You might be interested in this paper: https://www.frontiersin.org/articles/10.3389/fgene.2011.00100/full

Outlines in vivo studies in mice showing how Ras zygosity effects tumour identity differently based on the type of mutation they've got. While Ras knockouts seem to make fetuses unviable, Ras Gain-of-function seems to still permit viability, but also confers shorter lifespans because of tumours.

A lot of Ras mutations are acquired from what i know, with different mutations being linked more to certain organs because of the nature of carcinogens that organ is exposed to. So I don't know if it's super worth looking deeper into heredity of this sort of thing, even if its very cool.

[removed]

Almost as terrifying as visiting a Wuhan live market in November 2019 and then two weeks later half of your household is in either the ICU or dead.

As long as there was some precipitation during the year. IIRC, the one assumption we have to make is that there was SOME precipitation for most years on Antarctica. Which doesn't seem unreasonable.

In vivo I think this will require consanguinity to produce someone who has homozygous ras mutations as these are fairly rare disorders with severe effects in heterozygotes. Also, they aren't concentrated in particular endogamous populations as far as I know.

In vivo we have to additionally ask if a fetus would be viable with homozygous ras pathogenic variants. Heterozygosity may reduce viability of fetuses with related genetic diseases.

Search for https://www.ncbi.nlm.nih.gov/nuccore/?term=Ebolavirus%5Borganism%5D+AND+bat on genbank you'll find two batches of bat ebolavirus sequences: one 2019 paper https://pubmed.ncbi.nlm.nih.gov/31002301/ sequencing full Bombali ebolavirus genomes from bats, this study is considered trustful and indicates a bat origin of Bombali. This is also confirmed independently by some Predict sequences such as https://www.ncbi.nlm.nih.gov/nuccore/MT929359.1

And another 2005 paper https://www.nature.com/articles/438575a using nested PCR to obtain short partial Zaire ebolavirus (the genuine Ebola) sequences. This hasn't been replicated since 2005, this paper is not considered trustful.

There is a similar nested PCR story for Reston ebolavirus https://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0331-3 but they didn't bother to upload the sequence to genbank..

Still Marburg (a distant filovirus) also has a clear bat origin.

Together with the serological studies and the lack of other putative reservoir it means that fruit bats are still our best guess.

But the truth is that we don't know for sure.

[removed]

So essentially for fatigue, the repetitive localized micro-plastic deformations, will keep shifting/form the slip bands until the straw breaks the camels back?

Could repetitive elastic deformation cause fatigue? My gut thought is that by defenition it can't? Basically if it does, it is actually micro plastic deformation and not elastic deformation.

[removed]

Yes fair, just meaning to clarify that the phrase exceedingly improbable is a bit inaccurate since there are a huge amount of examples of disorders that work this way in reality.

The first time I read about kitum cave I was scared shitless. Imagine not knowing about it and exploring it.

Those are exceptions rather than the rule for rare disease. Ashkenazi Jews had a bottleneck effect; SSD is a gain of function, etc. They other thing they have in common is a relatively high allele frequency in the general population.

For interference where a heterozygote would be effected (and therefore selected again) most variants would be de novo; so a homozygous mutant would require simultaneous and identical de novo mutations to occur in the same individual.

Sort of. Protocadherins are like address codes in the developing brain. So the problem is having 2 different sets of instructions for migrating neurons. Hence heterozygotes have disease and homozygotes (even if mutant) are normal. even if co-expressed absent mosiacism the prediction would be disease. However, for reasons I mentioned in the original post human examples would be hard to find because the event of 2 identical yet independent mutations would be highly improbable.

In diseases with recurrent mutations there is usually a mechanistic reason (Gain of function in achondroplasia) that wouldn't apply here.

Here is an even older paper describing this before we found any examples.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1686061/

That’s not true, there are many AR conditions with common pathogenic carrier mutations which mean that many affected individuals are absolutely homozygous without any consanguinity.

It’s not exceedingly improbable at all. Examples off top of my head are delta f 508 for Cystic fibrosis, all the ashkenazi Jewish common AR conditions, SMA, sickle cell disease, alpha thal, beta thal, and I’ve personally seen many patients with other disorders who are affected and homozygous for same pathogenic variant.

[deleted]

The problem is in the interaction. If you imagine the "normal" X chromosome (let's call it N), and the "bad" X chromosome (B), then a network of entirely B cells or entirely N cells works fine, since they're all on a standard "protocol" if you will.

However, if you undergo X inactivation in an individual that has BN genetics (one copy of each), then you get some clusters of cells with each type - And at the interface between B and N you get weird, glitchy behavior that can cause symptoms like seizure because they aren't quite fully compatible with one another.

At least, assuming I understood correctly.

Oh no, I thought (and taught) that one of the two X chromosomes gets packed away in the Barr body. Do both X chromosomes add to the exogne of the cell, or is the problem an interaction between cells?

Yes.

Not particular to your question, but genetic combinations determining sex categorisation- ideally one turns out either phenotypically male or female in regards to a particular species in sexually reproducing organisms and this takes place at some point during fertilisation & early developmental stages(in vitro of maternal parent).

An individual that turns out with an in-between combination of the two (Hermaphrodite) is likely sterile/infertile, may have low function in the less developed organ system which may or not be a problem except there’re associated urinogenital complications, and in humans puberty is affected by two sets of hormone cycles that synergistically have regressive effects on the individuals body physiology and overall development curve(mental retardation & stunted physical growth are also witnessed in certain severe cases)

It presents with different allele-combinations and is a very rare condition because plenty times the zygote is not viable at all. Do all individuals with this suffer the above traits? Realistically speaking, we’re not in a position to form an opinion of that as a fact- they seemingly can lead normal lives but that’s only the lesser part of an already small case group.

[removed]

This is how I interpreted it as well. The issue is more of the mosiaic distribution of the different tissue. It ends up patchy like a tortoise shell cat's fur.

[removed]

Yes, this can happen and is known as underdominance and is a specific type of epistasis (which is a more complex, but more realistic view of the interaction between alleles than the simple dominant/recessive model that is taught in intro biology). The thing is, if the disease is severe, then selection will be very strong against heterozygotes. If the population is otherwise freely mixing, whichever allele is less common would pretty quickly get removed, so such examples will never be common. If the alleles segregate among sub-populations that don't mix freely, then this kind of thing is likely a contributing factor to speciation (see the Dobzhansky–Muller model, though if you want to look at the most current research on this idea, "cryptic variation" is the umbrella term that you should use)

[removed]

Right, which is why they probably use potassium or krypton instead of carbon. I'm just not as familiar with their isotopes or halflives which is why I used carbon in my example.

How close is nearby? It's thought that SN 1054 (Crab Nebula) is the same object as a "guest star" observed by Chinese astronomers in 1054-1056, and that's about 6500 lys away, so relatively close by.

It started as being invisible to the human eye, then went through a process of becoming much brighter before dimming again over a ~2 year period. So much brighter that it was visible in daylight for about 23 days, according to one account.