The story behind this post is that my wife recently gave birth to our first son and we experienced a funny story about genetics the day following the birth. Before I start I should say, to reassure the reader, that I have no doubt that I am indeed the father of my child. But as you will see, a non-geneticist might have become worried when faced with the same situation.
Firstly, my wife has a negative rhesus type. This has important medical implications because if the baby were to have a positive rhesus type, she would create antibodies against this marker which could be life-threatening for any subsequent child of positive rhesus type. Basically this is a relatively big deal, but there are ways to deal with this, and therefore knowing the blood type of the baby is essential.
The day after the birth, while we are both lying on our bed, very tired, a midwife comes by and asks us whether we know the rhesus status of the baby. We answer negatively, she checks her notes and says, “Ah, good news, the baby is rhesus negative. The father must also be rhesus negative then!” Well, I am not…
At this very moment, as confident as one can ever be that there is no paternity issue, one cannot help wondering, even for a fraction of a second. The answer is: “Don’t panic”. But still, some harmless checks cannot hurt, right?
What do I know about rhesus type? Not much. The rhesus blood type is defined by a deletion in the RHD gene. Rhesus negative is a recessive trait, which means that my wife’s genotype is -/- (in other words, both of her copies of the RHD gene are deleted). On the other hand, as a known rhesus positive individual I could be +/- (one active and one deleted copy of the gene) or +/+ (both copies of the gene being active). It turns out that I have studied this deletion somewhat in the context of my involvement with the Wellcome Trust Case Control Consortium (WTCCC). In fact we thought for a while that the negative rhesus type was associated with rheumatoid arthritis (until the data proved us wrong and we eventually gave up on that idea).
Now, of interest to this blog, we also looked in this study at single nucleotide polymorphism (SNP) markers that tag this rhesus deletion (the result of this work with the WTCCC can be obtained here). SNPs are exactly the type of markers that 23andMe looks at and therefore some information on rhesus blood type is available in my 23andme data. Our code name for the RHD deletion is CNVR116.1 and the WTCCC file shows that the best tag SNP we have based on our genome map (the HapMap) is rs873308. This SNP rs873308 is indeed a decent marker for the rhesus deletion. In our technical jargon we say that the r-squared is 0.55 (with the RHD deletion causing the negative blood type) and this r-squared value, essentially a correlation coefficient between both markers, is scaled between 0 and 1 (1 being the best possible tag). Note that the lack of an ideal SNP tag (r-quared > 0.9) was an issue for our work in the WTCCC experiment and it cost us some time to assess the rhesus type of our collection of cases and controls.
To obtain the most accurate understanding of the correlation between rs873308 and the RHD deletion I would like to have a large panel of individuals with genotype data for RHD and rs873308. Unfortunately, I don’t have it readily available (even though this probably can be found somewhere). I do have, however, genotype data for another good but slightly less efficient tag rs10903129, which is also on the 23andMe SNP panel. The reason why I have these data is because the same individuals typed for the RHD deletion in the the WTCCC CNV experiment were also typed for SNPs in this related (and initial) study, and this rs10903129 was part of this SNP genotyping array (the Affymetrix 500K). For rs10903129 the r-squared value with the RHD deletion is 0.49. Not ideal, but something relatively good.
Now what do the data tell me? My rs10903129 genotype is AG, which means that I am a heterozygous individual (as opposed to AA or GG, which are homozygous genotypes). Combining existing data for RHD and rs10903129, I find that individuals of European ancestry with the AG genotype (like me) have a 70% chance of being a +/- rhesus individual (as opposed to being +/+ or -/-). In fact, because I know I am not a -/- individual (because my rhesus type is positive) I have a slightly higher probability of being a +/- individual (71% as opposed to a 29% probability of being +/+).
What does this mean for my simple paternity test? As a 71% chance +/- individual, I may very well have passed the negative (-) rhesus type to my son, who also received a negative rhesus type from his -/- mother. Therefore, I have no reason to doubt that I am indeed the father of my son (not that I had any reason to start with!). But if a reader, looking at my data, can convince me that I am indeed a +/+ rhesus type then well… a personal email rather than a public comment would be appreciated of course!
The rather obvious conclusion from this practical genetics experience is that 23andMe genotype data can be used as a paternity test. And of course there are much better ways to do it: the rhesus type represents only a tiny fraction of the available information, but a particularly obvious one. It also seems to me that if genome sequencing at birth becomes a routine test in the future, it probably means that we will have a systematic paternity test for each newborn. I find it to be a rather significant change, and whether it is a good thing is definitely arguable.
And most importantly, midwives making random comments about genetics should know better and not make any comment that is not required. I can imagine that a statement of this type could make a father quite suspicious for no good reason. This being said if both parents have a negative rhesus type (-/-) and the child has a positive rhesus type (so probably +/-) then… well, it’s hard to see how this could happen if the father is indeed the father. But even in this case, I suppose that even a very standard and highly reliable test like rhesus blood type can be mistaken in rare occasions so even this situation is not completely conclusive.
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thanks for those SNPs!
re: paternity issues. i’ve gotten a few rather distressing emails over the years from women who claim to have been subject to accusations of infidelity because of perceptions of deterministic inheritance patterns for visible traits. usually eye color and such. quite often the accusations aren’t from the father, but other relations or acquaintances of the father. i fwd on what i know about the issues, but my sense is that in the cases where i’m contacted the fundamental issues are social psychological, not genetic….
also, a few years back i remember there were debates among genetic counselors as to disclosing to fathers “sensitive” genetic information which might “destabilize” family relations. basically cases where the genetic data implied strongly non-paternity, but either the father didn’t know, or the family didn’t acknowledge the issue, etc. but it seems to me that people were only focusing on one half the ledger. more universal disclosure of this sort of data would probably also dampen unwarranted accusations and/or suspicions. the data we have from paternity cases is that the majority of the time men who are suspicious are actually wrong, and that the child *is* their own. on the other hand, in a substantial minority of instances, far larger than in the population as a whole, the child is not theirs.
The idea of universal paternity testing (or at least universal offering of free voluntary paternity testing) at birth definitely isn’t crazy: as Razib notes, there’s a lot to be said for taking uncertainty out of the equation from the outset.
As large-scale genetic testing becomes more common it will become increasingly difficult to give people medically relevant information while also avoiding any information that might indicate non-paternity. In addition, surreptitious paternity testing will be ever more readily available from off-shore companies. So why not just avoid these complications entirely and have it all sorted out in the maternity ward?
oh my, that was one story… Fun to read about your investigation. I wonder, since you’ve done 23andme, do you have access to all the tests they’ve done or do you get a cd with the data? Do they interpret much or leave it to you? (I’m curious about doing itd, but have some issues with “private information and coorperation”.)
Imho the comments about “inheritance” and “you are this therefore your child is that” is very personal and core private. I don’t really think hospital people should toss them around, especially not when it comes to paternity/maternity issues.
I surely hope we won’t be doing automatically genetic testing at babies at birth. I know that there are some good things looking for certain diseases/mutations but as a general rule my tummy and brain say no.
We did blood typing in my high school and I found out I was AB, came back home and my mother insisted she was 0… so, I assumed I was adopted for a while. No photos of pregger mother and the only blood type not working for an AB ^^ She was mistaken about it however, but it wasn’t the best thing….
That midwife needs to learn some genetics! Rhesus is a classic recessive trait. This sort of nonsense also shows up periodically on TV, when the writers in some soapy program need the tension but are too lazy to look up the genetics (not that I watch much of that sort, but when you are forced to watch for social reasons it comes up)
The other side of the coin is that this sort of check is useful to identify other errors. When my middle brother was born, a nurse announced the blood type as B+ and my mother said that couldn’t possibly be correct, as both she & my father are A+. The nurse apparently went through a “wink-wink, nudge-nudge, say no more routine” with my mother. Of course, it was lab or human error — all three brothers have A+ blood type.
Look up i4001527 on 23andme – this should map fairly accurately to your RH deletion status.
Nick,
I don’t seem to find i4001527 in my 23andMe data file. Do you have any idea why this one is missing?
The probe is available through the 23andMe browser (I’m heterozygous), but it’s marked as “not mapped to a chromosome” – presumably that’s why it hasn’t been included in the raw data.
Nick, any chance you could append these unmapped markers to the end of the raw data files?
Ah, thanks Daniel, so the good news is that I am heterozygous as well :)
And indeed it would be nice to be able to access these data.
Completely off the topic, but the sentence “The day after the birth, while we are both lying on our bed, very tired,” is totally hilarious :D
I enjoyed your story, Vince.
We also encountered confusion about heredity in the hospital. A routine blood screen during my pregnancy identified antibodies, not to D, but to a less common Rhesus antigen. The picture here is a little bit more complicated than for Rhesus D, in that maternal antibodies aren’t necessarily a result of exposure to foetal antigen. We thought the simplest way to find out if our unborn baby might actually have the antigen (and could therefore be at risk from my antibodies) would be to test his father – assuming I am antigen negative, he would have to be positive for it to pass on.
When I requested a blood test for Daniel, my query went from midwives to blood bank nurses. The answer was always no, we couldn’t have a test, and despite my explanations, none of them seemed to understand why we wanted one anyway. As one nurse said, “What you want to do is test the baby. I’m no geneticist, but I’m pretty sure this has nothing to do with the father.”
Vincent,
Of course the information you have doesn’t prove that you are the biological father, just that genetically you could be the father as could any male is who is heterozygous Rh+ or Rh-
So which SNP is the most indicative of Rh status. I am heterozygous for the two SNPs mentioned but the i4001527 SNP is not in my raw data. I think that the SNPs mentioned by the 23 community as indicative of Rh status, I did not have the deletion.
So which is the better SNP to use?
Ponto,
Good question.
Nick, can we take it that i4001527 is a direct probe for the RHD deletion polymorphism?
For what it’s worth, I am a registered blood donor typed A Rhesus negative and my i4001527 genotype is DD which I understand indicates Rhesus negative (DD = negative, II and DI = positive) although 23andMe has not listed this under Traits at this stage.
https://www.23andme.com/you/explorer/snp/?snp_name=i4001527
Let me know if you want any other SNPs from my 23andMe data.
23andMe also accurately predicted my ABO blood group as A here:
https://www.23andme.com/you/labs/abo/
Vincent… I am the father.
Hi there I have a question????? I’m o-blood type and me and my husband ate trying to convince was it hard for you and your wife. We do have one child that I did give birth to years ago at a very young age (yes by my Husband) which was 16 years ago and I’ve had loss of miscarriages already do u think the docs can do anything to help or should I give up trying? Any advice will Belgrade thank u.
Sorry I meant any advice will be great.