Dr. Bryan Sykes on Genetic Testing
Douglas Richardson
Those of you interested in the current status of DNA research may find
the following recent letter written by Bryan Sykes, Ph.D.,
informative. The original letter was written to a woman named "Anne,"
who posted a copy of it on another forum. In his letter, Dr. Sykes
explains the process of distinguishing different genetic markers in
order to classify DNA into various clans. As we learn more about
these markers, we're better able to sort people into groupings.
Needless to say, some of the language is technical.
Best always, Douglas Richardson, Salt Lake City, Utah
E-mail: royala...@msn.com
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GENEALOGY-DNA-L Archives
From: "Annie, The WritingTeacher" <writing...@hotmail.com>
Subject: [DNA] Letter to me from Bryan Sykes on distinguishing H from
U4 with 356
Date: Thu, 05 Sep 2002 09:29:59 -0700
Dear Anne,
David Ashworth from Oxford Ancestors has shown me you message and the
replies you received from Drs Macaulay and Villems about whether your
DNA
sequence places you in the clade of U4 Ulrike or H Helena.
David tells me that on your original certificate, issued in August
2000, you
were placed in the clan of Helena but that when you were sent a
replacement
you had become a daughter of Ulrike instead. Of course your actual DNA
sequence hadn't changed, but the assignment of you clan had. It may
help if
I explain how that is done. Clans are defined by a mixture of two
sorts of
genetic markers, the variants in the control region sequence and the
variants at a number of other sites around the mtDNA molecule - now
generally called SNPs (short for Single Nucleotide Polymorphisms).
These are
usually designated as +4643Rsa1 or +11329Alu1 etc as you have pointed
out in
your messages.
Vincent's classification on the website and in the papers you refer to
contain a complete list of these variants. What they mean is that a
restriction enzyme recognises the variation and either cuts or does
not cut
the DNA at that point. Since your hobby is reading about DNA I am
sure I
don't need to explain what a restriction enzyme is. So, take
+4643Rsa1. That
means the enzyme Rsa1 cuts at base number 4643. The variant -4643Rsa1
means
that the enzyme does not cut the DNA.
Vincent and I, with Martin Richards, spent a great deal of time
correlating
the control region variants with the SNPs by analysing both on several
hundred (it may even have been thousands) of mtDNAs and this was an
important part of distinguishing the different clans. On the whole
these
types of variant are more stable than some of the control region
sequence
variants but not always and ideally every DNA should be tested for
both.
However, that would put the price to customers up hugely because each
one of
the SNPs had to be done separately - although I know that Oxford
Ancestors
are looking into offering this service.
But even that would not guarantee completely accurate assignment in
every
single case. Only sequencing the entire mtDNA circle of sixteen and a
half
thousand bases at astronomical cost would do that - though even that
would
not be any good unless you had at your fingertips a database of
thousands of
other complete sequences with which to compare it and only a handful
have
been completely sequenced to date. Also, as more work is reported, the
evolutionary networks will change.
What I am getting at is that no system is foolproof. The Oxford
Ancestors
service, to keep it affordable, only sequences the control region.
Then the
sequence is compared to a database which holds other sequences which
have
been examined for SNP variants. If the customers control sequence
matches up
with one of these then it is assigned to the same clan. In other
cases,
where there is not an exact match, the database is searched for close
matches or sites which are characteristic of particular clans. In the
case
of your sequence which has variants from the reference sequence at
189, 356,
362 (we delete the 16 prefix for HVS1) two of the three variants are
quite
unstable - that means they can mutate back and forth. Position 189 is
one of
the least stable of all and 362 is not very far behind. Position 356
is far
more stable and is also characteristic of clade U4, whose clan mother
is
Ulrike. However, it is not completely stable and does crop up in other
clans
- one of which is Helena.
So the sequence 189, 356, 362 could be in the clan of Ulrike mutating
at the
unstable positions 189 and 362 away from the U4 root sequence of 356.
Or it
could be in the clan of Helena with a rare variant at 356 taking it
away
from 189, 362. One way of telling the two apart is to look at the
variant at
073. This is actually in HVSII and not HVSI and that was a source of
confusion in some of the email exchanges I have read. Oxford Ancestors
doesn't do the 073 test, as you know, so the sequence was assigned on
the
balance of probabilities to Ulrike. I have now had a chance to compare
the
sequence to some new research data of my own from Britain in which we
did do
the 073 test and found five exact matches which carry A at 073,
indicative
of clade H. So I think you are probably correct and are indeed a
daughter
of Helena rather than Ulrike. This means that the mutation at 356
would have
occurred on a Helena background rather than the 189 and 362 variants
occurring on a Ulrike background.
That might explain why you were originally issued with a Helena
certificate
in August 2000. At that time, the service was being sent out from my
laboratory before Oxford Ancestors acquired its own premises. That
means
that whoever did that first assignment, and it may well have been me,
did
recognize the ambiguous nature of the 356 mutation in that particular
sequence but that piece of information was not properly transferred
to the
new set-up - and that is my fault.
I must thank you for clarifying the assignment of this particular
sequence.
It is a changing field and your observation has helped it move on one
more
stage further. I am sure Dr Ashworth will want to issue a new Helena
certificate. And of course, I hope you are pleased to have moved back
to
your original clan.
Yours sincerely
Bryan Sykes MA PhD DSc
Professor of Human Genetics
University of Oxford
Dolly Ziegler
Roots 7th edition relates to your soon-to-be-published Plantagenet
Ancestry III. Can't locate the post which outlined your plan for -- three
volumes, replacing AR7, Magna Charta Sureties 4 and Plantagenet Ancestry?
I'd appreciate a brief outline of your plan, and am posting to the list
because it will interest many others.
Please do not take too much time on your reply, though, because I do not
want to take a minute from preparations for PAIII, which I eagerly await.
;-)
Cheers, Dolly in Maryland
Gordon Banks
DNA work is for practical genealogy of most of us. These (7 women)
ancestors lived many millenia ago, if my understanding is correct.
The research on the Y chromosome is of more direct interest, and there was
an article on it in New England Ancestry this month. Since the male gets
the Y from his father, and the father from his father, it is a way of
determining relationships between male lines of the same surname. Genetic
studies in humans have revealed about a 10% level of "female infidelity": in
other words, the offspring not being the genetic offspring of the husband.
This directly impacts genealogy, and provides an element of uncertainty into
the most carefully documented pedigree. If a database can be built of
documented male lines, such "anomalies" could be uncovered. The question
is, who is going to spend the money to do this? (Those interested in rates
of and reasons for female infidelity might be interested in a book called
"The Myth of Monogamy.")
Ian Cairns
news:MCEMJEDENIHEFICCL...@gordonbanks.com...
New Scientist - a reputable popular scientific weekly - has the
following article which may affect the above laws...
http://www.newscientist.com/news/news.jsp?id=ns99992716
(full sources given in the article)
Regards
Ian
Douglas Richardson
The final manuscript of Plantagenet Ancestry is nearing completion.
I've started sending out parts of the manuscript for proofreading.
Work has commenced on the bibliography. The individual family
accounts have finally been joined together into a master document.
The page count of the master document is currently running a whopping
840 pages, excluding the introduction, bibliography, and index.
I could drastically cut the manuscript to trim down the page count.
However, my feeling is that the information I collected is what people
want. So, other than possibly alter margin settings, the final book
will almost certainly run 900 plus pages. Since I was anticipating
something about 300 pages less, needless to say, I find it necessary
to raise the prepublication price of the book from $60.00 to $65.00
(domestic orders), and from $65.00 to $70.00 (foreign orders). Also,
effective immediately, a postage and handling charge of $3.00 per book
will be assessed. If anyone wishes to buy a copy of the book, they
may contact me at my e-mail address below.
I presently anticipate being completed by January 1st. This is an
estimated finish date which may fluctuate due to several factors, some
of which are not under my control. As for the manuscript itself, as
each of the various accounts are finished, they're looking super. I'm
sure everyone will be very pleased with the completed Plantagenet
Ancestry book.
In answer to Dolly's specified question, the Plantagenet book is the
first of several planned volumes in a series entitled Royal Ancestry
Series (RAS). The other volumes will include a Magna Carta volume, a
Baronial volume, and a Carolingian volume. I'll discuss my plans for
the other volumes at a later date.
Best always, Douglas Richardson, Salt Lake City, Utah
E-mail: royala...@msn.com
s...@bcpl.net (Dolly Ziegler) wrote in message news:<Pine.GSO.4.44.0209151310250.7274-100000@mail>...
Dolly Ziegler
> ...So, other than possibly alter margin settings, the final book
> will almost certainly run 900 plus pages.
Thanks for the update, Doug. This gives me about 3 1/2 months to reinforce
my bookcase. ;)
Cheers, Dolly in Maryland (no reply required)
Douglas Richardson
Thanks for your sense of humor. Much appreciated.
Since answering your post, several people contacted me by private
e-mail today. They had earlier ordered the Plantagenet Ancestry book
at the lower price and asked if they needed to send more money. The
price increase is effective for new orders as of today. If anyone
paid for the book at the lower price prior to today, that price will
be honored.
Now if I can just find a way to shrink the manuscript ...
Douglas Richardson, Salt Lake City, Utah
d...@bcpl.net (Dolly Ziegler) wrote in message news:<Pine.GSO.4.44.0209161350470.6807-100000@mail>...
L Mahler
future issues of TAG.
Leslie
ttg1313
norenxaq
Douglas Richardson wrote:
> Dear Dolly ~
>
> Thanks for your sense of humor. Much appreciated.
>
> Since answering your post, several people contacted me by private
> e-mail today. They had earlier ordered the Plantagenet Ancestry book
> at the lower price and asked if they needed to send more money. The
> price increase is effective for new orders as of today. If anyone
> paid for the book at the lower price prior to today, that price will
> be honored.
>
> Now if I can just find a way to shrink the manuscript ...
simple....
microfilm :>
Doug McDonald
norenxaq wrote:
>
> >
> > Now if I can just find a way to shrink the manuscript ...
>
> simple....
>
> microfilm :>
The manuscript is not the problem ... it surely will fit on one
CD.
The problem is the hard copies.
Doug McDonald