Why is this odd?

[PeterM]

3+ years ago I got OA to analyse my mtDNA. The result was

16148T
16183G
16189C
16223T
16278T

which, after some chasing on my part, they placed in Haplogroup X (Xenia) - on the middle branch - and described as "extremely unusual". Having browsed their forum and this one, I guess it's the 16148T that's odd.

Can anyone out there shed any light on this, please?

Peter

[vraatyah]

if that's the case, the same error occured in Helgason's samples. There is 1 sample 148-183-189-223-278 classified as X, from Scotland. I don't know whether it was checked with RFLPs.

regards
Valery

[vraatyah]

Peter, sorry, you have a transversion at 183, I didn't pay attention to the residue. You should list all your mutations in other manner:
148-183G-189-223-278.

very odd! it's an obvious reason to resequence your sample.

[PeterM]

Thanks, Valery. Although I had the results 3 years ago I've not pursued them till now, so I don't understand some of what you say.

What is the error you refer to (OA seemed reluctant to give me the result, so they may have suspected an error)? Who is Helgason? What is RFLP? What is a transversion (I've noticed that most people with a mutation at 183 follow it with a C)?

I have no ancestral connection with Scotland that I know of. The furthest I've traced my maternal line is to Abingdon, England in the late 18th century.

I sent a sample to Family Tree DNA for sequencing 2 days ago. I'm also getting them to sequence my Y chromosome.

regards, Peter

[vraatyah]

Peter, terrible sorry for confusing you, my first post was absolutely correct )

When I read your post again I thought that 183 site belongs to the stretch whereas C stretch starts at 184. 184G transvertion is extremely unusual but 183G transitions exist in databases and 183C transvertions as well.

CRS
16180
AAAACCCCCTCCCC

your mt
16180
AAAGCCCCCCCCCC

183G has been encountered about 70 times, 2 samples belong to X, both from Scotland. The sequence similar to yours was published by Helgason (unfortunally I forgot where)

[vraatyah]

Since you

have 2 rare (but already encountered!) transitions
don't have any transvertions, particularly rare
have exact match in the same (or close) population


- there is no ABSOLUTE reason to resequence.


Valery

[vraatyah]

there are about 70 hvs1 haplotypes with transition at 183 in our database.

2 sequences fall into X:

1) SCOT193 from Helgason et al

183-223-278

http://www.journals.uchicago.edu/AJHG/journal/issues/v68n3/002146/002146.html

you can find Helgason's sequences in the supplement from McEvoy 2004:

http://www.gen.tcd.ie/molpopgen/data.htm

2) Scottish sample from Helgason (another paper)

148-183-189-223-278

same as yours

[vraatyah]

there is an interesting violation of transition/transversion ratio at 182-183 sites: 30/150 for 182 and 75/300 for 183. This is probably due to adjacent C tract and the real pathway would be as follows:

AAAACCCC -> AA--CCCC -> AACCCCCC

but general rules for alignment force us to list 2 transversions.

[vraatyah]

Peter, I recalled where it was published. see the sequence named EngH65 in McEvoy's supplement

http://www.gen.tcd.ie/molpopgen/data.htm

96 samples from Scotland, all of English descent

[PeterM]

Thanks again, Valery. I cannot open the European mtDNA.zip as my computer tells me the folder is corrupted. Is EngH65 in that one?

I've now read the Richards paper (available through the Macauley link that everyone seems to know) and see that 189-223-278 is identifiably Haplogroup X. But searching the OA database (from which my data seems to have been removed), 148-183 and 183-189 are more frequently found in group H. Any thoughts on what, if anything, I can read into this?

Peter

[CNT]

Thanks again, Valery. I cannot open the European mtDNA.zip as my computer tells me the folder is corrupted. Is EngH65 in that one?
Peter

The mtDNA.zip file is not corrupted,i have just viewed contents - use microsoft excel to view.

Yes,EngH65 is in file ( 1 )

regards,
CNT

[vraatyah]

Hi Peter!

>I cannot open the European mtDNA.zip

when i got the archive after publishing it was safe and sound. It contains about 9000 european sequences of the range 16090-16365 that makes up more than 5000 mitotypes. Although we had > 20000 european sequences, McEvoy's collection added something to our database.

NB! in Mcevoy's archive all the sequences are stored in a different manner: its a list of character strings, all aligned. its not a handy format since you have to compare each sequence with CRS.

>I've now read the Richards paper

thats great reading, its not outdated yet.

there is another paper you should read:

Reidla et al. Origin and Diffusion of mtDNA Haplogroup X
Am. J. Hum. Genet. 73:1178–1190, 2003

available both at AJHG and Tartu web, try evolutsioon.ut.ee

unfortunately, they don't seem to include 183-223-278 sequences in their tree, probably due to lack of HVS2 and coding-region information in Helgason's data.

>189-223-278 is identifiably Haplogroup X

189-223-278 is quite a realiable indicator in Europe, but in whole mtDNA tree it occurs in some African subclades as well as X. As for 189, its a most variable site in human mt. In 1990s haplogroup X was defined via RFLP as +14465 AccI thats equal to 14470C, its the most unambiguous method. If Helgason checked his "X" samples with RFLPs I think you don't need any additional tests. But I have only HVS1 sequences from his study and not aware of defining method. Another possible way is HVS2 sequencing, many Xs have 153 transition, it may help.

How can we classify sequences such as your one without RFLPs and hvs2? There are some HVS1 motifs for X that can facilitate defining. If a eurasian sequence has 189-223-278 it can fall into haplogroups L1 : L2 : L3: D,G : X : other with approximate ratio 15 : 15 : 3 : 6 : 60 : 1. You have neither 227 nor 362 so you are not D,G. To be sure, you may check your mt with 10871MnlI or 14465AccI since Agnar Helgason didn't do the job. I think they are familiar at FTDNA with RFLPs. Another possible way is hvs2 sequencing, 153 or 153-195 would be a sufficient indicator.

regards
Valery