Researchers: Thousands of genes influence disease

I'm going to start calling software bugs "code variants." I wonder how that will fly. Phinehas

I look forward to any evidence that this is the case. wd400

Allele means anything you "need" it to mean. PaV

What's flexible about it? Allele means genetic variant. There are more precise terms if you want to talk about single nucleotide variants, insertion-deletion variants, copy number variants etc. But I don't think there is anything flexible about the way allele is used. wd400

wd400: It is your completely flexible notion of allele that drives me mad. You can't do science they way your profession has decided to do it. PaV

wd400 @14: Thanks. So it sounds like you would say that in case #1, it would be appropriate to say that we have identified the gene for the particular disease. (It would probably be better to say that we have identified the mutation that caused the particular disease, but OK.) As far as #3, given that the penetrance of an allele can vary, what is the upshot of that observation? Logically, it means there are other things going on, potentially lots of things. I agree that we can call such an allele a risk factor. We can even say we have identified a gene "associated with" a disease, as long as we are clear what that means (in most cases it is a statistical measure, not based on our understanding of what such an allele is actually doing or causing in within the cell's biochemistry). But to say that the associated gene is the gene for the disease strains both language and the facts. What about #2? Which lab, if any, gets to announce that they have discovered the gene for the disease? -----

If an allele of unknown molecular function (almost) always produces a given trait then it’s fair to call it the gene for that trait.

In the context of functional, but different, traits (hair color, wing coloration, etc.), I agree. However, I would just note that this approach would be very strained in the context of disease or broken function. If I have heart disease, is it fair to say I have the gene for the trait of heart disease? That is a very strained way of looking at the underlying biological reality and a highly unusual way of describing the engineering reality. After all, we can't just say that the absence of proper function means I have the "trait" for absence of proper function. That makes the concept of a trait meaningless. After all, I also have the "trait" of the absence of wings and flight. Which gene to I have that causes me to have the trait for non-flight? When we get past the terminology and the statistics and the guesswork, and start looking at the underlying engineering reality, this is the situation: We don't have genes for non-function. We have genes for function, which sometimes get broken. When we are dealing with functional, but different, traits (hair color, wing coloration, etc.), then it makes sense to talk about genes for a particular trait. No problem. I'm on board with that. However, in the context of disease, broken genes, and non-function, it doesn't make nearly as much sense. Eric Anderson

Again with this madness. In the peppered moth case there are two alleles, they differ because one of them has transposon insertion which the other lacks. Neither allele makes a different protein isoform, but that is not part of the definition of "allele" (whatever the intro to one Wikipedia article says), so there is not twisting to call the variant version of this gene gene-variants. wd400

wd400:

Allele has a specific definition, a genetic variant.Allele has a specific definition, a genetic variant.

What's your specific definition of a "gene"? Wikipedia: "Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits." But, if, as in the "peppered moth," a change occurs in an 'intron,' which does not affect the protein produced by the gene, you have said, IIRC, that that is part of the "allele." But there is no variation in the protein, which means that there is no variation in the gene, which means the allele hasn't changed; hence, the "allele" hasn't changed. But, of course, it must have changed according to neo-Darwinism. Therefore, an "allele" is much more than a "gene variant." And, in effect, it becomes whatever it needs to become to maintain orthodoxy. QED My point is made. I don't care to discuss it further. PaV

PaV, You appear to have lost the plot. Allele has a specific definition, a genetic variant. I'm not sure what the rest of your rant has to do with anything. It is difficult to assign populations to species, but we have a pretty good definition (at least for plants and animals): a population-lineage that maintains a distinct evolutionary trajectory. Under that definition species can interbreed from time to time (and indeed many do), as long as recombination doesn't drag the two species together (i.e. hybrids must be rare or hybrid genotypes must be selected against). If ID has a better framework in which to understand species I'd love to hear it. EA, You're three exaples differ both in the molecular understanding of the allele's phenotype and the penetrance of the allele. Only the latter is relevant to saying an allele is causative. If an allele of unknown molecular function (almost) always produces a given trait then it's fair to call it the gene for that trait. On the other hand, if an allele with a deeply understood molecular phenotype has low penetrance then it is better to call it a "risk allele" (as is common practice in genetics). wd400

wd400, I'm sorry that you are dismissive of the point I have described, particularly after I was able to provide several examples with an easy Google search in response to your claim that I had no examples. Again, my point has nothing to do with whether we can use a word like "allele" to describe a broken gene. My point relates to the theoretical gloss that attends the description of the underlying biology. (If anything, the insistence on using the single word "allele" to describe both a functional gene and a broken gene underscores my point.) Let me try one more time, in question format. We have the following real-world cases: 1. We know that a particular broken gene X, acting alone, is the exclusive reason why a specific biological function is not working. This has been worked out by experiment and by biological principles. We know what the altered nucleotide does, how it impacts the resulting protein, and why the protein no longer performs its proper function. In this case the altered nucleotide has a clear effect and produces the same result every time. 2. A know that a particular broken gene X, acting within a complex of genes X-Y-Z rather than alone, results in failed biological function. Lab A has done careful and detailed studies on gene X and knows exactly how the altered nucleotide impacts the resulting protein and why the protein no longer performs its proper function. Lab B has also done careful and detailed studies and knows exactly how an altered nucleotide in broken gene Y impacts the resulting protein and why the protein no longer performs its proper function. Lab C reports a similar result for gene Z. 3. We infer that a particular gene is associated with a disease, based on genetic mapping and disease comparisons (either clinical studies or surveys). In these cases there is typically a risk factor associated with the gene, which can sometimes vary across a wide range. People with the associated gene have an increased risk, but a particular individual may or may not get the disease. In these cases it is also quite common that we don't actually know whether the associated gene is even directly involved in the disease. ----- In which of these cases do you think it would be appropriate for a researcher to claim that they have identified the gene for the relevant disease? It is worth noting that #2 and #3 are probably more common than #1. Eric Anderson

wd400: As expected, you've described nothing: "It doesn't look like anything, because you can't see it." As expected, your "allele" is just about anything you want it to be. So, Darwinism is about "changing allele frequencies." This means anything you want it to mean. This allows you--at least in your mind--to accomodate your "theory" to anything that happens. IOW, it predicts "nothing," and explains "everything." How worthless a concept. Next, you can explain to us what a "species" is. Oops, that's another hard one, right? Species are populations that don't interbreed--like Darwin's finches. That is, until it's found out that they do, in fact, interbreed and form hybrids. So, no working definition of an 'allele', and no working definition of 'species'. How wonderful. PaV

An allele is a gene variant. It doesn't look like anything, because you can't see it. A particular copy of an allele is made of DNA. Different alleles are of different lengths. I'm sure a highschool biology text could help you understand different types of genetic variation. wd400

wd400: Please explain to all of us EXACTLY what an 'allele' is: What does it look like? Where do we find it in the cell? Is it all DNA? How long is it? Where does it begin? Where does it end? PaV

This just meaninglessness piled upon meaningless. I have not claimed now uses the phrase "gene for", I have made the point many alleles really are causative of particular traits. That's true regardless of paradigm, this strange narrative that you say drives biologists to make mistakes about the underlying reality of the world (although you have still failed to point out any mistake). wd400

Of course they are talking about an allele. And what is an allele in this case? A broken gene that, if not broken, would contribute to larger overall function within whatever cellular machinery it exists. Under the Darwinian paradigm a proper-functioning allele and a broken-gene allele are just two peas in a pod -- all part of the ongoing mutation-selection drama that supposedly underlies all of biology. Furthermore, the very insistence you keep bringing to the table with the word "allele" belies the fact that you tend to view them as just two different "alternative forms" of a gene. That is a simplistic perspective that obscures the underlying reality, rather than enlightening. In the present context of disease discussion, one is a functional sequence that operates within the context of a larger purposeful arrangement. The other is broken. In no other field would any rational person come up with fancy terminology to obscure the underlying reality. One can't imagine a computer programmer offering up to his boss some corrupted code and then claiming it is just an alternative form of the good code -- just another "version." It isn't. One is designed and is working properly. The other is a degenerate form of the designed version.

Instead, you create this strange narrative to oppose, without actually pointing to an example of it existing.

What are you talking about? The first quoted paragraph in the OP is an example. 15 seconds on Google netted me biological papers with titles like "New disease gene for axon degeneration" and "A gene for Stargardt's disease" and even a paper that analyzed patient perceptions of the phrasing of genetic risk factors, including the phrase "a gene for heart disease." Examples abound. It is unfortunate that your indignant "we biologists know what we are talking about and we can't be questioned" attitude leads you to be completely blind to these kinds of nuances. Eric Anderson

There is no "nuance" to what you are saying. There is just nothing at all to it.

And yet . . . you still keep referring to it as “causative”. And we are regularly treated to news stories and press releases from researchers about a broken gene being the gene “for” a particular disease. I’m not sure why you can’t see where the narrative comes from. It comes from the perverted Darwinian view of biology, as I have clearly explained, and as you yourself keep demonstrating. Don’t complain about me making up this narrative. I’m the one trying to challenge it.

Again, when a researcher says gene for (or contributing to) a trait they mean gene the sense of allele. Your bloviation doesn't provide any explanation as to why this is wrong. Instead, you create this strange narrative to oppose, without actually pointing to an example of it existing. wd400

I'm sorry you were unable to understand the nuance. As I mentioned, such nuances will probably be lost on Darwinists, who view all of biology through an opaque bottom-up mutation-builds-biology lens.

I have no idea where this narrative about broken genes being seen as another function comes from . . .

And yet . . . you still keep referring to it as "causative". And we are regularly treated to news stories and press releases from researchers about a broken gene being the gene "for" a particular disease. I'm not sure why you can't see where the narrative comes from. It comes from the perverted Darwinian view of biology, as I have clearly explained, and as you yourself keep demonstrating. Don't complain about me making up this narrative. I'm the one trying to challenge it. Eric Anderson

This is a really long-winded way to say nothing. I'm really not sure you know what allele means, and I have no idea where this narrative about broken genes being seen as another function comes from (other than your own misunderstanding of biology). That gene products interact with each other and mutants an individual genes might effect multiple traits is part of high school biology in most of the world (though perhaps not the US). It remains the fact an allele for a simple Mendelian trait is causative. If you this allele instead of the wildtype you will have the trait. Even for more complex traits alleles contribute risk or, for quantitative traits, an effect. wd400

wd400: You are missing the nuance. I am not attempting to require a broad change in how biological bench science should be done. I am simply noting an unhealthy evolutionary mindset that seems to pervade biological descriptions. Sure, biologists, when pressed, will acknowledge that genes are part of a broader system and that everything has to be in place for function. Sure, biologists, when pressed, may admit that natural selection isn't actually a creative force in nature. But in both of these cases they are constantly slipping back into terminology and attitude that contradicts this acknowledgement. In other words, they might know better, but the theory keeps dragging them down the wrong road. Even you, right after indignantly noting that everyone knows better, turned right around and said that there is a gene for a disease -- whether we use the fancy word "allele" or not. Yes, since we are dealing with language we have some ability to define terms. Yes, we could use sloppy terminology and redefine a broken gene as a gene for a negative outcome. And this makes sense to some extent under the Darwinian paradigm. After all, in the Darwinian paradigm chance changes, mutations, mistakes -- all are part of the bottom-up creative process that supposedly built all of biology. And so from the Darwinian perspective, a broken gene is just as much a part of the creative process as a good gene. Neither is inherently more purposeful or more intentional or more meaningful than the other. As you intimated, the functional gene and the broken gene are just two different peas (alleles) in the pod. This twisted view of biological origins and biological systems then leads to strained terminology and strange approaches to the evidence. In contrast, if one acknowledges a biological system as a top-down, functionally-integrated, purposeful arrangement, then we see a broken gene for what it is: a broken gene, not as just another example of the amazing Darwinian creative process that happens to be heading in a different direction. We see it properly as a break down, as leading away from function. No mechanic when servicing a non-functioning engine would, upon finding a snapped piston rod, proclaim that he had discovered the "part for a broken engine." The attitude and nuance comes in the fact that the Darwinist sees all these changes and alleles as just another example of the evolutionary process. For the Darwinist it isn't that the engine was purposely assembled at the outset and then something broke. The Darwinist views the whole affair as a series of accidents, mistakes, coincidences, leading nowhere in particular. The organism is "plastic," as Darwin, described -- shifting, changing, altering, moving from one type to another. For the Darwinist the broken gene is just another function, a temporary pit stop on the way to yet another function: In the past we had the gene for a particular function, today it is a gene for a disease, some distant day in the future it will turn into a gene for some third function . . . Thus we end up with strange terminology and a twisted perspective on biological systems that belies an underlying philosophical bent regarding the unpurposeful and happenstance origin of the systems being analyzed. ----- Let me close by saying that this is a nuance regarding terminology and attitude. I fully expect that many Darwinian scientists will be able to carry on discovering broken genes quite nicely and that these discoveries will be helpful. But it will be due to reverse engineering and analysis. The Darwinian narrative won't be helpful in the bench science or the reverse engineering, and instead is just added after the fact (usually implicitly, sometimes explicitly) as an unhelpful and distracting philosophical gloss. Eric Anderson

wd400: Do you actually think biologists are not aware of this? Every “gene for” a disease is obviously also a gene for normal function.

wd400, I do not think that you address Eric Anderson's point. His point, as I understand it, is that the gene should not be viewed in isolation, but instead as a part of an intricate system involving many parts working in perfect concert which produces biological function. Not the kind of system where random mutations can do much good. Origenes

This distinction between the common perception of genes for diseases, and the more accurate view of broken genes failing to properly contribute to higher function is nuanced. But it is an important distinction, borne of a better understanding of biology, and one that helps prevent us from going down the wrong path in our research assumptions.

Do you actually think biologists are not aware of this? Every "gene for" a disease is obviously also a gene for normal function. When a geneticist is talking about a gene for a trait they are talking about an allele, in which case it really is causative (or for traits that are not simple Mendelian ones contributive). wd400

A core assumption in the study of disease-causing genes has been that they are clustered in molecular pathways directly connected to the disease.

Part of the problem is this mindset from the very outset. We regularly hear about genes that cause this or that disease or this or that biological problem. If we have that misunderstanding, then we can easily get caught in the subsequent mistake of thinking that "disease-causing genes" cluster in pathways "connected to the disease." This is an example of how the Darwinian bottom-up, stuff-happens, random-variation-builds-things, failed paradigm leads people to view things in the wrong light. In contrast, when we look at biological systems from a top-down, designed perspective -- like an engineer -- we realize that genes aren't made to cause disease. Rather, we realize that in order to get a biological function there are a thousand things that have to work in perfect concert, and that if any one of them goes wrong the system might not function. So, yes, a broken or degraded gene can prevent the system from functioning properly, but it is not as though we have discovered "the gene" for a particular disease. It would be like a child examining a supercomputer and discovering that the cable from the graphics port is cut and then proclaiming that he had discovered which computer part causes the monitor to not work. This distinction between the common perception of genes for diseases, and the more accurate view of broken genes failing to properly contribute to higher function is nuanced. But it is an important distinction, borne of a better understanding of biology, and one that helps prevent us from going down the wrong path in our research assumptions. Eric Anderson