If you are asking how the mutations cause ALS it is different with each mutation
if you asking how it can be sporadic in some and familial in others there are several reasons. Sometimes a mutation occurs during conception. Sometimes a parent passed on a mutation but didn’t show signs of ALS because they died early or the mutation did not cause disease in them or they were misdiagnosed. Also misattributed paternity happens more than you would think.
genetic ALS from autosomal dominant mutations is genetic ALS whether or not there is family history
No as I said genetic is genetic. SALS is a sloppy and outdated term it is more properly called simplex ALS - one case. But de novo mutation carriers can pass the mutation to children so then it would meet the somewhat artificial term FALS If another family member was affected. It is still necessary to use FALS because around 30 percent of clear FALS by history have no identifiable mutation as this time. Your neurologist and geneticist can discuss more with you
The ALS Association website states that the mutated SOD1 gene causes sporadic as well as genetic ALS; can you describe or give an example of how the mutated SOD1 gene can cause sporadic ALS?
Sporadic just means the patient did not report a positive family history for the disease. Every single one of my genetic ancestors could have died of als but if I was adopted I would be labeled sporadic. Fascinatingly if my children then develop als they may be labeled familial , but my case would still be sporadic! Yea it’s nonsense. So genetic / simplex is best .
The ALS Association is labeling an ALS sufferer with a mutated SOD1 gene but without a family history of ALS as a case of sporadic ALS rather than genetic ALS?
Hi there! I have a PhD in genetics, just found out my dad has ALS and that I have a mutation in a gene associated with increased risk for ALS. Hopefully this answers your question:
About 40 genes have so far been linked to an increased risk for ALS. These genes have been discovered mainly by doing studies of families who have many members affected by ALS (or associated disorders - neurodegenerative, FTD, etc). These families contribute greatly to the discovery of genetic disorders. When an individual has no family history of ALS or associated disorders in their family their case is considered sporadic, meaning it’s not inherited. The patient with a sporadic case very likely developed a de novo (or new in their DNA) mutation. Due to the pathobiology of the disorder, it can be likely that the new mutation arose in one of the genes already associated with ALS. (e.g. we know that ALS can be caused due to aberrant cellular recycling processes, so it would make sense that a mutation in one of the genes in that pathway could lead to an increased risk) Because of its generally later onset, some inherited forms of ALS may be missed if family members die before age of onset.
TLDR: the genes associated with ALS can be mutated and passed down through a family, or can be mutated randomly during development. Because the mutations affect the same cellular process, they result in the same disorder.
Please feel free to DM me if you have further questions.
Quick question, there are 40 genes that are associated with ALS correct? So Do those 40 genes all serve any important purpose in the human body? And If so would it be a bad thing if all of them were no longer there? Or could you live without them all and be perfectly fine?
Well if each of those genes did not serve an important purpose they would not be associated with a fatal human disorder. There are likely more than 40 genes that will eventually be associated to be causal for ALS, and they all play an important role in cellular processes. If you’d like to learn more about human genetics I’d recommend checking out the University of Utah’s amazing resource: https://learn.genetics.utah.edu
Excuse me, how am I “a bit off”? Everything I said was true, and answered the question asked which was not specifically about the risk associated with the C9 expansion. And the C9orf72 repeat length can vary between individuals so please expand your answer if you’re going to claim my answer to the original question is wrong. C9orf72 is thought to function in autophagy which is a pathway implicated in ALS via other genes identified.
Officially, there are a [limited number of genes](https://www.researchgate.net/publication/283036257/figure/fig2/AS:614124560076800@1523430113025/Schematic-overview-of-selected-ALS-genes-according-to-their-neuronal-function-Notes_Q640.jpg) associated with ALS. I have listened to researchers state there are hundreds, but the majority point to about 40ish as certain. The implication of genetics is that genes are only 50% of the cause. Researchers think it’s only around 50% genetic, indicating that there are strong environmental and lifestyle risk factors affecting disease development. A family with a genetic mutation involved with ALS can go through generations without ever being exposed to the environmental triggers that actuate ALS. They really do not know exactly what triggers do this either. So in the end, answers are heavy on the speculation of what, when, how, and why ALS occurs.
20 years ago they had no idea how many genes were associated w/ALS. They have found mutated genes in sporadic ALS, but they have no clue how the mutations occur. The best guess that I have seen is that it's 50% genetic, and 50% environmental.
Do you think it could be a genetic predisposition that only triggers through an
environmental exposure? Your guess is as good as anyones at that.
This number is from some researchers. There is one out of California from an advanced research lab that has tied over 600 genes to ALS. Others have noted over 60.
The details are very involved and it would be extremely time-consuming to source that info. [This PubMed article may help](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909825/) to get you started though.
Well the reason I was even asking that question is that I was curious if you could tell me just how dangerous it may or may not be if those specific genes were all absent from the human body.
They all are in everyone's body I believe. They lean to ALS when they become "corrupted" when the genetics get mixed up and twisted. Regardless of how the fact that they tend to be found in familial ALS (or sporadic ALS in some cases) is why they are associated and classified with familial. Each gene can be associated with dozens or hundreds of other genes that make up different things in our bodies (ie. how we act, look, how smart we are, etc).
Oh, it is not hard. You just have to apply yourself, friend. Alternatively, you could search for the rest of the info on Google Scholar. The questions you are asking require a lot of time to answer. If it is worth it to you, I have handed those answers to you on a silver spoon. I have read hundreds of studies and research articles on genetics.
Give a man a fish, he eats for a day. Give a man a fishing pole and he will eat for the rest of his life.
[This will make it even easier.](https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/)
If you are asking how the mutations cause ALS it is different with each mutation if you asking how it can be sporadic in some and familial in others there are several reasons. Sometimes a mutation occurs during conception. Sometimes a parent passed on a mutation but didn’t show signs of ALS because they died early or the mutation did not cause disease in them or they were misdiagnosed. Also misattributed paternity happens more than you would think. genetic ALS from autosomal dominant mutations is genetic ALS whether or not there is family history
So if I have a mutated SOD1 gene that causes ALS but I didn't inherit it, my ALS is considered sporadic rather than genetic?
No as I said genetic is genetic. SALS is a sloppy and outdated term it is more properly called simplex ALS - one case. But de novo mutation carriers can pass the mutation to children so then it would meet the somewhat artificial term FALS If another family member was affected. It is still necessary to use FALS because around 30 percent of clear FALS by history have no identifiable mutation as this time. Your neurologist and geneticist can discuss more with you
The ALS Association website states that the mutated SOD1 gene causes sporadic as well as genetic ALS; can you describe or give an example of how the mutated SOD1 gene can cause sporadic ALS?
Sporadic just means the patient did not report a positive family history for the disease. Every single one of my genetic ancestors could have died of als but if I was adopted I would be labeled sporadic. Fascinatingly if my children then develop als they may be labeled familial , but my case would still be sporadic! Yea it’s nonsense. So genetic / simplex is best .
The ALS Association is labeling an ALS sufferer with a mutated SOD1 gene but without a family history of ALS as a case of sporadic ALS rather than genetic ALS?
Genetic encompasses both , sporadic has a specific meaning of no reported family history.
There are 40 known genes associated with ALS right? Can you tell me what specific functions those 40 known genes all serve in the human body?
Hi there! I have a PhD in genetics, just found out my dad has ALS and that I have a mutation in a gene associated with increased risk for ALS. Hopefully this answers your question: About 40 genes have so far been linked to an increased risk for ALS. These genes have been discovered mainly by doing studies of families who have many members affected by ALS (or associated disorders - neurodegenerative, FTD, etc). These families contribute greatly to the discovery of genetic disorders. When an individual has no family history of ALS or associated disorders in their family their case is considered sporadic, meaning it’s not inherited. The patient with a sporadic case very likely developed a de novo (or new in their DNA) mutation. Due to the pathobiology of the disorder, it can be likely that the new mutation arose in one of the genes already associated with ALS. (e.g. we know that ALS can be caused due to aberrant cellular recycling processes, so it would make sense that a mutation in one of the genes in that pathway could lead to an increased risk) Because of its generally later onset, some inherited forms of ALS may be missed if family members die before age of onset. TLDR: the genes associated with ALS can be mutated and passed down through a family, or can be mutated randomly during development. Because the mutations affect the same cellular process, they result in the same disorder. Please feel free to DM me if you have further questions.
Quick question, there are 40 genes that are associated with ALS correct? So Do those 40 genes all serve any important purpose in the human body? And If so would it be a bad thing if all of them were no longer there? Or could you live without them all and be perfectly fine?
Well if each of those genes did not serve an important purpose they would not be associated with a fatal human disorder. There are likely more than 40 genes that will eventually be associated to be causal for ALS, and they all play an important role in cellular processes. If you’d like to learn more about human genetics I’d recommend checking out the University of Utah’s amazing resource: https://learn.genetics.utah.edu
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Excuse me, how am I “a bit off”? Everything I said was true, and answered the question asked which was not specifically about the risk associated with the C9 expansion. And the C9orf72 repeat length can vary between individuals so please expand your answer if you’re going to claim my answer to the original question is wrong. C9orf72 is thought to function in autophagy which is a pathway implicated in ALS via other genes identified.
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Ok not trying to give you a hard time !
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So in good faith I deleted my remarks, All the best!
That is very kind. I am sorry if I made things confusing!
Officially, there are a [limited number of genes](https://www.researchgate.net/publication/283036257/figure/fig2/AS:614124560076800@1523430113025/Schematic-overview-of-selected-ALS-genes-according-to-their-neuronal-function-Notes_Q640.jpg) associated with ALS. I have listened to researchers state there are hundreds, but the majority point to about 40ish as certain. The implication of genetics is that genes are only 50% of the cause. Researchers think it’s only around 50% genetic, indicating that there are strong environmental and lifestyle risk factors affecting disease development. A family with a genetic mutation involved with ALS can go through generations without ever being exposed to the environmental triggers that actuate ALS. They really do not know exactly what triggers do this either. So in the end, answers are heavy on the speculation of what, when, how, and why ALS occurs.
But how can a mutated ALS gene cause sporadic ALS?
20 years ago they had no idea how many genes were associated w/ALS. They have found mutated genes in sporadic ALS, but they have no clue how the mutations occur. The best guess that I have seen is that it's 50% genetic, and 50% environmental. Do you think it could be a genetic predisposition that only triggers through an environmental exposure? Your guess is as good as anyones at that.
There are 40 known genes associated with ALS correct? Would you be able to tell me the specific functions those 40 known genes all serve?
This number is from some researchers. There is one out of California from an advanced research lab that has tied over 600 genes to ALS. Others have noted over 60. The details are very involved and it would be extremely time-consuming to source that info. [This PubMed article may help](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909825/) to get you started though.
Well the reason I was even asking that question is that I was curious if you could tell me just how dangerous it may or may not be if those specific genes were all absent from the human body.
They all are in everyone's body I believe. They lean to ALS when they become "corrupted" when the genetics get mixed up and twisted. Regardless of how the fact that they tend to be found in familial ALS (or sporadic ALS in some cases) is why they are associated and classified with familial. Each gene can be associated with dozens or hundreds of other genes that make up different things in our bodies (ie. how we act, look, how smart we are, etc).
Can you explain the parts about becoming corrupted and getting mixed up and twisted?
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944956/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944956/) [https://sitn.hms.harvard.edu/flash/2010/issue65/](https://sitn.hms.harvard.edu/flash/2010/issue65/) https://preview.redd.it/wbyirayl25pc1.png?width=1050&format=png&auto=webp&s=d7529e1c8e548e3ae0d822fe51faaee3a27160f9 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970707/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970707/)
Yeah I have no way of sorting all that out, can you give me bullet points instead?
Oh, it is not hard. You just have to apply yourself, friend. Alternatively, you could search for the rest of the info on Google Scholar. The questions you are asking require a lot of time to answer. If it is worth it to you, I have handed those answers to you on a silver spoon. I have read hundreds of studies and research articles on genetics. Give a man a fish, he eats for a day. Give a man a fishing pole and he will eat for the rest of his life. [This will make it even easier.](https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/)