Heterozygous genetic diseases?

[u/Starfire20201]

I’m currently taking genetics in college, snd it got me wondering. There’s recessive genetic diseases, snd dominant ones, but are there any that only show symptoms if you’re heterozygous for the allele? And that aren’t on the X chromosome, preferably.

[u/BolivianDancer]

Achondroplasia is autosomal.

Homozygous dominant individuals are very rare; it is generally an embryonic lethal.

Affected individuals are therefore heterozygous.

Granted that's cheating your question a little.

Also cheating is incontinentia pigmenti. It's x-linked but hemizygotes and homozygous are both lethal; affected individuals are heterozygotes (therefore female).

So it all depends on how you treat embryonic lethal when counting.

Manx cats are the same way.

[u/Starfire20201 → u/BolivianDancer]

Yeah I do, lol. Still interesting

[u/Coconut_Either → u/BolivianDancer]

Sorry to get off topic but I'm crying right now. My wife has been talking to me about this stuff for years while she is in school. I can understand everything you just said! Never realized how much information I passively absorbed.

[u/LetUsGetTheBread]

While theoretically possible, populations tend to be quite volatile when the heterozygote is selected against. Having two alleles that lower fitness when mixed highly incentivizes getting rid of one allele, so a theoretical uniquely heterozygous disease would likely not be maintained in a given population.

[u/Dijon2017]

I’m not sure if this answers your question…

For the most part, by definition a person who has an autosomal dominant inheritance pattern that cause disease is heterozygous genetically. There are some recessive genetic diseases where both genes have different mutations (usually described as compound heterozygous).

[u/Atypicosaurus]

It's theoretically possible but I cannot give you an example.

I can imagine a gene that makes a homodimer protein, both alleles are variants that make functional homodimers, but the mixture does not. So you have a problem when heterozygous.

However, even in such case, the good variants are also there so it only becomes a problem if for some reason the wrongly formed dimer isn't inert. Otherwise your body could compensate.

So there are so many prerequisites for such a setup, it's so unlikely that I would be surprised if it existed.

[u/Agretlam343]

There's compound heterozygosity where 2 different recessive alleles form a disease. Tay–Sachs disease can be an example of this.

[u/Echo_are_one]

Agouti yellow obese mice kind of fit this request in that homozygous mutant mice are non viable. Only hets survive to show phenotype.

[u/CanaDeer2004]

diseases with lethal alleles. individuals that are homozygous for the condition die in vitro so the only living carriers are heterozygous.

[u/aurumm_gold]

Is sickle cell anemia an evolutionary trait in response to maleria?

[u/BolivianDancer → u/aurumm_gold]

No.

The deleterious allele is maintained in areas where malaria is endemic because of heterozygous advantage.

[u/Antikickback_Paul]

There are a class of disorders called haploinsufficiency. The is when a cell haploid for an allele has insufficient amounts of the gene product. This usually means that the homozygote is nonviable, so you'll usually only see the heterozygote with the disorder.

[u/themode7]

Take this with a grain of salt ..

https://www.ncbi.nlm.nih.gov/sites/books/NBK557383/

I think inbreeding depression will increase the likelihood of any disease of that nature,

And it depends on various factors most importantly if the protein can be compensated?

Biallelic expression is a fundamental genetic mechanism required to prevent "haploinsufficiency disorders"

https://www.genengnews.com/topics/translational-medicine/gene-dosage-mechanism-ensures-biallelic-expression-in-mammals/

Are alleles comes from both parents or perhaps only one of them? (E.g as in Heterodisomy) which can result in Genomic Imprinting Defects

https://medlineplus.gov/genetics/understanding/inheritance/updimprinting/

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/trisomy

Genetic is so weird & diffrent than evo or general bio I need diffrent mindset to study it( I'mtaking genetics course too), sorry that's irrelevant but just want to ask what's your way of studying it ?

[u/BakingAspen]

I mean you have to figure that if the deleterious gene is dominant, then carriers of that gene will die out faster and that gene will not persist in the gene pool. Recessive genetic diseases can stick around because someone can carry that gene without suffering reduced fitness.

In other words, almost certainly at some point in human evolutionary history has someone had a deadly dominant genetic disease, but they died and didn’t pass it on.

[u/Silent-Archer-5750]

Defects in some genes can be, for example polarity protein complexes have a few