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Author Topic:   Alleles at the amino-acid/SNP level? Any experts out there?
Tranquility Base
Inactive Member


Message 1 of 14 (13955)
07-22-2002 9:29 PM


Here is a link on the basics of alleles (as the source of biological traits) for the uninitiated: http://www.borg.com/~lubehawk/multalle.htm

Here are some questions for the experts:
------------------------------------------------

1. Does anybody out there know some examples at the SNP (single nucelotide polymorphism) and amino-acid level?

2. Something I have wanted to know for years - blue/brown eyes - what are the allele amino-acid sequences/differences/SNP(s)?

3. Do allele's differ trivially or by many amino-acids?

4. What patterns are there? Two alleles seems to be very common but is this just in the simplified dominant/recessive case?

5. Of course there are lots of SNPs which don't have a clear phenotypic trait. Are these referred to in some special way?

It relates to CvsE but I'm also just plain interested.

[This message has been edited by Tranquility Base, 07-22-2002]


Replies to this message:
 Message 2 by Fred Williams, posted 07-23-2002 1:29 AM Tranquility Base has responded
 Message 3 by Peter, posted 07-23-2002 3:35 AM Tranquility Base has responded
 Message 4 by peter borger, posted 07-23-2002 5:24 AM Tranquility Base has responded

  
Fred Williams
Member (Idle past 3412 days)
Posts: 310
From: Broomfield
Joined: 12-17-2001


Message 2 of 14 (13976)
07-23-2002 1:29 AM
Reply to: Message 1 by Tranquility Base
07-22-2002 9:29 PM


I’m not an expert, but I do know the answer to most of these…

quote:
1. Does anybody out there know some examples at the SNP (single nucelotide polymorphism) and amino-acid level?

Sickle-cell for one.

quote:
2. Something I have wanted to know for years - blue/brown eyes - what are the allele amino-acid sequences/differences/SNP(s)?

Hmm. I’d like to know too.

quote:
3. Do allele's differ trivially or by many amino-acids?

Can be one or many. Allele typically refers to something recognized by its phenotypic effect.

Technically, a synonymous mutation (no new amino acid selected) would qualify as an allele, but would more accurately be called a haplotype.

quote:
4. What patterns are there? Two alleles seems to be very common but is this just in the simplified dominant/recessive case?

The latest number I've seen is that an individual human runs about 6.7% heterozygous. So, the majority of loci are homozygous (1 allele only)

quote:
5. Of course there are lots of SNPs which don't have a clear phenotypic trait. Are these referred to in some special way?

Haplotype.


This message is a reply to:
 Message 1 by Tranquility Base, posted 07-22-2002 9:29 PM Tranquility Base has responded

Replies to this message:
 Message 5 by Tranquility Base, posted 07-23-2002 7:25 AM Fred Williams has not yet responded

  
Peter
Member (Idle past 35 days)
Posts: 2161
From: Cambridgeshire, UK.
Joined: 02-05-2002


Message 3 of 14 (13984)
07-23-2002 3:35 AM
Reply to: Message 1 by Tranquility Base
07-22-2002 9:29 PM


quote:

4. What patterns are there? Two alleles seems to be very common but is this just in the simplified dominant/recessive case?

You also get co-dominance, where there are more than two alleles
(e.g. ABO blood groups, coat colour in cattle). In this
case the heterozygous phenotype is different from either
homozygous one.

I believe that even with eye-color the dom/rec model is simplified
because we also have grey, green, amber, hazel, etc. eye
colors.


This message is a reply to:
 Message 1 by Tranquility Base, posted 07-22-2002 9:29 PM Tranquility Base has responded

Replies to this message:
 Message 6 by Tranquility Base, posted 07-23-2002 7:28 AM Peter has responded

  
peter borger
Member (Idle past 6222 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 4 of 14 (13988)
07-23-2002 5:24 AM
Reply to: Message 1 by Tranquility Base
07-22-2002 9:29 PM


Dear TB,
Interesting questions and I have given them a thorough thought for many years.
Fred already responded to the major part and I will respond to:

"2. Something I have wanted to know for years - blue/brown eyes - what are the allele amino-acid sequences/differences/SNP(s)?"

The genetics of eye colour of humans is pretty intricate. It cannot be explained by the application of simple Mendelian genetics. It is more likely that epigenetics determines the differences in colour.

Ever met a person with two distinct eye-colours (eg David Bowie)? In my opinion this can best be explained by epigenetics (=beyond genes). It is known that every individual has several alleles for eyecolour (in fact eye colour genes are completely redundant since they serve "no" function). The expression of the genes that determine the ultimate colour are stringently regulated. The regulation of genes strongly depends on DNA elements in the vicinity of the gene. On has to imagine the DNA spatially; elements within 10-100 kb can easily affect the expression of the genes because of spatial folding of the DNA molecule. In this way, transposable DNA elements are able to affect eyecolour. These elements are thought to be (retro)transposons and Alu-sequences. I think it will soon be discovered that these sequences -- that have always been regarded as junk DNA -- have a crucial function in generating the differences within species. In contrast to what everyone beliefs (=paradigm), I belief that genes -- although the contribute -- do not determine the phenotype of an organism. Gene expression and (thus gene regulation) does!!!!

Best wishes,
Peter


This message is a reply to:
 Message 1 by Tranquility Base, posted 07-22-2002 9:29 PM Tranquility Base has responded

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 Message 7 by Tranquility Base, posted 07-23-2002 7:35 AM peter borger has not yet responded

  
Tranquility Base
Inactive Member


Message 5 of 14 (13993)
07-23-2002 7:25 AM
Reply to: Message 2 by Fred Williams
07-23-2002 1:29 AM


Thanks Fred - I'm familiar with sickle cell anemia (Val 3 I think??). Thanks for Haplotypes. I'd love to see the sequences of some real alleles. Of course the human genome did this and found lots of SNPs which form the basis of alleles. I'd love to see some classic and characteristic cases studies.

This message is a reply to:
 Message 2 by Fred Williams, posted 07-23-2002 1:29 AM Fred Williams has not yet responded

  
Tranquility Base
Inactive Member


Message 6 of 14 (13994)
07-23-2002 7:28 AM
Reply to: Message 3 by Peter
07-23-2002 3:35 AM


Thanks Peter - Yes, I've heard a lot of these words over the years and would love to see it reframed in the language of genomes and SNPs. (I study structural genomics and rarely think about SNPs). I wonder if the blood groups come down to three alleles (or even 3 SNPs) for example?

This message is a reply to:
 Message 3 by Peter, posted 07-23-2002 3:35 AM Peter has responded

Replies to this message:
 Message 8 by Peter, posted 07-23-2002 10:51 AM Tranquility Base has responded

  
Tranquility Base
Inactive Member


Message 7 of 14 (13995)
07-23-2002 7:35 AM
Reply to: Message 4 by peter borger
07-23-2002 5:24 AM


Thanks Peter B - Even though most traits will be governed by more than just one gene it is probably still the case that many traits can be said to be single gene at first order. I picked eye color because it is well known and is to a fairly good extent true. Anyway there are lots of approximately dominant/recessive traits that probably have only two major alleles in the population. I would love to see what their amino-acid seqeunces are! Similarly for traits governed by more than two alleles or more than one gene. But simple is easier at the start.

[This message has been edited by Tranquility Base, 07-23-2002]


This message is a reply to:
 Message 4 by peter borger, posted 07-23-2002 5:24 AM peter borger has not yet responded

  
Peter
Member (Idle past 35 days)
Posts: 2161
From: Cambridgeshire, UK.
Joined: 02-05-2002


Message 8 of 14 (14003)
07-23-2002 10:51 AM
Reply to: Message 6 by Tranquility Base
07-23-2002 7:28 AM


http://www.biotechinstitute.org/pdf/Vol_9_1_2pg.pdf

Has a snip of information on this. It would appear that
the O allele has a G missing.

http://www.artsci.wustl.edu/~jstader/Dickinson.htm

Also says that ::

"the gene encoding A, B, or O blood type can differ by four single nucleotide
polymorphisms. If the gene contains the sequence CGTGGTGACCCCTT, then it will produce antigen A. Antigen B is
produced by the same gene when four SNPs are inherited from a parent. In this case, the gene contains the sequence
CGTCGTCACCGCTA. When this gene encodes type O blood, it has the sequence CGTGGT-ACCCCTT. This
sequence differs from that of the A antigen by one base deletion, which is indicated by the dash. The result of this deletion
is a shift in the reading frame and a gene that produces no antigen at all (Czarnik, 1998)."


This message is a reply to:
 Message 6 by Tranquility Base, posted 07-23-2002 7:28 AM Tranquility Base has responded

Replies to this message:
 Message 9 by Tranquility Base, posted 07-23-2002 9:10 PM Peter has responded

  
Tranquility Base
Inactive Member


Message 9 of 14 (14028)
07-23-2002 9:10 PM
Reply to: Message 8 by Peter
07-23-2002 10:51 AM


^ Nice Peter. You win the prize!

I'll have to read those sites.

Unfortunately we can't be sure that these DNA segments are 'in frame' becasue for a start they aren't multiples of three. Being a protein person (which is the business end of gene function) I want to translate those sequences into amino-acids.

Summary

CGTGGTGACCCCTT Antigen A
CGTCGTCACCGCTA Antigen B
CGTGGT-ACCCCTT Antigen O

I'll try and find out if these are exonic. O is a frame shift and obvioulsy causes the protein fragment to not translate or not fold.

I don't want to sidetrack too much away from the fascinating basic science here, but, from a creationist POV I would like to suggest that these SNPs are easy to imagine occurring in a short time even if there was only one initial allele. I would also suggest that the protein fold would be unchanged (the full gene would be probably be thousands of bases long) except for O where it is either unexpressed or doesn't fold. From a genomic/structural biology POV alleles are just varieties of a protein and as such, if still functional, wold be expected to have the same protein fold.

Does anybody know what phenotype OO people have? This gene may be semi-redundant but it's conservation suggests it is not completely redundant.

Note that O is essentially identical to A but with a frameshift causing lack of expression or folding. So blood type can be thought of as having 2 functional alleles and 1 non-functional.

PS - if they are in frame, and exonic, then the amino acid sequences of the first 12 bases is:

RGDP A
RRHR B
RGTP O (with the rest frameshifted including the stop codon)

The seqeunce of B is quite different from A. R =Arginine is very diff to G=Glycine. D=Aspartic Acid is charged as is H=Histidine. P=Proline is very diff to R=Arginine.

Note that the remaining hundreds of amino-acids of A and B will be identical and hence the proteins almost definietely have the same fold. The functions of A and B would have near identical functions and the primary difference is probably in immunological reactions due to antibody binding to these proteins.

[This message has been edited by Tranquility Base, 07-23-2002]


This message is a reply to:
 Message 8 by Peter, posted 07-23-2002 10:51 AM Peter has responded

Replies to this message:
 Message 10 by Peter, posted 07-25-2002 4:30 AM Tranquility Base has responded

  
Peter
Member (Idle past 35 days)
Posts: 2161
From: Cambridgeshire, UK.
Joined: 02-05-2002


Message 10 of 14 (14118)
07-25-2002 4:30 AM
Reply to: Message 9 by Tranquility Base
07-23-2002 9:10 PM


Is there a way of knowing for sure that O comes
from a deletion, rather than A coming from an insertion
and B from a copy error of A ? (or A a copy error of B)

Or is this all guesswork at this level ?

As i understand it, it was formerly believed that O came first,
but now that A was first (there's a link lower to some
work on this).

OO has type O blood (like me) is that what you meant ?

http://www.er4yt.org/Education/Science_A2_Subtype.html

I think it tends to suggest that dominant/recessive model is likely
somewhat of a simplification though.

I also found this ineresting (although I don't agree with
the conclusions)::
http://www.lexiline.com/lexiline/lexi9.htm

Don't know much about the site itself, so checking up on the
data it presents ... but ...

It concerns primate blood groups and says that Chimps have A and O
blood types, but no B, while Gorillas have B and O but no A.

It also says that the earliest (supposed) human ancestral remains
are found in an area of africa where chimp and gorilla territories
overlap.

Other mammals (felines, canines, equines, etc.) do not have an
ABO blood type system (although cats have an AB system that is
somewhat similar, although the co-dominance is not apparent).

To me this says that there is some direct ancestral relationship
between man, chimps and gorillas. Common design seems less likely
since only the primates seem to have this blood group.

Perhaps man is the missing link between chimps and gorillas

This site:: http://www2.justnet.ne.jp/~shozo_owada/saitou-e.htm

Actually is suggesting that A was the original and both O and
B are mutations of this. It also suggests that there are many
more differences than those I cited previuosly.

More differences requires more time ??

I also, in the context of a previous question found this interesting::

"When we consider the direction of
substitutions, it is clear that there is a bias toward AT richness; G-to-A and C-to-T changes are much more abundant than A-to-G and T-to-C changes."

If some substitutions are more likely than others (for some
unknown but deterministic reason) doesn't that make parallel
evolution more likely. If we all start from the same place
and there are some 'rules' governing substitution then we
could all end up in a similar place.


This message is a reply to:
 Message 9 by Tranquility Base, posted 07-23-2002 9:10 PM Tranquility Base has responded

Replies to this message:
 Message 11 by Tranquility Base, posted 07-28-2002 11:15 PM Peter has responded

  
Tranquility Base
Inactive Member


Message 11 of 14 (14347)
07-28-2002 11:15 PM
Reply to: Message 10 by Peter
07-25-2002 4:30 AM


Peter

Since (from the source you or someone posted) we discovered that O 'produces no antigen' then that would be the reason to suspect that O is due to a deletion. A single insertion wont make an active gene from random DNA. DNA coding for a functional and folded protein far more easily will yieled non-functional alleles by deletions. I'm not trying to argue as a creaitonist here - this is standard Mol/Struc Biol.

The key point is that A and B are probably active functioning enzymes or something. Life is not ust a series of letters - the genes code for functioning enzymes and structural proteins. I'm not trying to kid anyone here.

I would love to know the details of waht protien A and B code for.

So OO is type O blood (like me) so it can't be overly important (if our fact that O is inactive is true)!

I agre dominant/recessive model is a simplification but in some cases it will be a warranted one.

In principle deterministic mutaitonl baises would make parallel evolution more likely - I agree. But it is truly imposible to imagine a scenario where this could take us from random DNA to DNA that codes for folded proteins that have just the right functions! I can imagine a functional gene in chimps and man mutating to the same thing due to either (i) a codon bias or (ii) something that is tolerated (or even advantagesou) in both species.

I look forward to finding time to read your web links.

[This message has been edited by Tranquility Base, 07-28-2002]


This message is a reply to:
 Message 10 by Peter, posted 07-25-2002 4:30 AM Peter has responded

Replies to this message:
 Message 12 by Peter, posted 07-29-2002 3:41 AM Tranquility Base has responded

  
Peter
Member (Idle past 35 days)
Posts: 2161
From: Cambridgeshire, UK.
Joined: 02-05-2002


Message 12 of 14 (14367)
07-29-2002 3:41 AM
Reply to: Message 11 by Tranquility Base
07-28-2002 11:15 PM


quote:
Originally posted by Tranquility Base:
Peter
Since (from the source you or someone posted) we discovered that O 'produces no antigen' then that would be the reason to suspect that O is due to a deletion. A single insertion wont make an active gene from random DNA. DNA coding for a functional and folded protein far more easily will yieled non-functional alleles by deletions. I'm not trying to argue as a creaitonist here - this is standard Mol/Struc Biol.

That makes sense ... I wasn't asking as an evolutionist ... just
asking in general. Some of the other references suggest that O
came from A too.

quote:
Originally posted by Tranquility Base:

The key point is that A and B are probably active functioning enzymes or something. Life is not ust a series of letters - the genes code for functioning enzymes and structural proteins. I'm not trying to kid anyone here.

I would love to know the details of waht protien A and B code for.


I think that's more or less covered in some of the links I posted.

quote:
Originally posted by Tranquility Base:

So OO is type O blood (like me) so it can't be overly important (if our fact that O is inactive is true)!

Not unless you need a tranfusion (People with type O blood
can only have type O blood, but anyone can have ours, provided
the rhesus factors are OK (I'm negative so I'm a universal donor))

quote:
Originally posted by Tranquility Base:

I agre dominant/recessive model is a simplification but in some cases it will be a warranted one.

In principle deterministic mutaitonl baises would make parallel evolution more likely - I agree. But it is truly imposible to imagine a scenario where this could take us from random DNA to DNA that codes for folded proteins that have just the right functions! I can imagine a functional gene in chimps and man mutating to the same thing due to either (i) a codon bias or (ii) something that is tolerated (or even advantagesou) in both species.


Only sequences that produce working proteins (whatever they
work for) would 'survive' though in a ToE sense. Once there
us a simplistic organism (maybe one of those RNA jobbies) producing
working proteins, they would multiply, and the evo process gets
a foothold.

In our timescale we have about a billion years to develop the first
working protein set after all. (Is that an american billion or
a british billion?)


This message is a reply to:
 Message 11 by Tranquility Base, posted 07-28-2002 11:15 PM Tranquility Base has responded

Replies to this message:
 Message 13 by Tranquility Base, posted 07-29-2002 4:03 AM Peter has responded

  
Tranquility Base
Inactive Member


Message 13 of 14 (14368)
07-29-2002 4:03 AM
Reply to: Message 12 by Peter
07-29-2002 3:41 AM


^ American billion (10^9). The Brit one got redefined to the American one (and they abolished milliard) I'm pretty sure. I've never heard of Brit's talking about milliard-year old universes (thankfully)!

PS - thanks for the info. The OO being universal makes sense from a folding/expression POV - if it isn't folded or expressed it wont generate an immune response whereas A or B in us will.

[This message has been edited by Tranquility Base, 07-29-2002]


This message is a reply to:
 Message 12 by Peter, posted 07-29-2002 3:41 AM Peter has responded

Replies to this message:
 Message 14 by Peter, posted 07-29-2002 5:07 AM Tranquility Base has not yet responded

  
Peter
Member (Idle past 35 days)
Posts: 2161
From: Cambridgeshire, UK.
Joined: 02-05-2002


Message 14 of 14 (14373)
07-29-2002 5:07 AM
Reply to: Message 13 by Tranquility Base
07-29-2002 4:03 AM


quote:
Originally posted by Tranquility Base:
^ American billion (10^9). The Brit one got redefined to the American one (and they abolished milliard) I'm pretty sure. I've never heard of Brit's talking about milliard-year old universes (thankfully)!

Thanks ... I've wondered that for ages


This message is a reply to:
 Message 13 by Tranquility Base, posted 07-29-2002 4:03 AM Tranquility Base has not yet responded

  
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