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Baker Street Irregulars
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We now have an unimaginably huge
amount of information about the human
genome: a pretty good sequence,
annotated with features that include
genes, regulatory elements, variant
sequences and much much more (see
Interpreting it, however, is much harder.
It's a huge
mass of information, and
the interesting stuff is very subtle and
hard to spot. A typical example is trying
to find which particular genomic
may predispose you toward depression,
make it more likely that your children will
have big ears.
As the analyses get ever more complex
and subtle, we are slowly getting bogged
I therefore propose that we add I Ching
annotations to the genome. There are
codons (DNA "words" - each made of
DNA letters), from AAA through to TTT.
By an odd coincidence, there are 64
hexagrams in the I Ching, each with its
own meaning. It is a simple matter,
therefore, to map the one onto the other.
To take a very simplistic example, the
gene coding for normal beta globin (part
of haemoglobin) contains the following
sequence "..CTG ACT CCT GAG
GAG..." (coding for amino acids leucine,
threonine, proline, glutamic acid,
acid, as part of the protein). According
the I Ching, and numbering the codons
through TTT as 1-64 respectively, this
Clearly this is a good protein to have.
beta globin molecules join together (the
protein is tetrameric - two betas and two
alphas), and blood circulates freely
(returning to the heart after passing
through the fine capillaries of the lungs
tissues), enabling the person to prosper.
The most common mutation causing
sickle-cell anaemia is a change of an "A"
to a "T", so the sequence runs: "..CTG
CCT GTG GAG...". As a consequence, the
first of the two glutamates becomes a
valine. With the I Ching at hand, though,
we can see that the first
"Prospering" (hexagram 35, GAG) has
46, GTG). Clearly, ascending is not
something you want your blood to do.
Of course, more rigorous rules need to
worked out to establish a logical
between the I Ching and DNA sequence.
For example, regulatory sequences in the
genome don't come in three-letter
"words", so their I Ching meaning will be
harder to establish.
However, once this is done by a
concerted effort amongst
bioinformaticians, we will find
the genome much more amenable to
interpretation. Complex polygenic traits
might suddenly become easier to spot
amongst the mass of A,C,G and T.
Perhaps your predisposition to obesity is
because you've got alleles which
give you Great Accumulating in one
protein in a key metabolic pathway, and
Great Exceeding in a second enzyme in
A small piece of your genome
Shows some of the information on one small part of the human genome. The Ensembl genome broswer is already configured to display many different types of annotation to the sequence. I Ching would be easy to add. [MaxwellBuchanan, Sep 21 2007]
||Sorry, but making sequence data four times longer isn't going to help me.
||What does help me is making little word sounds out of the segment I am searching for, and repeating that in my head while I look: Cat tuh tuh Gaaat tuh Kag (CATTTGAATTCAG)
||PS what you call a coincidence I call four to the third power.
||Trust me, Cat tuh tuh Gaaat tuh Kag
breaks down over a megabase. And the I
Ching will do as good a job of throwing up
candidate genes as most of the current
association studies are doing.
||Well, a three-times-longer system breaks down three times faster. I was trying in my head to come up with a more useful system than the current one, and all I could come up with was renaming the amino acids. The current names are hard to remember and only slightly descriptive.
||Maybe call them by their side group, followed by "aminoacid".
||So Hydrogenaminoacid, Methanaminoacid, isobutanaminoacid, phenylmethanaminoacid, etcetera.
||Way too sensible. Shirley much more
inspiring, for example, to have the
genome decorated with annotations such
as "SNP 23998: minor allele freq 0.3;
Centre confirming -> Small exceeding."
||could I just read your palm before I try to make sense of this?
||you have 16 children? did you know?
||does the name Fred mean anything to you? she is standing behind you - waving rubber gloves, saying "latex, honey?"
||I think you may be confused by the fact
that my palm was recently re-potted. I
believe that can affect the interpretation.
||I prefer an iPAQ over a palm, as it comes with its own built-in reader. It's bulk in my pocket though has been known to cause some i-tching.
||Buchanan: Don't give up on this I Ching,
genome thing - that's what spreadsheets
and terabytes are for!
||There may be 64 codons, but there's only 20 amino acids in the standard translation . If you also count 'stop', thats 21.
Changing which of the several codons encodes an amino acid usually has little effect.
other amino-acids can be inserted in a template-directed manner under certain very rare conditions. See - selenocysteine, pyrolysine.
||//Changing which of the several codons
encodes an amino acid usually has little
effect.// (a) not necessarily true and (b)
not necessarily relevant.
||(a) Most organisms have a strong codon
bias, preferring only one or two of the
possible codons for a given amino acid.
This strongly affects translation rates.
||(b) there are many instances where you
want to represent the DNA sequence,
not just the amino acid sequence. For
example, any time you want to
manipulate DNA (restriction digest,
PCR, probes, arrays..) you need the
||"...Conjoining- Grouping- Returning- Prospering- Prospering..." actually makes a neat little cult chant when your read it out loud.
||Exactly. And patients will be so much
more at ease if, instead of saying
"You've got an A/T substitution in
codon 4 of your beta globin", you can
calmly say "We believe that your
problem is due to an Ascending where
you should be Prospering".
||Genetic diseases could likewise be
renamed in more comfortable terms.
You haven't got DMD, you've got
Sprouting disease. No longer will you
suffer from Huntingdon's disease, you'll
just have too many Great Possessings.
||Bioinformaticians will suddenly become
calm, wise people - for the first time.