/sci/ - Science & Math

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>>12680101
person have many chromosones, made of DNA
each chromosome have many genes, sequences of dna
person have two versions of each chromosome, one from mommy, one from daddy
person have two versions of each gene, one from mommy one from daddy
homozygous for a gene means mommy and daddy copy same (oversimplification but enough for this explanation)
heterozygous mean mommy and daddy copy different
mutations in genes can cause diseases
recessive means need two bad copies of gene for dieases
dominant means need only one bad copy of gene for disease
you probably won't have any effects from the disease since you only have one bad copy of gene
kids might if sexual partner has bad copy of gene

That explanation was sort of condescending but I'm drunk so cut me some slack. Also probably no one else will write you a good explanation so you're welcome.

>>12680126

> You probably won't have any effects from the disease since you only have one bad copy of gene

Let me emphasize in OP

> For a disease that I have

Hence my question, basic biology dictates that it should be classified as a dominant mutation. So far, I have been unable to find an answer, because nearly every source parrots the Biology 101 explanation.

>>12680101
Where did you find those results? I have ancestry DNA done, but I don't know where or how to find any diseases I have.

>>12680169
Dominant and recessive are simplifications. You probably have a mild form of the disease, yes?

So think about it this way. You have two copies of a gene in a normal person producing a normal amount of this protein. But now one of the copies is fucked. This means that you will still retain a majority healthy function because you have a working protein, but with the caveat that you are having to work twice as hard to purge all this extra bullshit you are producing.

It would help if you named the disease.

>>12680101
Well either the test results are wrong or our collective understanding of genomics is. I think the probability distribution tilts to the former although not by much

>>12680193

I had a genetic diagnostic test performed ordered by my doctor. I've never had an ancestry test done but I imagine they don't catch everything, in my case I had my disease narrowed down and they analyzed about 100 genes.

>>12680194

> Dominant and recessive are simplifications. You probably have a mild form of the disease, yes?

Relatively speaking.

So think about it this way. You have two copies of a gene in a normal person producing a normal amount of this protein. But now one of the copies is fucked. This means that you will still retain a majority healthy function because you have a working protein, but with the caveat that you are having to work twice as hard to purge all this extra bullshit you are producing.

This is what I suspected, but what's causing the recessive gene here to not be entirely masked as they usually are?

What's also interesting to me is that there's wildly different reported phenotypes of just my variant, someone with my variant had it much more severely than I did and died

Disease is congenital myopathy caused by COL VI mutation (Ulrich/Bethlam)

>>12680235
Reading about that disease a little bit, it sounds like it's more of a spectrum disorder than a strick dominant/recessive Mendelian disorder. Your doctor might have just been kind of a prick and oversimplifying things. I've had doctors like that. Was your doctor just a doctor or a genetic counselor?
>You have two copies of a gene in a normal person producing a normal amount of this protein. But now one of the copies is fucked
Based on like 45 seconds of reading this seems correct. It's not REALLY recessive disease if you have symptoms. If it were recessive then you wouldn't notice it. But I'm not sure your body is really purging anything. You just have a defective form of collagen that's getting used by cells and making things defective, but you still have the normal one too.

You might want to see a genetic counselor, they might be able to point you in the right direction. If your condition is bad, there even might be experimental genetic therapies for this kind of thing. I've had classes that talked about experimental therapies for other muscular dystrophies. I'm not a doctor though, just a bio grad.

>>12680262

> Was your doctor just a doctor or a genetic counselor?

It was the official genetic report that stated it's recessive. Doc's pretty cool, it was actually the genetic counselor present who gave me the non-answer but I didn't bother specifying that in the OP. She was too busy trying to preach to me the benefits to being cuckolded (sperm donation) when I tried asking about IVF so I kinda tuned her out.

> If it were recessive then you wouldn't notice it. But I'm not sure your body is really purging anything. You just have a defective form of collagen that's getting used by cells and making things defective, but you still have the normal one too

As I understand it, the defective form is effectively purged. The mutation either results in incomplete or absent protein, and if it's the former case it doesn't even form the whole COL VI molecule which is a trimer formed by 3 genes.

> If your condition is bad, there even might be experimental genetic therapies for this kind of thing.

I'm in the U.S. and I've looked into volunteering for clinical trials but basically none exist except in Europe, for some reason most of the research of this disease is outside of the U.S., there's a lot more focus on Duchennes and such.

>>12680328
Yeah Duchenne was the one my professors loved to talk about. Sorry anon, you probably know more about your disorder than anyone here. There's such a thing as incomplete dominant/recessive traits (I think that's what they were called) and that's probably what you have, as in it would be way worse if you were homozygous. I have no idea what your daily life is like and how bad your condition is, but I can tell you that you have to make these decisions on your own and that no one will understand what you're going through better than you. People here can explain textbook biology to you and doctors can recite what they've memorized in med books, but it's your condition. Maybe try going to Europe? I don't know.

Best of luck to you though. I hope it's not too bad.

>>12680101
I have good and bad news. You will understand it better than any geneticist. The whole field essentially imploded. There is a bus load of exceptions for everything. Probably the best thing is to look at ways to make the symptoms less severe. It can be everything from spiritual, meditation, nutrition, exercise and reducing environmental stressors.
Good health and good luck. You need to believe in yourself and your body.

>>12680101
>>12680235
>>12680328
Bumping to post later.

>>12682612
I will also look at the literature. I hope it stays alive.

>>12682612
>>12680101
>>12680235
>>12680328
Ok finally done seeing patients.

So one thing to say is just because you're a carrier doesn't mean you can't present with symptoms. For example, the most famous example is sickle cell trait leading to hyposthenuria.

The next thing is genetic disorders that deal with structural elements like collagen often have a characteristic known as dominant negative mutations where the ineffective/abnormal gene product from the recessive allele can cause a detriment to the function of the wild-type allele's gene product. Common example is osteogenesis imperfecta. I read up on COL6A1/2/3 mutations and they show this dominative negative characteristic as well.

You likely have Bethlem myopathy because it's the milder form and you are probably not less than 13 posting on 4chan because it's naughty and Ulrich's causes kids to be wheel-chair bound in their first decade of life.

Bethlem myopathy has shown to have autosomal dominant, autosomal recessive, and compound heterozygous mutations as well (COL6A2 predominantly). Compound heterozygous means having two different mutated alleles leading to disease which can sometimes show up as autosomal recessive in basic tests.

So the reason for your test result is
A) the test associated the gene with Ulrich's and auto gave you an AR result even though you might not be
B) test associated mutation with a known Bethlem myopathy mutation that is AR but you actually have the AD version
C) you have an AR mutation but dominant negative phenotype leading to presentation of disease
D) you have a compound heterozygote condition which was read as AR

I think C and D are more likely.

(1/2)

>>12683791
>>12680101
>>12680235
>>12680328
Here are my sources and resources for you:
https://pubmed.ncbi.nlm.nih.gov/11381124/
https://pubmed.ncbi.nlm.nih.gov/11992252/
https://pubmed.ncbi.nlm.nih.gov/12840783/
https://pubmed.ncbi.nlm.nih.gov/15563506/
https://pubmed.ncbi.nlm.nih.gov/16130093/
https://pubmed.ncbi.nlm.nih.gov/16141002/
https://pubmed.ncbi.nlm.nih.gov/29419890/
https://pubmed.ncbi.nlm.nih.gov/17886299/
https://pubmed.ncbi.nlm.nih.gov/25535305/
https://pubmed.ncbi.nlm.nih.gov/19949035/
https://pubmed.ncbi.nlm.nih.gov/31471117/
https://pubmed.ncbi.nlm.nih.gov/20976770/
https://pubmed.ncbi.nlm.nih.gov/29894794/
https://www.egl-eurofins.com/tests/?testid=DC6A3
https://rarediseases.info.nih.gov/diseases/4769/ullrich-congenital-muscular-dystrophy
https://rarediseases.info.nih.gov/diseases/873/bethlem-myopathy
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=75840&lng=EN
https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=367
https://omim.org/entry/158810
https://omim.org/entry/616471
https://omim.org/entry/254090
https://omim.org/entry/616470
https://medlineplus.gov/genetics/condition/collagen-vi-related-myopathy/
https://rarediseases.org/rare-diseases/collagen-type-vi-related-disorders/

(2/3 now...)

>>12683837
>>12680101
>>12680235
>>12680328
If you have any other questions, I hope these links can help. If you need help with them let me know. If you want to talk to a young resident interested in these types of disorders, I would be interested. Do you have a discord?

Also would you be willing to share some information regarding your history. Like what are your symptoms, how did you present, why did they think of a genetic disorder and what genes to test.
I would be very interested.

Thanks for letting me know about this disorder OP. Lots of these orphan diseases need more awareness.
Maybe you would also like these groups to talk to people with similar conditions?
https://strongly.mda.org/
https://musculardystrophynews.com/
https://www.musculardystrophyuk.org/
https://www.curecmd.org/support-groups (even has a Bethlem support group bc I know most of these will cater to DMD/Becker)

Best of luck OP. Thanks again and hope things go for the better. Hope gene therapy can one day make these sorts of conditions never exist.

(3/3)

>>12683791
>>12683837
>>12683846
Just gonna bump this so the thread stays alive for OP to see.
If someone is willing to keep this thread alive while I go get some rest, I'd appreciate it.
Thanks.

>>12680101

>Bum nigga. Talk to me nice pussy. I'll slap the shit out of you bitch, word to my mums nigga.

bump

>>12684517
Bump

>>12680194
>>12680169
A lot of things in genetics isn't in binary (recessive/dominant) but is on a spectrum with various degrees of effectiveness where one side weighs down slightly more or completely in correlation with the severity of the said mutation.

>>12684141
OP still hasn't showed up huh.
Maybe he'll see this somehow in the future.
I'll be in /med/ from time to time if you're willing to go into detail regarding your history.

>>12683791
>>12683837
>>12683846

OP here, appreciate your response. I saw it soon after you posted but got a 24h ban. I'm out right now but will respond in a bit.

>>12683791
>>12683837
>>12683846

The dominant negative mutation explanation makes a lot of sense. I can rule out D) since genetic testing would have likely caught another mutation.

> If you have any other questions, I hope these links can help. If you need help with them let me know. If you want to talk to a young resident interested in these types of disorders, I would be interested. Do you have a discord?

Feel free to reach out at Thorium#8725

I'd be happy to answer your questions. I also have other questions I'd like to ask that are a bit hard to answer through my own research that you could perhaps you could answer and fill some of the gaps in my understanding. I can read and digest the scientific literature with some effort but that doesn't always give you a complete picture of the state of the field. I'd be interesting in discussing some avenues of potential therapies I've read about and what limitations/obstacles there are in bringing them to fruition.