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DNA data - how useful is it realy?

R M Bernstein ralph at ccit.arizona.edu
Sun Sep 3 12:55:55 EST 1995

In Article <42bdfc$jam at ns1.usa1.com>, suihuang at usa1.com (suihuang at usa1.com)

>SEQUENCING THE GENOME   is just what HAS to be done - not more. 
>As we have the technology to do it, we have the moral duty to 
>do it. But Ludwig Mortenberg is right: knowing the sequence of 
>the genome is of little scientific value in terms of 
>UNDERSTANDING the complexity of life. Even if we knew all 
>genes, their structures and which gene intereacts with which 
>one, we wounldn't be able to understand ontogenesis, 
>pattern formation, differentiation and lastly (as a price that 
>we pay for differentiation) oncogenesis. Too much focussing on 
>the linear task of genome sequencing will lead to neglecting 
>NON-linear thinking. NON-linearity is the key issue of all 
>emergent properties such as LIFE itself.
>The one-gene --> one phenotype paradigm, on which the HUGO 
>project is based cannot explain the complexity of living 
>>Sui Huang

ahhrg Sui, i cry foul.  How can you beleive this?  You say "knowing the
sequence of the genome is of little scientific value in terms of
UNDERSTANDING the complexity of life"!!  Ahhrg!
    look , one of the most simple examples of how the sequence is CRUCIAL to
the understanding of the complexity of life may be lost on
non-immunologists..  the rearranging immune system is absolutely INCREDIBLE.
Just the simple 300bp IG (or immunoglobulin) domain alone has been
duplicated and mutated to form and or give rise to a myriad of incredible
molecules that have may have allowed for the absolute success of vertebrates
as a whole.  the vertebrate type ImmuneResponse- only seen in vertebrates,
hence the name- has allowed vertebrates to respond to foreign antigens
(immune system) AND respond to self (development).  the complexity of life,
and the successfulness of certain life forms -in some ways- can be "rated"
on their possession of Ig domain containing molecules.  and they have not
all been cloned yet! (sorry, bad grammer)  these molecules are being
discovered all the time.  
    the b7-1 and b7-2 and cd 28 ctla-4 system are IG related, the surrogate
alpha chain is IG related, CD-4 (the gp120, HIV target) is IG related, (list
goes on and on) and these are some the most important things in cellular
immunology right now. 
     the gene sequences alone that make up ig genes are central to
understanding the complexity of life.  why does every vertebrate organise
their ig genes completely differently?  and why do their RAG or recombinase
activating genes and other recombination activating system still function
properly?  some organisms have "fused" V and D gene segments.  some have
fused VDJ segments. some have a mixture, and some have them completely
isolated, able to recombine freely.-more to the point: how do these gene
arrangements affect the organisms fittness, and therefore contribute to the
understanding the complexity of life.

    you say we won't be able to understand  "ontogenesis,  morphogenesis, 
>pattern formation,  differentiation and lastly (as a price that we pay for
differentiation) oncogenesis.)"  

    come on, gene segments and the order of nucleotides may seem
un-interesting to you, but things as specific as oncogenesis are right there
in the genes...look at what causes cancre...i ve read recently in science
that upto ~90 % of cancres come down to dna repair defects, so a problem in
the machinery that stops cells from cycling, eg p53, the ataxia gene, and
that repairs the damaged dna eg human MUT homologues, exinucleases, etc etc
etc.   these genes get damaged and they can no longer cause the apoptosis of
damaged cells, or even stop thoses cells from incorporating the damaged
bases, lesions, etc from being incorporated into that cell's genome.  that
is oncogenesis.  a result is cancres from overproductive genes, termed
"oncogenes" by the nifty.  these are the result of repair and stop gap gene
products gone wrong.  the sequence of the damaged genes was ESSENTIAL in
understanding where the cells went bad.  can you see this?  

    look, i am not working on the "linear" gene sequencing project.  you are
(presumably) not working on the "linear" gene sequencing project.  the
majority of scientists are not working on the "linear" gene sequencing
project.  you may be upset at the amount of money being spent on this, but
it is a one time thing.  if a greater understanding of the complexity of the
genome is gained by this, them i feel that it is a completely valid project.

regards, ralph

Ralph M. Bernstein
Dept of Micro/Immuno
University of Arizona
Ph: 602 626 2585
Fx: 602 626 2100
url: http://lamprey.medmicro.arizona.edu

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