Pleiotropy

[seminoma]

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FA definition "One gene contributes to multiple phenotypic effects". Example given is PKU --> light skin, mental ******ation, musty body odor.

Don't all genes contribute to multiple phenotypic effects? I can't think of one mutation that results in a single phenotypic finding.

 

[dfib slim]

FA definition "One gene contributes to multiple phenotypic effects". Example given is PKU --> light skin, mental ******ation, musty body odor.

Don't all genes contribute to multiple phenotypic effects? I can't think of one mutation that results in a single phenotypic finding.

The phenotypic effects have to appear unrelated to each other.

 

[seminoma]

The phenotypic effects have to appear unrelated to each other.

So what's an example of a mutation that is non-pleiotropic? Depending on who you talk to all phenotypic effects are related (if you draw enough arrows).

 

[dfib slim]

So what's an example of a mutation that is non-pleiotropic? Depending on who you talk to all phenotypic effects are related (if you draw enough arrows).

Maybe something like sickle cell. All the effects, functional asplenia, vaso-occlusive crisis, hemolytic anemia, are all related to the sickling of the RBC and confined to the cardiovascular system.

With pleiotropy I think of something like Marfans. You have symptoms spread out over different systems like skeleton, heart, and eyes so the different phenotypic manifestations seem unrelated.

 

[sloop]

FA definition "One gene contributes to multiple phenotypic effects". Example given is PKU --> light skin, mental ******ation, musty body odor.

Don't all genes contribute to multiple phenotypic effects? I can't think of one mutation that results in a single phenotypic finding.

The annoying thing with testing genetics is that you basically have to make a judgment call on these types of definitions because most terms relating genotype and phenotype depend entirely on the level to which that you're evaluating something. One example of this is penetrance vs variable expressivity: Depending on whether you define penetrant as having the full spectrum of symptoms associated with a disease or having any manifestation associated with the disease, you can get different answers to a question asking whether an example demonstrates incomplete penetrance or variable expressivity (generally the boards define penetrance in a binary way of "you either have the disease or you don't"). The reality is that these terms are constructs that probably describe different manifestations of the same phenomenon—most genes probably have a dose range through which individuals will exhibit a spectrum of "subclinical" symptoms but for some this range is more narrow than others and individuals typically either show the full phenotype or do not.

I think the concept of pleiotropy has the same linguistic issues. Most genes do have multiple phenotypic findings. Depending on how particular you're being with distinguishing between phenotypic findings you can get different answers. As has already been mentioned, I think that the boards will generally consider two phenotypic findings as the same if they are concretely related to the same underlying pathophysiological process. I also thought about Sickle Cell as an example, but I see it's already been mentioned so I'll use another example.

Most people would not consider the findings of thick mucoid sputum and bronchiectasis in CF to be an example of pleiotropic effects. Most people would consider the findings of thick mucoid sputum and congenital absence of the vas deferens in CF to be an example of pleiotropy.

Like I said, it starts becoming a judgment call if you ask whether bronchiectasis and cystic pancreatic dilatations in CF are examples of pleiotropy. That largely depends on how specifically you're defining your phenotype: If it's "thick mucoid secretions" then no, if it's "thick secretions in lungs" and "thick pancreatic secretions" then yes. In either case, I think they'll probably try to give clear examples and if it's multiple choice, there usually isn't another answer that would explain findings when they're trying to get at pleiotropy.

If they're giving you multiple arguably divergent phenotypic findings and asking you what it's an example of, 99% of the time they're looking for pleiotropy even if you think it's ambiguous.

 

[seminoma]

Maybe something like sickle cell. All the effects, functional asplenia, vaso-occlusive crisis, hemolytic anemia, are all related to the sickling of the RBC and confined to the cardiovascular system.

With pleiotropy I think of something like Marfans. You have symptoms spread out over different systems like skeleton, heart, and eyes so the different phenotypic manifestations seem unrelated.

Thanks for the input. I guess it's just a matter of figuring out how unrelated things really are. If you ask me, all of Marfan symptoms are related since it's just the contribution fibrillin makes in various tissues. Same as sickle cell, which is initially all due to vasooclusion but eventually includes tons of stuff like osteomyelitis, acute chest syndrome, papillary necrosis, etc.

@sloop I think that's a good way to think about it.. maybe particular traits of a given disease are pleiotropic, but the disease itself doesn't necessarily have 100% pleiotropic effects.

 

[pd1112]

The key is one gene/mutation involving a pathway at the cellular/molecular level that affects multiple phenotypes spread out across different systems that would seem unrelated if you did not know the underlying mechanism. The usual examples are PKU, Marfan, CF, sickle cell, osteogenesis imperfecta, albinism. Think of it more of a historical term from the 19th-early 20th centuries when they didn't have anywhere near the knowledge of the genome & molecular biology. Marfan was described in 1896; the gene was found in 1991. Take a close look at the mutations too, because a lot of them involve a defect in a chromosome that actually affects multiple genes. I agree though, it is pretty confusing. But I think if you know those 6 that are the typical examples of pleiotropy, you'll be good.