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Archiver > GEN-MEDIEVAL > 1997-07 > 0870112007


From: "D. Spencer Hines" <>
Subject: Re: George Rex
Date: Mon, 28 Jul 1997 07:46:47 -1000


Todd A. Farmerie wrote:
>
> C. Mason wrote:
> >
> > > (Except for the cases in which a female suffers from it, having gotten
> > > the nasty gene from both parents.)
> > >
> >
> > It is my understanding that NO female has suffered from hemophelia. [sic]
The
> > recessive gene is carried thru the female line and the disease manifests
> > itself in her male offspring. It would appear that Victoria passed the
> > genetic propensity to her female offspring thru the third generation.
>
> While it most commonly occurs in men, it can occur in women. Almost all
> hemophelias [sic] (hemophilias) are caused by the lack of a good copy of the
gene for one of
> the blood clotting factors, in this case Factor VIII. This gene is
> located on the X chromosome. Since men are XY, then if their X has a
> bad copy, they don't have any good copies. Women are XX, and thus they
> can be carriers. The deficience of their bad copy is compensated for by
> the other good copy of the gene, and they have essentially normal
> clotting. If, however, both of their X chromosomes are bad, then they
> have no good copies.
>
> Why these cases are rare is due to simple statistics,

[Not so simple, if we are working with imaginary numbers]

> and also until
> recently, for epidemiological reasons. If the frequency of mutant FVIII
> genes in the human population is 1 in 2000 (this is not the true value,
> but will demonstrate the point)

What is the *true* value, rather than an imaginary value? It would make
the point much better to be working with accurate numbers ---- rather
than just with a swag.

> then one in 2000 men will suffer from
> it. For a woman to suffer, both must be bad, in other words, 1 in 2000
> for each X, or 1 in 4,000,000. Thus there would be 2,500,000 male
> sufferers on the planet, and only 1200 females (statistically
> speaking).

The numbers quoted above do not have any real meaning, do they ----
because they are based on a guess [1 in 2000]? So, statistically
speaking, these numbers of 2,500,000 and 1200 are purely imaginary. We
need to start with a *true* value or good estimate for the frequency of
occurrence of mutant Factor VIII in the human population --- and clearly
eliminate any of the other blood clotting factors from consideration.

>
> The epidemiologic reasons are due to the facts of its inheritance. For
> a female to have 2 bad Xs, she must have gotten one from her father.
> That means that (except for the case discussed below of a spontaneous
> germ-line mutation) the father must have been a hemopheliac, [sic]
(hemophiliac) since his
> one X must then have been faulty. Prior to modern medicine, many
> (most?) hemopheliacs [sic] would have bled to death before reaching maturity,
> and passing on their mutant gene. If all hemopheliacs [sic] bled to death
> before reproducing, there could be no female sufferers. Modern medicine
> would allow reproduction, and thus passing on of the gene by males, and
> will doubtlessly increase both the number of female sufferers, and the
> total proportion of the mutant gene in the population (it will only get
> worse).
>
> > I also have NEVER heard of it being a symptom caused by the age of the
> > parents at gestation. If you have sources for your statments please
> > forward them.
>
> I was not refering [sic] to hemophelia [sic] specifically, but to the
mutational
> process in general. With no known occurance [sic] in the generations prior
to
> Victoria, it is reasonable to conclude that the mutation initiated in
> one of her parents (or perhaps in her mother's parents, Victoria being
> an only child). Her father immediately comes to mind, because of his
> age at her birth. It is well known that the probability of birth
> defects begins to increase dramatically as the father ages (and
> particularly after 45 or so), and a recent study looked at DNA mutations
> themselves, and saw the same thing. (I could go into the mechanism for
> this if you would like.)

Aththough I do not doubt the accuracy of your tentative speculative
statements in the paragraph, supra ---- it would be useful to have the
citations for your sources, as C. Mason requested ---- and the names and
credentials of the researchers involved. Just saying, "a recent
study...saw the same thing" is not very helpful --- however it is good,
un-documented, authority-rattling.

> It is thus extremely likely that the mutation
> in the FVIII gene which Victoria passed on to her descendants was the
> result of a germ cell mutation in the immediately prior generation, and
> somewhat more likely that it was in her father, since he demonstrates
> one strong risk factor, than that it was in her mother or maternal
> grandparents.
>
> taf

When a correspondent consistently misspells the name of the disease that
he is trying to explain ---- it tends to undercut the credibility of his
response.
--

D. Spencer Hines---Lady Astor, nee Nancy Langhorne of Danville,
Virginia---first woman to serve as an MP---[Conservative, Plymouth]---a
Teetotaller, Appeaser and Ardent Francophobe; at a dinner party with
Winston Leonard Spencer Churchill (1874-1965): "Winston, you're drunk!"
WLSC: "Yes Madam, I am---and you are ugly. But tomorrow, I shall be
sober---and you will still be ugly."

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