handle sequence information since microarrays can't really see haplotypes.

Lastly, several people have reported seeing the message 'Not a win32 application' when trying to run promethease. It seems all were caused by failed downloads. If you see that message please ensure you have the full 7M file from
http://www.snpedia.com/files/promethease/promethease.exe