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Topic: Introduction to Systems Biology (Read 17060 times) previous topic - next topic

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Re: Introduction to Systems Biology
Reply #3650
Bottom line: there is a hell of a lot more genetic diversity in the human population than is represented in that outdated reference.
Yeah. The wrenches have been beat up. They aren't new any more.
See, here's where your moronic analogies serve only to reinforce your militant ignorance.
"old" or "new", shiny or "beat up" has nothing to do with it.
There are    > 2000   known alleles for a the peptidase A gene*.
You asserted that it was a "hard cold fact" that there was just one.
Almost all of those alleles are fully functional.
Nothing "beat up" about them.

* and this is just one randomly selected example.
Great. Let's compare the sequences, shall we?
"We" already did.

What's your point?
Okay you say that there are 2,000? And Cavalli Sforza just used 31? I can't remember the exact number.  Here's my prediction. I predict that 19971999 of these will be very minor variations of the 31 in Cavalli Sforza's list.  And if I am correct that there are three in his list, then I predict that there will be a wide sequence Divergence between at least two of them. Possibly a wide Divergence between all three.
So now we argue about what "very minor" means.

  • RAFH
  • Have a life, already.
Re: Introduction to Systems Biology
Reply #3651
To take one example:
in that Table 1.3.1, Cavalli-Sforza lists    1    allele for Peptidase A.

NCBI lists 2128 DNA variants of that gene.

It's probable that, in 1994 (actually, probably much earlier, as the 1994 book was reviewing published literature) the only recognized allelic differences were those detectable by a physical difference - like electrophoretic mobility - of the protein.
Yes. As In, differences that actually make a difference in the phenotype and that exceed some minimum threshold of sequence difference.

It seems that I'm going to have to back up even further and do a lesson on the difference between a brand new crescent wrench and a brand new  pipe wrench and include info about why adding an old beat-up pipe wrench and an old beat-up crescent wrench does not add diversity to the group.

At least not in the sense that matters for what I'm talking about.
And you are back to mutation / error means damage, which has negative connotations.  You know it's not true.  Therefore, you are again being DISHONEST.
Again?

I would suggest "Still" would be a more appropriate term.
Are we there yet?

  • RAFH
  • Have a life, already.
Re: Introduction to Systems Biology
Reply #3652
Because I can already see that we're going to have to spend a lot of time on this topic.
And yet, the more you post, the more people are convinced you don't understand any of it.
Seems sort of pointless.

Unless you are preaching to a silent choir behind the curtain.

The silence is because there's nobody there.
Are we there yet?

  • RAFH
  • Have a life, already.
Re: Introduction to Systems Biology
Reply #3653
Dave, many people find the adage

 Better to remain silent and be thought a fool than to speak and to remove all doubt.

to be helpful.  Unfortunately, with your latest foray into genetics, you have opened your mouth, and removed all doubt, that you are, in fact, a fool.  Deal with it.  You don't know what you are talking about.  And are absolutely in no position to be teaching anyone here.
I dunno, Bluffy could well be a sterling example of bad genetic errors.
Are we there yet?

Re: Introduction to Systems Biology
Reply #3654
Bottom line: there is a hell of a lot more genetic diversity in the human population than is represented in that outdated reference.
Yeah. The wrenches have been beat up. They aren't new any more.
See, here's where your moronic analogies serve only to reinforce your militant ignorance.
"old" or "new", shiny or "beat up" has nothing to do with it.
There are    > 2000   known alleles for a the peptidase A gene*.
You asserted that it was a "hard cold fact" that there was just one.
Almost all of those alleles are fully functional.
Nothing "beat up" about them.

* and this is just one randomly selected example.
Great. Let's compare the sequences, shall we?
"We" already did.

What's your point?
Okay you say that there are 2,000? And Cavalli Sforza just used 31? I can't remember the exact number.  Here's my prediction. I predict that 19971999 of these will be very minor variations of the 31 in Cavalli Sforza's list.  And if I am correct that there are three in his list, then I predict that there will be a wide sequence Divergence between at least two of them. Possibly a wide Divergence between all three.
So now we argue about what "very minor" means.
while still ignoring the fact that Dave has no clue what it means wrt evolution to say that a population is diverse or that a mutation can only be judged as vsdm or vsbm in the context of its environment.
Love is like a magic penny
 if you hold it tight you won't have any
if you give it away you'll have so many
they'll be rolling all over the floor

Re: Introduction to Systems Biology
Reply #3655
Bottom line: there is a hell of a lot more genetic diversity in the human population than is represented in that outdated reference.
Yeah. The wrenches have been beat up. They aren't new any more.
See, here's where your moronic analogies serve only to reinforce your militant ignorance.
"old" or "new", shiny or "beat up" has nothing to do with it.
There are    > 2000   known alleles for a the peptidase A gene*.
You asserted that it was a "hard cold fact" that there was just one.
Almost all of those alleles are fully functional.
Nothing "beat up" about them.

* and this is just one randomly selected example.
Great. Let's compare the sequences, shall we?
"We" already did.

What's your point?
Okay you say that there are 2,000? And Cavalli Sforza just used 31? I can't remember the exact number.  Here's my prediction. I predict that 19971999 of these will be very minor variations of the 31 in Cavalli Sforza's list.  And if I am correct that there are three in his list, then I predict that there will be a wide sequence Divergence between at least two of them. Possibly a wide Divergence between all three.
So now we argue about what "very minor" means.
Hm, "facilitates the proliferation of colon cancer" and "poor prognosis in resected pancreatic cancer"
don't sound very minor.
  • Last Edit: March 21, 2018, 01:10:37 PM by Saunt Taunga

Re: Introduction to Systems Biology
Reply #3656
Because I can already see that we're going to have to spend a lot of time on this topic.
And yet, the more you post, the more people are convinced you don't understand any of it.
Seems sort of pointless.

Unless you are preaching to a silent choir behind the curtain.

The silence is because there's nobody there.
Soctratic vibes.

  • RAFH
  • Have a life, already.
Re: Introduction to Systems Biology
Reply #3657
Bottom line: there is a hell of a lot more genetic diversity in the human population than is represented in that outdated reference.
Yeah. The wrenches have been beat up. They aren't new any more.
See, here's where your moronic analogies serve only to reinforce your militant ignorance.
"old" or "new", shiny or "beat up" has nothing to do with it.
There are    > 2000   known alleles for a the peptidase A gene.
You asserted that it was a "hard cold fact" that there was just one.
Almost all of those alleles are fully functional.
Nothing "beat up" about them.
2000 ways to "damage" something, yet almost all are fully functional?  Oh no, there goes Dave's unwarranted assumptions!

My bet is that he still, even after been shown things like this, will not learn, and will come back with repetitions of his misunderstandings as though nothing was refuted.   This is not a risky prediction, at all.
There's a reason Bluffy insists mainstream life sciences (and others as relevant) make unwarranted assumptions, it's just more of his projection. He does it, so he assumes (unwarrantedly) everyone else does.
Are we there yet?

  • Pingu
Re: Introduction to Systems Biology
Reply #3658
I really want to know what Dave means by "very minor". 

I mean there are plenty of quite strong associations in GWA studies that are single nucleotide substitutions.  Are they "very minor"?
I have a Darwin-debased mind.

  • Pingu
Re: Introduction to Systems Biology
Reply #3659
And actually, of course genetic diversity with "very minor" phenotypic effects are EXACTLY what a population needs in order to adapt.

A slightly longer neck here, a slightly deeper beak there.
I have a Darwin-debased mind.

  • VoxRat
  • wtactualf
Re: Introduction to Systems Biology
Reply #3660
I really want to know what Dave means by "very minor". 

I mean there are plenty of quite strong associations in GWA studies that are single nucleotide substitutions.  Are they "very minor"?


Single base pair substitutions make the difference between A, B and O alleles in the ABO blood group gene.
"Very minor" in terms of genetic difference, but fairly major in terms of phenotypic consequences.
"I understand Donald Trump better than many people because I really am a lot like him." - Dave Hawkins

Re: Introduction to Systems Biology
Reply #3661
Dave, how do you determine if a mutation (of any sort) is slightly deleterious or slightly beneficial?
Love is like a magic penny
 if you hold it tight you won't have any
if you give it away you'll have so many
they'll be rolling all over the floor

Re: Introduction to Systems Biology
Reply #3662
I really want to know what Dave means by "very minor". 

I mean there are plenty of quite strong associations in GWA studies that are single nucleotide substitutions.  Are they "very minor"?


Single base pair substitutions make the difference between A, B and O alleles in the ABO blood group gene.
"Very minor" in terms of genetic difference, but fairly major in terms of phenotypic consequences.

Yeah, Dave seems to think that A, B, and O alleles very different in terms of sequence and therefore all of the 2000 SNPs will cluster into "A+RM", "B+RM" and "O+RM", proving that A, B and O are the original alleles that Noah carried. 

ETA: Noah AND his wife...   Long day of science-ing...
  • Last Edit: March 21, 2018, 01:51:50 PM by entropy
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins

  • Pingu
Re: Introduction to Systems Biology
Reply #3663
I really want to know what Dave means by "very minor". 

I mean there are plenty of quite strong associations in GWA studies that are single nucleotide substitutions.  Are they "very minor"?


Single base pair substitutions make the difference between A, B and O alleles in the ABO blood group gene.
"Very minor" in terms of genetic difference, but fairly major in terms of phenotypic consequences.


And, conversely, can be usefully subtle.  Val-Met alleles are often important, and sometimes one is helpful and sometimes the other, and sometimes which one is helpful depends on which of allele of some other gene is present. At least that's what the evidence seems to be showing in my field.  Things that we know are highly heritable turn out to be associated with lots of tiny variants each of very small effect.
I have a Darwin-debased mind.

  • VoxRat
  • wtactualf
Re: Introduction to Systems Biology
Reply #3664
Yeah, Dave seems to think that A, B, and O alleles very different in terms of sequence and therefore all of the 2000 SNPs will cluster into "A+RM", "B+RM" and "O+RM", proving that A, B and O are the original alleles that Noah carried. 
  :sadyes:

Though the > 2000 SNPs I mentioned were for peptidase A.
I find only ( heh! ) 827 for the human ABO gene.
"I understand Donald Trump better than many people because I really am a lot like him." - Dave Hawkins

Re: Introduction to Systems Biology
Reply #3665
Yeah, Dave seems to think that A, B, and O alleles very different in terms of sequence and therefore all of the 2000 SNPs will cluster into "A+RM", "B+RM" and "O+RM", proving that A, B and O are the original alleles that Noah carried. 
  :sadyes:

Though the > 2000 SNPs I mentioned were for peptidase A.
I find only ( heh! ) 827 for the human ABO gene.
Yeah, I assume because he started talking about three alleles that he got confused and went back to A, B, O.  Or at least forgot that there was only one peptidase A alleles in his table.
  • Last Edit: March 21, 2018, 01:50:50 PM by entropy
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins

Re: Introduction to Systems Biology
Reply #3666
I will even make a risky prediction.
Will anybody agree it is risky?
Or a prediction?
Or that success or failure can be distinguished?
So, so far, Pingu seems to disagree with "risky".
The other two are undecided pending clarification of "very minor".

Re: Introduction to Systems Biology
Reply #3667
I will even make a risky prediction.
Will anybody agree it is risky?
Or a prediction?
Or that success or failure can be distinguished?
So, so far, Pingu seems to disagree with "risky".
The other two are undecided pending clarification of "very minor".
If I'm correct that he's getting at there being "original alleles" that are very divergent from eachother, then clusters of "degenerated alleles" descended from those to account for all the other SNPs, then his prediction is not even wrong.
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins

Re: Introduction to Systems Biology
Reply #3668
Yeah, Dave seems to think that A, B, and O alleles very different in terms of sequence and therefore all of the 2000 SNPs will cluster into "A+RM", "B+RM" and "O+RM", proving that A, B and O are the original alleles that Noah carried. 
  :sadyes:

Though the > 2000 SNPs I mentioned were for peptidase A.
I find only ( heh! ) 827 for the human ABO gene.
Yeah, I assume because he started talking about three alleles that he got confused and went back to A, B, O.  Or at least forgot that there was only one peptidase A alleles in his table.
OK busy day.  Yeah I couldn't remember how many alleles CS listed in his table for peptidase.  If there's only one common allele, then it would be hard to guess if it's an original "ark allele" or not.  There are others that have more common alleles like the ABO gene mentioned above.  This paper has this to say about ABO ...
Quote
The A101 allele is usually used
as the reference against which all other alleles are
compared although the cDNA sequence of the
A102 allele was reported first (Yamamoto et al.
1990b).
The O101 allele differs from the A101 allele by
a single base (G) deletion at nucleotide (nt) 261
corresponding to amino acid 87 of the A
transferase (Fig. 3; Yamamoto et al. 1990a). This
shifts the reading frame of the coding sequence
and generates a premature termination codon
downstream from the deletion. It is predicted to
produce an altered and shortened polypeptide of
116 amino acids that lacks the C-terminal
catalytic domain and hence is enzymatically
inactive.
The B101 allele, on the other hand, differs from
the A101 allele by seven single base substitutions
within the coding sequence at nt 297, 526, 657,
703, 796, 803 and 930 (Fig. 2; Yamamoto et al.
1990a). Four of these base substitutions (nt 526,
703, 796 and 803) result in amino acid substitutions
(residues 176, 235, 266 and 268).
https://onlinelibrary.wiley.com/doi/pdf/10.1017/S0003480001008995

So A and O are almost identical and B is a more distant "relative" of both.

I don't know enough to conclude anything but I can make this general statement ...

If Mr. and Mrs. Noah had 4 alleles per locus between them (say 20,000 loci), that's a heckuva a lot more diversity than only 2 alleles per locus X 20,000 or 2 X 15,000 + 1 X 5000 etc. and more than the minimum which would be 1 allele X 20,000 loci. 

THAT'S what I'm talking about when I'm talking about genetic diversity.

Now of course it's true that ANY difference - even a single base substitution - creates diversity ... but much of these are mistakes - copying errors ... and most of these are not beneficial (not me talking, population geneticists talking).

Re: Introduction to Systems Biology
Reply #3669
So I could invent a new index ... call it "The Hawkins Genetic Diversity Index" ...

4 x 20,000 = 80,000 is the maximum. 

1 x 20,000 = 20,000 is the minimum. 

Re: Introduction to Systems Biology
Reply #3670
Yeah, Dave seems to think that A, B, and O alleles very different in terms of sequence and therefore all of the 2000 SNPs will cluster into "A+RM", "B+RM" and "O+RM", proving that A, B and O are the original alleles that Noah carried. 
  :sadyes:

Though the > 2000 SNPs I mentioned were for peptidase A.
I find only ( heh! ) 827 for the human ABO gene.
Yeah, I assume because he started talking about three alleles that he got confused and went back to A, B, O.  Or at least forgot that there was only one peptidase A alleles in his table.
OK busy day.  Yeah I couldn't remember how many alleles CS listed in his table for peptidase.  If there's only one common allele, then it would be hard to guess if it's an original "ark allele" or not.  There are others that have more common alleles like the ABO gene mentioned above.  This paper has this to say about ABO ...
Quote
The A101 allele is usually used
as the reference against which all other alleles are
compared although the cDNA sequence of the
A102 allele was reported first (Yamamoto et al.
1990b).
The O101 allele differs from the A101 allele by
a single base (G) deletion at nucleotide (nt) 261
corresponding to amino acid 87 of the A
transferase (Fig. 3; Yamamoto et al. 1990a). This
shifts the reading frame of the coding sequence
and generates a premature termination codon
downstream from the deletion. It is predicted to
produce an altered and shortened polypeptide of
116 amino acids that lacks the C-terminal
catalytic domain and hence is enzymatically
inactive.
The B101 allele, on the other hand, differs from
the A101 allele by seven single base substitutions
within the coding sequence at nt 297, 526, 657,
703, 796, 803 and 930 (Fig. 2; Yamamoto et al.
1990a). Four of these base substitutions (nt 526,
703, 796 and 803) result in amino acid substitutions
(residues 176, 235, 266 and 268).
https://onlinelibrary.wiley.com/doi/pdf/10.1017/S0003480001008995

So A and O are almost identical and B is a more distant "relative" of both.

I don't know enough to conclude anything but I can make this general statement ...

If Mr. and Mrs. Noah had 4 alleles per locus between them (say 20,000 loci), that's a heckuva a lot more diversity than only 2 alleles per locus X 20,000 or 2 X 15,000 + 1 X 5000 etc. and more than the minimum which would be 1 allele X 20,000 loci. 

THAT'S what I'm talking about when I'm talking about genetic diversity.

Now of course it's true that ANY difference - even a single base substitution - creates diversity ... but much of these are mistakes - copying errors ... and most of these are not beneficial (not me talking, population geneticists talking).
::)
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins

Re: Introduction to Systems Biology
Reply #3671
So I could invent a new index ... call it "The Hawkins Genetic Diversity Index" ...

4 x 20,000 = 80,000 is the maximum. 

1 x 20,000 = 20,000 is the minimum. 
::)^ ::)
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins

Re: Introduction to Systems Biology
Reply #3672
...
THAT'S what I'm talking about when I'm talking about genetic diversity.
Bullshit.  Up until this point you've been talking about diversity with respect to the genome composition of single haploid bacterial cell.  Nice to see you're finally walking back from that fuck up though.
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins

Re: Introduction to Systems Biology
Reply #3673
...
THAT'S what I'm talking about when I'm talking about genetic diversity.
Bullshit.  Up until this point you've been talking about diversity with respect to the genome composition of single haploid bacterial cell.  Nice to see you're finally walking back from that fuck up though.
Oh sorry. I meant to write "THAT'S what I'm talking about when I'm talking about genetic diversity IN HUMANS"

We'll talk about bacterial later.

Re: Introduction to Systems Biology
Reply #3674
...
THAT'S what I'm talking about when I'm talking about genetic diversity.
Bullshit.  Up until this point you've been talking about diversity with respect to the genome composition of single haploid bacterial cell.  Nice to see you're finally walking back from that fuck up though.
Oh sorry. I meant to write "THAT'S what I'm talking about when I'm talking about genetic diversity IN HUMANS"

We'll talk about bacterial later.
::)
While you were getting your PhD in virology, I got my PhD in truth detection. :wave:  Dave Hawkins