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geebee
03-23-2013, 12:49 PM
This is a SNP in the ABO gene.

Most people will have rs41302905 CC. A few, however, will have rs41302905 CT, and an even smaller number may have rs41302905 TT -- although I believe that this will almost always reflect a chip error.

Anyway, if you have either rs41302905 CT or TT, I'd appreciate it if you would post your results for rs41302905 and for two other SNPs: rs8176719 and rs8176747. It would also be helpful if you would post your ABO blood type (if known), and 23andMe's prediction of your blood type and subtypes, or whether the ABO Blood Type lab says "Can't be predicted".

Here's what I'm expecting to find. If you have rs41302905 TT, you will probably get "Can't be predicted". However, your blood type will most likely be B. If you get rs41302905 CT, the lab may or may not be able to make a prediction. If you have rs8176719 DI, there's a good chance it will be able to make a prediction, and the prediction will be O -- with subtypes of some sort of non-deletional O (probably O303), and a deletional O (probably either O112 or O101).

Now, if you really DO have rs41302905 TT, then you would expect to also have rs8176719 II, and you should get a prediction of O, with two non-deletional O alleles. This, I think, is extremely unlikely. But I'd love to hear from you if this is your situation!

I also expect that if you have rs41302905 CT and still don't get a prediction, you most likely have rs8176747 GG. This call will prevent the ABO lab from "seeing" that your subtypes are B101 and O303. B101 would indeed have a "G" here, but O303 would have a "C".

On the chip rs41302905 and rs8176747 are in exactly adjacent positions, and my speculation is that the combination of SNPs for B101 and O303 causes one or both of these positions to be misread as homozygous when it is actually heterozygous.

AJL
03-23-2013, 03:20 PM
Hey geebee, I'm in exactly that situation, as I think we discussed.

rs41302905: CT
rs8176719: II
rs8176747: GG
Result: "Can't be predicted."

However my mother is O101/O303 and my paternal grandfather is B101/O112, and I serotyped B back in biology class. Since my father is also serotyped B while his mother (my grandmother, who was a nurse) was O, that only leaves the possibility that I am B101 + O303, since B101/O112 would not cause this problem.

It would also be interesting to see the results of someone who is, say, A101 + O303, or some othe kind of B + O303.

ilmari
03-24-2013, 06:29 AM
rs41302905 CT
rs8176719 II
rs8176747 GG
Can't be predicted [but I know that I am B+]

geebee
03-24-2013, 07:44 AM
Thanks for the responses, AJL and Ilmari. I actually first learned I was not type B because of a college physiology class. We typed ourselves, and I was sure I'd done something wrong because I came up with O.

Both my parents are B, and I guess they just assumed all of us (six) kids were. Later I ended up giving blood, and the Red Cross said I was O. And since then I've been tested on several occasions, with O as the result each time.

I thought for a while I was the only one of us, but I have a sister who is also type O. Obviously she has to have the same two alleles I do, but I haven't gotten her to test at 23andMe yet. Most likely that won't happen until I offer to pay for it. (I'm from a cheap family.)

With two other untested siblings, both type B, there are three possibilities for each of them. Either could be homozygous B101/B101 like my tested brother; B101/O112 like my tested sister; or B101/O303 like our father. My sister's B101 is clearly the one from our dad, and her O112 is from our mother. The B101/0303 combination could be what either of my untested B siblings has, which would reflect a B101 from our mother and an O303 from our father.

I expect that if that turned out to be the case, that sibling would end up with "Can't be predicted". As far as I know 23andMe doesn't have a single instance of having called someone as B101 O303 -- but that's what I hope to find out. Maybe someone in that category will step forward!

For both of you, I'm curious. Is the call of rs41302905 CT possibly a change? Were you maybe originally called as rs41302905 TT? That's still the call for my father, but if it were changed to CT it would clear up his discordancy with two of his kids.

I think the rs8176747 GG is also iffy though. If it were CG, then your "Can't be predicted" would be resolved instantly. It would become B101 O303 in the ABO Blood Type lab, with no ambiguity.

Lastly ... an interesting thing about B alleles. Other alleles besides B101 exist, but I'm guessing their pretty rare. Among all the B's I've looked at, I haven't seen one so far that was anything else. Also, with a single exception, the only other allele I've seen with O303 has been O112. I did find one person with O303 and O101, though.

It certainly would be interesting to see an A allele with an O303. I wonder what it means that O303 seems mostly to occur along with B101? One would imagine it reflects the populations from which both came -- but what populations were they?

AJL
03-24-2013, 05:18 PM
I don't remember seeing a change but now that I think back, I vaguely remember that when they first released the tool they briefly predicted I was something I clearly am not (either A or O).

My mother is O303 and O101. Although O101 is quite common, of course, the peak of O303 is in Scandinavia, where A is relatively quite common compared to elsewhere, though still in the minority. There's probably a fair pocket of O303/O101 around Scandinavia and a bit in the Baltic.

Thinking to areas where B101/O303 overlap, my ugess is this would occur foremost in north-central Europe/northeastern Europe. B peaks in Eastern Europe to South Asia and East asia, while O303 was not found in a study of Japanese patients but seems to have a scattered presence in Western Europe with the peak in Denmark. You could probably find the B101/O303 combination anywhere in Western Eurasia, but the three of us (your father, geebee; ilmari; and myself) all have some indications of at least some ancestry from around Fennoscandia and something "a little further east." If I were to comapre this blood motif to a yDNA haplogroup, I would guess it might be something like the distribution of yDNA R1a-Z280:

http://www.familytreedna.com/public/r1a/default.aspx?section=results

geebee
03-25-2013, 12:59 AM
^What I'm remembering -- but only vaguely like yourself -- is that you said the lab predicted O2*/O2*. That would suggest the lab was reacting to rs41302905 TT. I also think I'm remembering correctly that at one time your 11 ABO markers were identical to my father's.

Perhaps the v3 chip produced a better read of this marker, though not the adjacent one of rs8176747? My dad's still just on the v2 chip.

The group of people sharing with me at a high enough level to see their ABO lab results in fairly small -- only 64, including myself and the other five profiles I manage. That group only includes two people outside of immediate family members with an O303 allele.

One of these has exactly the same SNPs you do:

rs41302905: CT
rs8176719: II
rs8176747: GG

Of course he also has the "Can't be predicted". From his daughter I know that he doesn't know for sure what his blood type is, but his daughter is AB. It's pretty obvious to me her dad is type B, with subtypes B101 and O303. I know that originally, his rs41302905 was TT, but is now CT like yours and Ilmari's.

I haven't yet found any direct times to Fenno-Scandia, but you're right that a small amount shows pretty consistently across various BGA tests -- including 23andMe's Ancestry Composition, FTDNA's Population Finder, and Ancestry. Not only that, but I would think my father's mtDNA haplogroup of H2a1 might be suggestive of something in that direction. Of course, his mtDNA result is only based on 23andMe's testing, so it's unlikely I'll ever be able to get anything more definitive than that.

AJL
03-25-2013, 01:29 AM
^What I'm remembering -- but only vaguely like yourself -- is that you said the lab predicted O2*/O2*.

Yes, that's rings a bell, now that you mention it! As for V3, no joy there since I upgraded V2>V3 and am still predicted "We think you have blood." :\

geebee
03-25-2013, 02:56 AM
On a side note -- but I believe it has some relevance for this issue -- I ran a comparison of my 23andMe and Ancestry files in one of David Pike's utilities (http://www.math.mun.ca/~dapike/FF23utils/diffs.php). Here's some of what I found:


669639 SNPs appear in both files

0.238 % (1592) of these 669639 common SNPs are NoCalls (i.e. NoCall in at least one file)

0.018 % (121) of the 669639 SNP results differ

83 differing SNPs are both homozygous
6 differing SNPs are homozygous in File1 but not in File2
31 differing SNPs are homozygous in File2 but not in File1

The 83 SNPs that are both homozygous are likely to just be flips, but the important thing in the context of this thread is that there were 37 SNPs homozygous in one file, but heterozygous in the other. I would suspect that, all other things being equal, a heterozygous read is probably a bit more reliable than a homozygous one. The reason is that if you get a homozygous read, it really only tells you that just one allele was detected. It may have been the only allele to detect, but even if a second, different allele happened to be present but undetected, the detected allele would be reported as a pair of matching alleles -- except in cases in which it is known that there is only one SNP at any given position, as in the case of the Y chromosome.

Unfortunately, while rs41302905 is one of the SNPs Ancestry reports, for me it seems to have been a no call (assuming that's what 0 0 means here). I couldn't find rs8176747 or rs8176719 in my Ancestry raw data file. However, I counted a total of 27 ABO SNPs in the Ancestry file -- all of which are included at 23andMe. With the exception of the "no call" at rs41302905, all of the SNPs matched between the two companies.

By way of comparison, I also used one of David Pike's utilities to search for discordancies between my father's 23andMe file and my own. Not including the X and mtDNA -- which of course would not be expected to match between father and son -- I came up with some 23 discordant SNP pairs.

What this means is that the number of differently-called SNPs (not including the flips) is actually greater than the number of parent-child discordancies, although when I compared the two sets of results I didn't find any common SNPs. (SNPs which were different between the two different company's files AND also discordant between my father and me.)

AJL
03-25-2013, 03:52 PM
83 differing SNPs are both homozygous
6 differing SNPs are homozygous in File1 but not in File2
31 differing SNPs are homozygous in File2 but not in File1[/indent]

The 83 SNPs that are both homozygous are likely to just be flips, but the important thing in the context of this thread is that there were 37 SNPs homozygous in one file, but heterozygous in the other. I would suspect that, all other things being equal, a heterozygous read is probably a bit more reliable than a homozygous one. The reason is that if you get a homozygous read, it really only tells you that just one allele was detected. It may have been the only allele to detect, but even if a second, different allele happened to be present but undetected, the detected allele would be reported as a pair of matching alleles -- except in cases in which it is known that there is only one SNP at any given position, as in the case of the Y chromosome.

I suspect you're on to something here. I remember when 23andme reported a transversion on my mtDNA as a more likely transition. (Likelihood isn't everything!)

geebee
03-26-2013, 01:09 AM
^Yes, I've come to the conclusion that people should actually first look at genotyping error as a possibility, before considering mutations, microdeletions, etc. There are certainly times when the latter may account for "unusual" results, but it is obvious that testing errors do occur.

Where two companies report the same SNP differently, I suppose someone who wants the results to always be correct might try to argue it's chimerism, or something like that. But it's clear that the changes are really two minor to be that. Besides, if I'm right that you and Ilmari, as well as the other individual I mentioned, all had rs41302905 TT before you had CT, that in itself shows that errors do occur.

By the way, AJ, is it possible to me to edit the post title, so I can change that silly "interesting" to the "interested" it's supposed to be? I can see how to edit a post, but not the topic title.

geebee
03-26-2013, 02:26 AM
There's an article here (http://bloodjournal.hematologylibrary.org/content/102/8/3035.full.pdf) that people might find of interest.

One item I found especially fascinating was "Figure 3. Overview of ABO gene sequence variations observed in this study." The figure uses various colors to highlight "identical or closely related sequence motifs". A101 was used as the reference allele, and is shown with no added color. I'm guessing that where other alleles also have no added color, they may match the reference allele.

O303 shows sequences that reflect ABO*O01 (O101), ABO*O02 (not sure but I think that may be O112), and ABO*B (B101). Interestingly, there was another allele that seemed to be almost a perfect match for O303 -- differing perhaps by a point mutation or mutations. That was Aw08.

Aw08, as you might expect from the designation, is a very weak A allele. Perhaps that's why Promethease's "best guess" for my blood type is that I "might be an A". Of course, given that 23andMe has absolutely no problem in coming up with O, with subtypes of O112 O303, I'm not sure what the difficulty actually is for Promethease.

AJL
03-26-2013, 04:04 AM
Besides, if I'm right that you and Ilmari, as well as the other individual I mentioned, all had rs41302905 TT before you had CT, that in itself shows that errors do occur.


Yes, I believe that was the case. The error rate does seem pretty low but I think I remember reading that shotgun sequencing is liable to pick up some read errors that traditional (Sanger) sequencing isn't, and vice versa.


By the way, AJ, is it possible to me to edit the post title, so I can change that silly "interesting" to the "interested" it's supposed to be? I can see how to edit a post, but not the topic title.

Fixed!

geebee
03-26-2013, 05:27 AM
^Thanks for fixing the post title for me. It isn't that I don't think I am "interesting" (in a peculiar sort of way), but obviously what I meant here was that "I'm interested ..."

Now none of my former English teachers should have apoplexy, or roll over in their graves -- as the case may be. Now if I could just fix my sentence structure and paragraphing ....

:P

AJL
03-26-2013, 02:18 PM
Now if I could just fix my sentence structure and paragraphing ....

Grammar stilted be not: like Yoda wise, rather. :P

geebee
03-26-2013, 11:26 PM
Too kind you are, AJ. More simply and directly wish I could write. Full paragraphs sentences should be not. :P

geebee
04-15-2013, 08:56 PM
Today I received a sharing invitation from someone who turned out to have no shared segments with any of group. However, the requested (and accepted) level was "with health reports", which made it possible to use the ABO Blood Type predictor.

The interest part is that the sharing includes a brother and a sister who get "Can't be predicted", along with the explanation that "while you have been called on all 11 SNPs used in the ABO analysis, you may have an allele that has not been documented in the scientific literature."

What SNPs do they have? Both have IIGGCCAACTGTCTGGCCCTGG.

This would be

rs8176719 II
rs41302905 CT
rs8176747 GG

It would appear that 23andMe has fixed the problem with rs41302905 showing as TT when it should be CT. Of several people originally called as TT, all but my father are now called as CT.

It would be possible to easily call one allele as B101, but the lab needs to be able to call both alleles in order to work. It can't call the O303 allele, because that would have a C at rs8176747.

geebee
04-16-2013, 02:40 AM
I created an Excel spreadsheet that includes all 70 of the folks sharing with me at the higher level (including health reports). This level permits use of the ABO Blood Type lab.

One of the interesting things I found is that with the exception of folks who have "Can't be predicted", everyone with a "G" at rs8176747 has a B allele. This accounts for 17 people. Two of these have rs8176747 GG, and their predicted subtypes are B101 B101. This combination is actually pretty rare -- rarer than AB, actually.

The only other people in my list who have rs8176747 are six of the seven with "Can't be predicted". The seventh simply has too many called SNPs -- just three. But for the other six, every SNP was called, and they all get that "you may have an allele that has not been documented in the scientific literature" baloney.

Clearly what they actually have is a miscall on rs8176747. Except for folks with two B alleles, this should probably never be GG. Well -- that may be an overstatement. But it certainly looks as if rs8176747 G marks a B allele as surely as rs41302905 T marks a nondeletional O allele.

geebee
04-16-2013, 05:41 AM
I did a sort of the folks in my Excel spreadsheet, one SNP at a time. I excluded the one individual whose "Can't be predicted" was because she was only called on three of the SNPs. Here's what I found:

There are two SNPs that are the same for everyone in the group. Everybody has i4000504 CC, and everyone has i4000504 GG.

rs8176719 Everyone with DD is predicted as type O, with two deletional O alleles of one sort or another; those with DI are predicted to have a single deletional O allele, plus either an A allele, a B allele, or a nondeletional O allele; those with II are predicted as A, B, or AB, or "Can't be predicted"

rs1053878 No one in my group has AA; everyone with AG has a single A allele, though not all those with A alleles have AG; everyone else has GG

rs7853989 Everyone with CC is either in the "Can't be predicted" category, or has two B101 alleles; everyone with a single O303 allele or a single B101 allele has CG; everyone else has GG

rs8176740 No one with AA has an O112 allele; everyone with AT has a single O112 allele; everyone with TT has two O112 alleles.

rs8176743 All those for whom a blood type could be predicted but have no B101 alleles have CC; those with a single B101 allele and five of the six of those who "Can't be predicted" have CT; the remaining person who "Can't be predicted" has TT, as do the two with two B101 alleles

rs41302905 All those who are not in the "Can't be predicted" category and lack an O303 allele have CC; those with a single O303 allele, plus five of the six whose blood type "Can't be predicted", have CT; only the single remaining person whose blood type "Can't be predicted" has TT

rs8176747 Those not in the "Can't be predicted" category have CC, unless they have at least one B101 allele; those with a single B101 allele have CG; everyone in the "Can't be predicted" group has GG, as well as those with two B101 alleles

rs8176749 All those whose blood type is predicted but do not have at least one B101 allele have CC; those with a single B101 allele have CT; those in the "Can't be predicted" category and those with two B101 alleles have TT

As you can see, those in the "Can't be predicted" category were consistently grouped with people with B101. They were also grouped with people with O303. For only one SNP (rs41302905) was anyone in the "Can't be predicted" category alone. That was the single sharer (my father) with rs41302905 TT.

geebee
04-19-2013, 01:40 PM
It would also be interesting to see the results of someone who is, say, A101 + O303, or some othe kind of B + O303.

I've finally found exactly this. I recently got a sharing invitation for a brother and a sister, both of whose 11 ABO SNPs turn out to be exactly the same as yours. They didn't include their mother in the sharing, but her son did recently post her SNPs -- they may have just gotten the data back.

Anyway, it turns out that the ABO Blood Type lab predicts her as A, with probable alleles A101 and O303. The children, however, have to have inherited her O303 allele. The son, at least, says his records show that he has type B blood, which he could only have gotten from his father. (Presumably the same is true for his sister.)

And guess what the ABO Blood Type lab says for both him and his sister: "Can't be predicted."

geebee
04-19-2013, 01:58 PM
There seems to perhaps be a time limit on editing, so I'm using the reply function to issue a correction



There are two SNPs that are the same for everyone in the group. Everybody has i4000504 CC, and everyone has i4000504 GG.

That should read "I4000504 CC" and i4000505 GG"

AJL
04-19-2013, 04:14 PM
I've finally found exactly this. I recently got a sharing invitation for a brother and a sister, both of whose 11 ABO SNPs turn out to be exactly the same as yours. They didn't include their mother in the sharing, but her son did recently post her SNPs -- they may have just gotten the data back.

Anyway, it turns out that the ABO Blood Type lab predicts her as A, with probable alleles A101 and O303. The children, however, have to have inherited her O303 allele. The son, at least, says his records show that he has type B blood, which he could only have gotten from his father. (Presumably the same is true for his sister.)

And guess what the ABO Blood Type lab says for both him and his sister: "Can't be predicted."

Thanks! This sounds like an open-and-shut case.

geebee
04-19-2013, 11:47 PM
Well, I still have three untested sibs myself. I know that one of these is type O, like me. So she should have my O112 combination. The other two have type B, but either may have two B101 alleles like my tested brother, a B101 allele and an O112 allele like my tested sister (and presumably our mother), or a B101 allele and an O303 allele like our father.

One of these days I do plan to order kits for them. Not so much for the blood type info, but to maximize coverage of our mother's genome. I figure that among the six of us, we probably have nearly all of it.

geebee
09-03-2013, 11:41 AM
I've finally gotten round to ordering kits for my three untested siblings. Two of them have type B blood, while the third has type O.

The two with B have three possible combinations:

(1) Two B101 alleles. One of my two siblings who have already tested has this combination.
(2) A B101 allele from our father, and an O112 allele from our mother. The other sibling who has already tested has this combination.
(3) A B101 allele from our mother and an O303 allele from our father. I'm actually hoping at least one of the two untested siblings with type B has this combination. My hypothesis is that a sibling with this combination will be reported as having rs8176747 GG, and will get "Can't be predicted" in the ABO Blood Type lab.

The sibling with type O, one of my three sisters, should have the same two alleles I do: O112 and O303. If so, she should have rs8176747 CC, which of course will be discordant with our father's GG.

AJL
09-07-2013, 05:37 PM
Keep us posted. My grandfather is B101/O112 and that at least shows up properly.

geebee
06-16-2014, 05:42 AM
Just today I noticed something new. Some may remember that originally my father had two ABO SNPs I believed were questionable: rs41302905 TT and rs8176747 GG. The latter was discordant with me, since I have rs8176747 CC. The former wasn't discordant (I have CT), but seemed highly unlikely for someone whose blood type is known to be B.

However, when my father was upgraded from v2 to v3, rs41302905 became CT. This was good, because it turns out that four of his offspring have rs41302905 CC -- so they would have been discordant on this SNP, if not for the change. But rs8176747 remained GG, so it continued to be discordant with me and with my father's sixth offspring, the only other one of us who has type O blood.

This has now changed. 23andMe is reporting my father's rs8176747 as CG. For some reason, the ABO Blood Type lab still isn't calling his blood type, though it is obviously B -- with subtypes of B101 and O303. So this now matches his known blood type, and meshes with his six offspring. In age order, we have these subtypes: B101/O112; B101/B101; O112/O303; B101/O112; B101/O112; O112/O303.

Interestingly, our mother passed on her O112 allele to five out of six of us, and her B101 allele to only one of us.