Monday, October 3, 2011

Utilizing Your Relatives on 23andMe -- Health Info

Have you ever been curious about which side of the family a particular trait comes from? Ever wondered what traits you and your relatives share in common?

Your 23andMe info can help you find the answers to these sorts of questions.

I will show you how this is done. The first thing you will want to do is download my spreadsheet -- it can be found here. It contains all the info about the location in the genome of the traits and conditions that 23andMe tests for.

The first half of the spreadsheet is in alphabetical order, so that you can quickly find a certain condition that you may be interested in. The second half of the spreadsheet (starting at row 630) is in order by location, so that you can see which traits and conditions fall along a particular segment that you are interested in. After going to the link, you can download the file and save it as you wish so that you can manipulate it to your own preferences.

So how can you use this information?

----------------------------------------------------------------------

Let's say you are curious about which side of the family you might have inherited a certain gene from. As an example, I'll choose APOE, the gene that 23andMe tests for regarding Alzheimer's disease.

My niece Mikayla and her great-grandmother Pearl have both been tested on 23andMe. As you can see, they both have an APOE3 allele -- the question I want to answer is, 'Did Mikayla inherit that APOE3 allele from Pearl?'


(all of the images in this post can be enlarged by clicking on them)

The first thing that I need to do is check the spreadsheet, so that I know where the APOE gene is located.


The gene is on chromosome 19, at approximately location 50,000,000.

The next thing I need to know is whether Mikayla shares a segment at that location with Pearl, her maternal great-grandmother. There are several places I can go to find this information -- Family Inheritance or Family Inheritance: Advanced. I'll choose Family Inheritance because it has a feature that allows you to check for a specific gene -- I can enter APOE in here and see what the exact segment looks like:


This comparison shows that Mikayla and Pearl DO share a segment at the location where the APOE gene is. This means that Mikayla DID inherit her APOE3 allele from her maternal great-grandmother Pearl (we can also conclude that she inherited her other APOE allele, the APOE2 allele, from her father).

I should add that this technique is most useful when you do not have the exact same genotype as your relative. For example, here's what my paternal first cousin and I have for the eye color gene:


We do share a segment at the location where the eye color gene is. But, no real conclusion can be made -- all this tells me is that I inherited either an A or a G at this gene from my dad, which I already knew (everyone gets one allele from their mom and one from their dad).

Your mileage may vary, depending on what question you are asking and what relatives you have available for comparisons, but in general, it's best to use a relative that you only have one allele in common with (for example, in my Alzheimer's example, Mikayla is APOE2/APOE3 and Pearl is APOE3/APOE4. They only have the APOE3 allele in common).

----------------------------------------------------------------------

Let's say you want to take a different approach -- rather than having one specific trait in mind that you want to look at, you want to know which traits or conditions fall along a particular segment that you share with your family member.

First, you need to know which segments of DNA you and your relative share. Here is my comparison with my paternal half-sister. I'll choose chromosome two as an easy example to look at, because my half-sister and I happen to share the full length of our dad's chromosome two with one another.


The next step is to go to the spreadsheet and look and see what traits are shared at this location.


For all of these genes, we inherited the same allele (same version of the gene) from our dad. So what does this tell us? Let's look at one of these traits -- I'll choose lactose intolerance.


Let's take a look at what we see. I am AG at this gene, meaning I have one 'lactose tolerant' allele and one 'lactose intolerant' allele. My half-sister is AA, meaning that she has two 'lactose tolerant' alleles. Because I know we inherited the same allele from our dad, and we have only one allele in common, I know that we inherited our A allele from our dad. Hopefully my reasoning is clear.

I can make several conclusions based on this data. One I already mentioned -- my sister and I inherited an 'A' lactose tolerant allele from our dad. Also, because it takes only one lactose tolerant allele to be lactose tolerant, I know that my dad was lactose tolerant.

----------------------------------------------------------------------

I'll go through one more example, this time with a more distant relative -- my aunt's second cousin.

Here is my aunt's comparison with her second cousin.


I highlighted the segment I want to focus on -- the shared segment at the end of chromosome nine. I want to find out which traits or conditions they share from this segment.

So my next step is to go to the spreadsheet:


Here is a list of traits that they inherited from that chromosome 9 segment. I'll choose blood type as the trait I want to focus on. Let's take a closer look at what their genotypes are for ABO blood type.


So what does this mean? The fact that they have a shared segment at the ABO blood type gene means that at that gene, they inherited a common allele from their common ancestors. They have only one allele in common -- the A allele.

Here's their family tree:


From the DNA evidence, we know that Jason and Dorotha Woodward had at least one A allele between them. One of them (no way to tell whether it was Jason or Dorotha) passed this same A allele to each son, William and Hermon Woodward. William passed the A allele to his son Bruce, who also passed it on to his son. Bruce's son has two A alleles -- he got one from Bruce and one from his mother.

In turn, Hermon passed on his A allele to his daughter Audra Woodward, who then passed it onto Aletha. We can conclude that Aletha got her A allele from her mother and her O allele from her father.

----------------------------------------------------------------------

So, to summarize:

The first step is to decide what question you want to ask.

--------------------

If you have a specific trait in mind (like with the Alzheimer's example) and you want to know which side of the family you inherited a certain allele from, here's what you want to do:

Step One: Go to the spreadsheet and figure out the relevant information. You need to find out where (which chromosome and what position) that trait is located.

Step Two: Go back to 23andMe and see if you've got a relative that will help you. Most likely, you are going to want a relative that (1) has a different genotype than you -- only one allele in common, (2) shares a segment with you at the relevant location and (3) is related to you on only one side of your family.

Step Three: If you have a relative that fits the criteria (also, keep in mind that the criteria will vary based on what type of questions you are asking) -- you can make a conclusion about the trait you selected.

--------------------

On the other hand, if you don't have a specific trait in mind, but you want to look at a specific shared segment and then go from there to figure out which traits were inherited via that segment (like with the second cousin blood type example), here's what you want to do:

Step One: Go to the spreadsheet and figure out the relevant information.  You will probably want to go to the bottom half of the spreadsheet and find the segment, so that you can see what traits fall along that segment.

Step Two: Take a look at the genotypes of you and your relative for those traits. Due to the fact that you have a shared segment with your relative, you know that you and your relative must have at least one allele in common from your shared ancestor for all the relevant traits. The exact conclusions you can make will vary based on your relationship with your relative.

----------------------------------------------------------------------

I think that about covers it!

If you have a question or want me to investigate a specific scenario in your family, please comment on this post or drop me an email at:

Also, if you're going to write about this on your own website, I would love a link back to my website! Thank you!

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