Sharing An Experience...

[unknown]

I was sitting at my desk, minding my own business and I hear the guys across the room start talking. I usually try to ignore them, because their conversations usually include stuff about how their girlfriends are mad at them or how they plan on working out...blah, blah. But, I hear one of them say that there are all these people in the world with autoimmune diseases and that science is the only thing keeping these people alive because they would have just died out a long time ago and that it's all about Darwin.

When I heard this, I wanted to get up and start yelling at him. I can't believe that a person would say such a horrible thing and honestly, I think he's wrong. Almost everyone in my family has an autoimmune disease, but they've all lived long lives so far (except for my mother who died in her 30's of CNS type lupus). I mean, us celiacs (without science to diagnosis us), it would be a sucky, painful life, but we'd still live and be able to procreate, right? Am I wrong?

I mean, who knows...I just can't believe he'd say that, and I want him to be wrong. I want to say something, but I won't. I haven't even told all my co-workers about my celiac disease and I don't want to for sure now that I know how some people view this sort of thing. I can't help but think about this. He's wrong, right? I mean, heart disease is the number 1 killer I thought. I guess I'm just trying to find a good argument for myself to feel better. I almost feel like I shouldn't exist, but I know I shouldn't let someone else's words affect me.

[kareng]

To some extent they are correct. Does the guy wear glasses or contacts? 2500 (or whatever )years ago, a guy with bad eyesight would have been eaten or fallen off a cliff. He wouldn't procreate to make babies with bad eye sight.

Really, without modern medicine, many of us would have died. My breech baby and I would have died. People with forms of heart disease would die without the medicine or a procedure. Whole families were wiped out by the flu in the States when my grandma was young. Might be that side of the families' over re-active immune system saved her. Who knows?

They don't know much about what they are talking about. I wouldn't worry about it. Without science, he might have dies of a childhood disease.

[tictax707]

Darwin? DAWRIN? If you want to talk "dawrin" those guys would be offed via low intellegence alone. Did they get shots as a kid? Who is to say how they would have fared? I heard once in a talk given at a university that the gene for celiac disease may survived because it conferred an evolutionary advantage by protecting from bacterial infection. Go tell them THAT.

My source is from right here at "home"

https://www.celiac.com/articles/22163/1/Evolutionary-and-Functional-Analysis-of-Celiac-Risk-Loci-Reveals-SH2B3-as-a-Protective-Factor-against-Bacterial-Infection/Page1.html

Nothing irks me as a scientist than people running around quoting science who don't understand it, or take the time to understand it.

[unknown]

Yeah, I guess he is right, but why is he only focusing on autoimmune diseases? That's what's really bothering me. I would be dead now, too. I've had pneumonia 3 times and that first time would have took me out. So yeah, he's right in a dumb kind of way I'll just think of it that way.

[unknown]

Darwin? DAWRIN? If you want to talk "dawrin" those guys would be offed via low intellegence alone. Did they get shots as a kid? Who is to say how they would have fared? I heard once in a talk given at a university that the gene for celiac disease may survived because it conferred an evolutionary advantage by protecting from bacterial infection. Go tell them THAT.

My source is from right here at "home"

https://www.celiac.com/articles/22163/1/Evolutionary-and-Functional-Analysis-of-Celiac-Risk-Loci-Reveals-SH2B3-as-a-Protective-Factor-against-Bacterial-Infection/Page1.html

Nothing irks me as a scientist than people running around quoting science who don't understand it, or take the time to understand it.

Hahahhaha, YES! Thank you!

[mushroom]

It is true that without science the world's population would be hugely reduced. I'm not sure what percentage the autoimmune folks would contribute since many of them don't develop their diseases until after the age that most of the early peoples used to die at. He was just blowing steam.

[saintmaybe]

As an evolutionary biologist, I'd have to say that there's probably a reason that the genes for celiac disease have been preserved in the gene pool, much like the genes for sickle cell anemia have (people with one copy have increase immunity to malaria).

Richard Dawkins (a very famous evolutionary biologist) would say that even though modern medicine has made it possible for celiacs to survive, there are other modern day pressures that make us very unhealthy.

What about war? Famine? Driving around in cars and getting into wrecks at 60 miles an hour? Guns? None of these are exclusive to any specific population, and kill off lots of people before they have kids.

Finally, I'd watch what those dudes stuff in their mouths for lunch every day. Not that celiac necessarily confers some healthy advantage, but if they're packing on a few pounds, chances are, they're already courting prediabetes, hypertension, and heart disease, very modern and very American diseases.

They're idiots who don't actually know anything about how evolution works.

Finally, assuming you're not depressed, it's adolescent to angst about whether you have a right to be here. You didn't ask to be born, no, but here you are. You have a fundamental right to a healthy, fulfilling life while you're here, whatever evolutionary theory has to say.

[unknown]

Finally, assuming you're not depressed, it's adolescent to angst about whether you have a right to be here. You didn't ask to be born, no, but here you are.

I am depressed! I was just diagnosed and even though I feel so much better now, it's still depressing. Especially when I over heard someone say what he said. It hurt my feelings and made me feel ashamed of something that I had no control over, but yes...I do have a right to be here. I need to just get over it and accept the fact that some people are just like that.

[Takala]

"Most of the world's work is done by people who aren't feeling very well."

- Winston Churchill

[Jestgar]

Yeah, I guess he is right, but why is he only focusing on autoimmune diseases? That's what's really bothering me. I would be dead now, too. I've had pneumonia 3 times and that first time would have took me out. So yeah, he's right in a dumb kind of way I'll just think of it that way.

My guess is that they say a lot of dumb things. This one just happened to have some relevance to you so you actually heard it.

[Jestgar]

As an evolutionary biologist, I'd have to say that there's probably a reason that the genes for celiac disease have been preserved in the gene pool....

As a geneticist, I disagree.

[mushroom]

As a geneticist, I disagree.

It is hard to make a case for preservation of these particular genes But then again, there are some others I have that would make an even harder case There is a little consolation in knowing that I haven't passed them on

[sariesue]

They are right many genetic diseases do shorten life span and medical science does extend the lives of some. Diseases like cystic fibrosis definately are helped by medical breakthroughs. My friend in college has CF and she went through all of the medications and treatments that she has to do every day and all of that are why she is alive. However, science does have it's limits we still have not found a cure for tay sachs. Which is a horrible condition that is a death sentence even today.

As for celiac, if left untreated it can cause problem with fertility so I don't know.

[Skylark]

As a geneticist, I disagree.

Open Original Shared Link

Open Original Shared Link

*giggles and runs away*

By the way, did your friends have their wisdom teeth out? Born by cesarean section? Ever have a strep infection in childhood that was cured with antibiotics? Manage to not die of polio becasue of vaccination? Ever have surgery? They are being cruel, but they probably had plenty of opportunities to be weeded from the gene pool themselves.

[pricklypear1971]

As one funny man said..."You can't fix stupid".

Just leave it at that and walk away.

[Jestgar]

Open Original Shared Link

Open Original Shared Link

*giggles and runs away*

*snort*

I pulled them up at work where I can get the whole article, but I won't be able to read them until later this afternoon.

[domesticactivist]

They're idiots. My dad doesn't believe in evolution but has the same kind of perspective. One thing I've learned is if someone has made an irrational belief a part of their identity there is no reasoning with it. It's also not something to take seriously or take to heart.

[Skylark]

*snort*

I pulled them up at work where I can get the whole article, but I won't be able to read them until later this afternoon.

I don't know whether the evolutionary arguments for the celiac loci are any good or not. I was teasing you, not trying to provide a reading assignment!

I do find the strong linkage disequilibrium in the HLA complex interesting. I would think haplotypes like DR3/DQ2 and DR4/DQ8 would not be under such disequilibrium if they were purely detrimental?

[domesticactivist]

Whoa, that last bit was so completely over my head! Lol

[Jestgar]

I don't know whether the evolutionary arguments for the celiac loci are any good or not. I was teasing you, not trying to provide a reading assignment!

I do find the strong linkage disequilibrium in the HLA complex interesting. I would think haplotypes like DR3/DQ2 and DR4/DQ8 would not be under such disequilibrium if they were purely detrimental?

There's a ton of stuff in high LD which could be related to some selection, or could be that chromosome just doesn't cross there.

The first paper you cited is interesting. They looked at a high ancestral coefcient to determine long haplotype stretches. rs3184504 SH2B3 was the highest with an Fst of .6 (higher than random drift) so they explored that gene further HOWEVER since they identified this with a long haploype (500kb) there are a bunch of other SNPs and genes that are dragged along with it. I ran the rs number through the gvs and looked at chr 12 region 110368991 - 110368991 which is quite a bit tighter than their parameters. In that short region there are 21 additional SNPs, 2 of which are in perfect LD (in the Caucasian population) with rs3184504. The other two SNPs are both in ATXN2.

They tested PBMCs from 56 Europeans and sorted their responses to stimuli based on the genotype at rs3184504. HOWEVER since they already showed that this SNP is in a long haplotype stretch, it's likely that these 56 people had a lot of other SNPs that varied consistent with rs3184504. This means that they were testing not only the effect of this SNP, but also all the others in the region (including the two I mentioned in perfect LD.

So until they refine their testing, maybe with transfections or something, they're still testing a region, not a gene.

There's a lot of other comments I could make, but that was the biggest one - isolating a region and claiming they were looking at a single gene.

[kareng]

Whoa, that last bit was so completely over my head! Lol

That's why we have Sky & Jess!

[saintmaybe]

There's a ton of stuff in high LD which could be related to some selection, or could be that chromosome just doesn't cross there.

The first paper you cited is interesting. They looked at a high ancestral coefcient to determine long haplotype stretches. rs3184504 SH2B3 was the highest with an Fst of .6 (higher than random drift) so they explored that gene further HOWEVER since they identified this with a long haploype (500kb) there are a bunch of other SNPs and genes that are dragged along with it. I ran the rs number through the gvs and looked at chr 12 region 110368991 - 110368991 which is quite a bit tighter than their parameters. In that short region there are 21 additional SNPs, 2 of which are in perfect LD (in the Caucasian population) with rs3184504. The other two SNPs are both in ATXN2.

They tested PBMCs from 56 Europeans and sorted their responses to stimuli based on the genotype at rs3184504. HOWEVER since they already showed that this SNP is in a long haplotype stretch, it's likely that these 56 people had a lot of other SNPs that varied consistent with rs3184504. This means that they were testing not only the effect of this SNP, but also all the others in the region (including the two I mentioned in perfect LD.

So until they refine their testing, maybe with transfections or something, they're still testing a region, not a gene.

There's a lot of other comments I could make, but that was the biggest one - isolating a region and claiming they were looking at a single gene.

Hm, interesting. So do you think the celiac phenotype itself is linked in a block or a region of genes that is under positive selection?

I ask, because celiac is not a lethal mutation from generation to generation, spontaneously arising, quite obviously. Nor does it prevent people from procreating under all circumstances, although there is good evidence of much lowered fecundity in female celiacs. I think the evolutionary picture might be a lot more complicated than the always positive, always negative, always neutral of the genetics textbooks.

Good arguments can be made that modern medicine and nutrition have relaxed the negative selection pressure on celiacs, *under the right circumstances.* That's a far cry from being positively selected, of course, but I'd be interested under what circumstances celiac disease might confer a survival or reproductive advantage outside of the context of modern science. Perhaps we can say it's drifting, right now?

(Why isn't there an emoticon for stroking my Darwin beard thoughtfully? I don't actually have a Darwin beard, seeing as I'm a woman,but they are endemic unfortunately in the graybeards of ecology departments)

[pricklypear1971]

Hm, interesting. So do you think the celiac phenotype itself is linked in a block or a region of genes that is under positive selection?

I ask, because celiac is not a lethal mutation from generation to generation, spontaneously arising, quite obviously. Nor does it prevent people from procreating under all circumstances, although there is good evidence of much lowered fecundity in female celiacs. I think the evolutionary picture might be a lot more complicated than the always positive, always negative, always neutral of the genetics textbooks.

Good arguments can be made that modern medicine and nutrition have relaxed the negative selection pressure on celiacs, *under the right circumstances.* That's a far cry from being positively selected, of course, but I'd be interested under what circumstances celiac disease might confer a survival or reproductive advantage outside of the context of modern science. Perhaps we can say it's drifting, right now?

(Why isn't there an emoticon for stroking my Darwin beard thoughtfully? I don't actually have a Darwin beard, seeing as I'm a woman,but they are endemic unfortunately in the graybeards of ecology departments)

This is completely out of my field; however, this is a thought....because I can't resist.....

Most plants and animals develop defense mechanisms to aid survival. Why couldn't Celiac (or DNA based gluten intolerance) be a defense mechanism of sorts - "don't eat this, it makes you sick"?

The Paleos will love that idea .

[mbrookes]

I am concerned that you let a jacka** like that upset you. If he had been a family member or close friend I can understand. He's just a jerk you see at work. Forget it!

[Skylark]

There's a ton of stuff in high LD which could be related to some selection, or could be that chromosome just doesn't cross there.

The first paper you cited is interesting. They looked at a high ancestral coefcient to determine long haplotype stretches. rs3184504 SH2B3 was the highest with an Fst of .6 (higher than random drift) so they explored that gene further HOWEVER since they identified this with a long haploype (500kb) there are a bunch of other SNPs and genes that are dragged along with it. I ran the rs number through the gvs and looked at chr 12 region 110368991 - 110368991 which is quite a bit tighter than their parameters. In that short region there are 21 additional SNPs, 2 of which are in perfect LD (in the Caucasian population) with rs3184504. The other two SNPs are both in ATXN2.

They tested PBMCs from 56 Europeans and sorted their responses to stimuli based on the genotype at rs3184504. HOWEVER since they already showed that this SNP is in a long haplotype stretch, it's likely that these 56 people had a lot of other SNPs that varied consistent with rs3184504. This means that they were testing not only the effect of this SNP, but also all the others in the region (including the two I mentioned in perfect LD.

So until they refine their testing, maybe with transfections or something, they're still testing a region, not a gene.

There's a lot of other comments I could make, but that was the biggest one - isolating a region and claiming they were looking at a single gene.

Your analysis makes sense. I think they picked out SH2B3 from that stretch of DNA partly on biological evidence. It codes for an adapter protein called Lnk that mediates cytokine receptor signaling. Lnk has also been implicated in Type 1 diabetes, and as we're well aware there is a propensity for people with Type 1 to also have celiac.

I loaded up genbank and looked at that region of the chromosome. It's hard to make any argument for ATXN2 involvement in celiac, particularly with the cytokine data in the paper. CUX2, FAM109A... who knows???

By the way, I'm sorry to be wandering off into geek-speak. I don't get to talk celiac science very often because it's not my main research. This is a rare indulgence so please forgive me and Jestgar.