Re: Moorad's comment is sound

On 6/29/05, RFaussette@aol.com <RFaussette@aol.com> wrote:
>
> In a message dated 6/25/2005 5:25:07 PM Eastern Standard Time,
> rich.blinne@gmail.com writes:
>
> All Cochran did was present an unproven hypothesis (which he readily
> admits). I'll close with what a properly-designed study
> <http://http://www.nature.com/nature/journal/v405/n6788/full/405847a0_fs.html>(that at least has a control) looks like to resolve this question:
>
> *Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease
> in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis.
>
> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14727180&query_hl=14>
> Frisch A, Colombo R, Michaelovsky E, Karpati M, Goldman B, Peleg L.*
>
> Felsenstein Medical Research Center, Rabin Medical Center, 49100, Petah
> Tikva, Israel. afrisch@post.tau.ac.il
>
> The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene
> mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage
> diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews
> (AJs). To investigate the genetic history of this mutation in the AJ
> population, a conserved haplotype
> (D15S981:175-D15S131:240-D15S1050:284-D15S197:144-D15S188:418) was
> identified in 1278insTATC chromosomes from 55 unrelated AJ individuals (15
> homozygotes and 40 heterozygotes for the TSD mutation), suggesting the
> occurrence of a common founder. When two methods were used for analysis of
> linkage disequilibrium (LD) between flanking polymorphic markers and the
> disease locus and for the study of the decay of LD over time, the estimated
> age of the insertion was found to be 40+/-12 generations (95% confidence
> interval: 30-50 generations), so that the most recent common ancestor of the
> mutation-bearing chromosomes would date to the 8th-9th century. This
> corresponds with the demographic expansion of AJs in central Europe,
> following the founding of the Ashkenaz settlement in the early Middle Ages.
> The results are consistent with the geographic distribution of the main TSD
> mutation, 1278insTATC being more common in central Europe, and with the
> coalescent times of mutations causing two other LSDs, Gaucher disease and
> mucolipidosis type IV. Evidence for the absence of a determinant positive
> selection (heterozygote advantage) over the mutation is provided by a
> comparison between the estimated age of 1278insTATC and the probability of
> the current AJ frequency of the mutant allele as a function of its age,
> calculated by use of a branching-process model. Therefore, the founder
> effect in a rapidly expanding population arising from a bottleneck provides
> a robust parsimonious hypothesis explaining the spread of 1278insTATC-linked
> TSD in AJ individuals.
>
> I had been collecting the threads from the evopsych list to respond to you
> and I was just going to send them and I can't find them, I might have
> deleted them in error, but when I considered collecting them again, I
> noticed you copied Burgy and I remembered his inappropriate response to me
> at the beginning of this thread and I decided I'm not going to argue the
> point anymore. You completely ignored every quote I offered from prominent
> Jews who admitted self selection even using the word as Metzenberg did. You
> have responded only to the genetics argument which made the proper
> connection between the high intelligence and the genetic diseases but you
> fail to see the self selection process, even harpending failed to see it
> when he assumed there was selection pressure on intelligence on only the 1%
> of the communities who were rabbis.
>
  My point is that the so-called connection between intelligence and genetic
diseases does not follow. That's because genetic drift rather than
heterozygote advantage best explains the genetic diseases. Since my original
bounced to this list, I will also note that Tay Sachs also shows founder
effects in Iraqi and Moroccan Jews as well as French Canadians and
Accadians. What all these communities have in common are isolation and
bottlenecks that are the markers for the founder effect and not rigorous
self-selection. For example Lithuanian AJ showed different Tay Sacks alleles
and the allele ages from Central European ones. The allele ages for a given
locale were similar across both the LSDs and non-LSDs. As noted by Risch,
this clustering of diseases is probably the result of selection bias. That
is, we see LSD disease and thus we look for the genes of other LSD diseases.
Furthermore since LSD is lethal the defect is more noticeable. Risch
predicts that we will probably see the same for cancer in AJ given that we
see BRCA defects in AJ. Given no heterozygote advantage (Cochran noted that
it is possible that there is no heterozygote disadvantage either.) there is
no need to explain the selection pressure. No effect. No need to have a
cause.
  
> When you're ready to consider the data I've presented and not just the
> data you present, we'll have a thread. Until you acknowledge that Jewish
> torah scholars of yeshiva university themselves write that Jews self select
> you're just out there in la la land ignoring what doesn't fit your world
> view.
>

When you're ready to consider the data I've presented and not just the data
you present we'll have a thread. Until you acknowledge that a non-existent
effect requires no cause you're just out there in la la land ignoring what
doesn't fit your world view. BTW, what is my world view and how does it
affect this discussion? Hint: think epistemology.
Received on Wed Jun 29 15:39:22 2005