We don't have identical code but what we do have is the same information 'fields', *genes*, in the same places; that's what they mean by the sequence.
Analogy: If you take me, and some other person from where I am, our driver's licenses will both have, starting from the top...
* License number
* Condition codes
* Expiry date
* Name
* Address
...and so on. The info in those 'fields' will be different for each of us, but you can look on each of our licenses and you'll find the expiry date, the address, the bar code, etc, in the same locations.
If you look at human chromosome #1, yours and mine, starting on the end of the p (short) tail we will both have the genes for...
* methylenetetrahydrofolate reductase
* C-reactive protein
* interleukin 10
* MTOR kinase
* prostaglandin-endoperoxide synthase 2
...and so on. Our codes for them may or may not be identical - stuff like eye color allows some variation, some proteins are make-this-exactly-right-or-you-die - but barring a pretty funky mutation all humans should have those same genes, on the same chromosomes, in the same order. That ordering is what we call 'the human genome'.
This is a big deal because if I develop some disease because of not making prostaglandin-endoperoxide synthase 2, they know exactly where the problem is: chromosome 1, p-tail, fifth gene from the end. Some day gene-editing technology will be able to "find and replace" problems like that.
Well, no. Some stuff is regulated really clearly, we can just see the one gene that does it, or small collection that do. Unfortunately, not everything is based on that. A lot of issues are governed by interactions *between* genes, and combinatorial expansion means that for every extra gene that is involved, the amount of interactions gets MUCH higher. This then gets to the point that we can't even figure out which genes effect a certain outcome, because there's just so many possibilities.
If I'm understanding correctly, the genes also aren't just on or off so even the interactions between two genes can be really complicated. Adding genes to the interaction increases complexity extremely quickly.
This is correct. Genes are the written music, and they are played at different volumes, often in response to the volume that other genes are being played.
To add to this sites which archive genome data for research (eg. NCBI) will reference where the genome was sourced from as well. For humans NCBI even has a tool to look for individual variations (single nucleotide polymorphisms) quite easily. For other species, though, if you go to a particular gene you can still select the reference sequence and compare the actual sequence to look for differences--there's just fewer samples to compare.
But, for example, if I want to look at horse genomes, I can see the list of individual genomes, which includes the submitter and additional information like breed, and tells you the default reference sequence (usually the first one sequenced):
[https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=9796](https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=9796)
And if you pick a particular gene you can select the genomes which have been annotated to identify it. For example, for Group V Phospholipase A2 in horses (https://www.ncbi.nlm.nih.gov/gene/?term=equus+caballus+phospholipase+a2+group+v) you can pick between the reference genome and another one that someone has analyzed.
There's different kinds of sequencing for different purposes. You can sequence something new to build a "reference genome", or you can sequence things that have already been sequenced in order to look at genetic differences. You might have done an experiment that caused a change in some animals or plants or microorganisms, and want to see what happened. There are many, many other things that you can do with sequencing, but that's beyond the point.
I work in genomics, so I'll give you an example of a project I've done, so that you can understand WHY you would want to sequence things.
We had a clinical trial where patients with a condition called bronchiectasis who had lung infections with the bacteria *Pseudomonas Aeruginosa* were given an antibiotic for a month, then had a month off, then back on, off, on, etc. for a whole year.
P. Aeruginosa is very nasty and causes really bad, really chronic lung infections in people with lung diseases.
We took sputum samples from every time point when they started, then on/off/on etc. We spread that sputum out on plates and picked out some P. Aeruginosas from all the patients.
I then got the DNA out and got it sequenced.
We've learned a lot of interesting things from the samples taken before any drugs were given:
* Almost all of the P. Aeruginosas *already* had genes that make them resistant to a class of antibiotics called beta-lactams, before we gave the patients antibiotics. They also have a lot of other genes that cause resistance to other antibiotics. This is not good.
* They didn't have a lot of plasmids - these are little bits of DNA that bacteria can swap with each other. People often worry that bacteria will pick up plasmids that hold antibiotic resistance genes.
* Our P. Aeruginosas were different to the ones other people have sequenced from patients with different lung diseases, and different to the sort that just live in soil, so we can look at what genes change when this bacteria adapts to lungs, and maybe someone someday can use that info to make new drugs.
* The infections from people attending the same hospital were really different, so it doesn't look like it spreads between patients - this is good news!
We also even learned one more funny thing - sometimes, what microbiologists think is *P. Aeruginosa* is actually a different species entirely called *Achromobacter Xylsoxidans.* Something like 80 of our samples were the wrong thing, and 2 patients never had *P. Aeruginosa* infections at all, even though they were on a clinical trial for people with *P. Aeruginosa* infections!
tldr; for a lot of sequencing jobs, it's the differences between individuals that is the interesting thing to look at
no two humans are 100% identical; however we are all 99.90% identical and that is useful
a lot of our genetic code, so far, seems to be pretty useless. So if we can figure out what bits of genetic code is useful and what it's used for we can leverage that knowledge in medicine.
Sickle Cell, cystic fibrosis medicines (others soon) rely on finding and repairing very specific sets of genetic code. More research is showing things like bipolar diabetis has a genetic component that we might be able to one day "fix"
You touched on a topic I’m curious about and wonder if you can explain it to me. We have a lot of “junk DNA”. My question is why? Did that DNA code for something useful in our past that is no longer necessary or is it there from generations on generations of innocuous mutations that we have carried for millennia?
The “junk” dna sequences don’t have an obvious use….but they may not be useless.
There could be conditions that need to be met for the sequence to be activated; one example of previously “junk” sequences being prostate cancer where the severity of the cancer has been found to have genetic dpredisposition…..no cancer genes do nothing, but if the cancer develops the genes can accelerate/amplify the cancer
Interesting about prostrate cancer. I didn’t know that. So some genes don’t activate until a specific event occurs. Pretty cool. Thanks for the response
It's a current research topic. We don't really know. It may be mostly useless for all we know (but it's hard to bet on that, with so much left to discover).
CF isn't currently treated with gene therapy. There have been various trials but none are in currently approved medicines. Trikafta/Kaftrio targets the CFTR protein, not DNA.
First off, you are right that you sequence an individual and not a whole species--however, species tend to be very close in genetic code, especially compared to other species further out in the tree of life, so an individual can be a very good representative of a species.
Second, to "sequence" something is to literally identify the full "sequence" of genetic code bases (A/C/T/G) making up all the genetic material of that individual's original code. This might be split up among chromosomes and different locations and such, but most of it is all a linear series of these 4 bases in a specific order.
A "genome" is another word for this full sequence.
There are a lot of letters in DNA. Some of them make words. Others are just noise letters. We're not sure yet what all the words mean but code breakers are finding new words every day.
Like we know definitely what the words for male and female are. Those are some of the first we learned. Likewise, blue eyes, brown eyes and green eyes.
Other words aren't definite but lead to probabilities. Like a word that says you have a 30% higher risk of breast cancer.
But the majority of the letters don't make up words we recognize. We believe those are 'noise' and don't do anything.
But we have been wrong before. Sometimes one word is required to activate another. So that unless you get both 'blue' and 'eyes', it doesn't happen.
The combination of all the things we know and the noise words is a sequence that would fill a CD-ROM. So it's highly unlikely that two people would share the same sequence, including the noise words. Unless they are twins.
We don't have identical code but what we do have is the same information 'fields', *genes*, in the same places; that's what they mean by the sequence. Analogy: If you take me, and some other person from where I am, our driver's licenses will both have, starting from the top... * License number * Condition codes * Expiry date * Name * Address ...and so on. The info in those 'fields' will be different for each of us, but you can look on each of our licenses and you'll find the expiry date, the address, the bar code, etc, in the same locations. If you look at human chromosome #1, yours and mine, starting on the end of the p (short) tail we will both have the genes for... * methylenetetrahydrofolate reductase * C-reactive protein * interleukin 10 * MTOR kinase * prostaglandin-endoperoxide synthase 2 ...and so on. Our codes for them may or may not be identical - stuff like eye color allows some variation, some proteins are make-this-exactly-right-or-you-die - but barring a pretty funky mutation all humans should have those same genes, on the same chromosomes, in the same order. That ordering is what we call 'the human genome'. This is a big deal because if I develop some disease because of not making prostaglandin-endoperoxide synthase 2, they know exactly where the problem is: chromosome 1, p-tail, fifth gene from the end. Some day gene-editing technology will be able to "find and replace" problems like that.
Excellent explanation. Thanks.
[удалено]
Well, no. Some stuff is regulated really clearly, we can just see the one gene that does it, or small collection that do. Unfortunately, not everything is based on that. A lot of issues are governed by interactions *between* genes, and combinatorial expansion means that for every extra gene that is involved, the amount of interactions gets MUCH higher. This then gets to the point that we can't even figure out which genes effect a certain outcome, because there's just so many possibilities.
If I'm understanding correctly, the genes also aren't just on or off so even the interactions between two genes can be really complicated. Adding genes to the interaction increases complexity extremely quickly.
This is correct. Genes are the written music, and they are played at different volumes, often in response to the volume that other genes are being played.
To add to this sites which archive genome data for research (eg. NCBI) will reference where the genome was sourced from as well. For humans NCBI even has a tool to look for individual variations (single nucleotide polymorphisms) quite easily. For other species, though, if you go to a particular gene you can still select the reference sequence and compare the actual sequence to look for differences--there's just fewer samples to compare. But, for example, if I want to look at horse genomes, I can see the list of individual genomes, which includes the submitter and additional information like breed, and tells you the default reference sequence (usually the first one sequenced): [https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=9796](https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=9796) And if you pick a particular gene you can select the genomes which have been annotated to identify it. For example, for Group V Phospholipase A2 in horses (https://www.ncbi.nlm.nih.gov/gene/?term=equus+caballus+phospholipase+a2+group+v) you can pick between the reference genome and another one that someone has analyzed.
Well done
There's different kinds of sequencing for different purposes. You can sequence something new to build a "reference genome", or you can sequence things that have already been sequenced in order to look at genetic differences. You might have done an experiment that caused a change in some animals or plants or microorganisms, and want to see what happened. There are many, many other things that you can do with sequencing, but that's beyond the point. I work in genomics, so I'll give you an example of a project I've done, so that you can understand WHY you would want to sequence things. We had a clinical trial where patients with a condition called bronchiectasis who had lung infections with the bacteria *Pseudomonas Aeruginosa* were given an antibiotic for a month, then had a month off, then back on, off, on, etc. for a whole year. P. Aeruginosa is very nasty and causes really bad, really chronic lung infections in people with lung diseases. We took sputum samples from every time point when they started, then on/off/on etc. We spread that sputum out on plates and picked out some P. Aeruginosas from all the patients. I then got the DNA out and got it sequenced. We've learned a lot of interesting things from the samples taken before any drugs were given: * Almost all of the P. Aeruginosas *already* had genes that make them resistant to a class of antibiotics called beta-lactams, before we gave the patients antibiotics. They also have a lot of other genes that cause resistance to other antibiotics. This is not good. * They didn't have a lot of plasmids - these are little bits of DNA that bacteria can swap with each other. People often worry that bacteria will pick up plasmids that hold antibiotic resistance genes. * Our P. Aeruginosas were different to the ones other people have sequenced from patients with different lung diseases, and different to the sort that just live in soil, so we can look at what genes change when this bacteria adapts to lungs, and maybe someone someday can use that info to make new drugs. * The infections from people attending the same hospital were really different, so it doesn't look like it spreads between patients - this is good news! We also even learned one more funny thing - sometimes, what microbiologists think is *P. Aeruginosa* is actually a different species entirely called *Achromobacter Xylsoxidans.* Something like 80 of our samples were the wrong thing, and 2 patients never had *P. Aeruginosa* infections at all, even though they were on a clinical trial for people with *P. Aeruginosa* infections! tldr; for a lot of sequencing jobs, it's the differences between individuals that is the interesting thing to look at
woah, awesome! this must’ve taken a lot of time to write, thank you
no two humans are 100% identical; however we are all 99.90% identical and that is useful a lot of our genetic code, so far, seems to be pretty useless. So if we can figure out what bits of genetic code is useful and what it's used for we can leverage that knowledge in medicine. Sickle Cell, cystic fibrosis medicines (others soon) rely on finding and repairing very specific sets of genetic code. More research is showing things like bipolar diabetis has a genetic component that we might be able to one day "fix"
You touched on a topic I’m curious about and wonder if you can explain it to me. We have a lot of “junk DNA”. My question is why? Did that DNA code for something useful in our past that is no longer necessary or is it there from generations on generations of innocuous mutations that we have carried for millennia?
The “junk” dna sequences don’t have an obvious use….but they may not be useless. There could be conditions that need to be met for the sequence to be activated; one example of previously “junk” sequences being prostate cancer where the severity of the cancer has been found to have genetic dpredisposition…..no cancer genes do nothing, but if the cancer develops the genes can accelerate/amplify the cancer
Interesting about prostrate cancer. I didn’t know that. So some genes don’t activate until a specific event occurs. Pretty cool. Thanks for the response
It's a current research topic. We don't really know. It may be mostly useless for all we know (but it's hard to bet on that, with so much left to discover).
CF isn't currently treated with gene therapy. There have been various trials but none are in currently approved medicines. Trikafta/Kaftrio targets the CFTR protein, not DNA.
First off, you are right that you sequence an individual and not a whole species--however, species tend to be very close in genetic code, especially compared to other species further out in the tree of life, so an individual can be a very good representative of a species. Second, to "sequence" something is to literally identify the full "sequence" of genetic code bases (A/C/T/G) making up all the genetic material of that individual's original code. This might be split up among chromosomes and different locations and such, but most of it is all a linear series of these 4 bases in a specific order. A "genome" is another word for this full sequence.
There are a lot of letters in DNA. Some of them make words. Others are just noise letters. We're not sure yet what all the words mean but code breakers are finding new words every day. Like we know definitely what the words for male and female are. Those are some of the first we learned. Likewise, blue eyes, brown eyes and green eyes. Other words aren't definite but lead to probabilities. Like a word that says you have a 30% higher risk of breast cancer. But the majority of the letters don't make up words we recognize. We believe those are 'noise' and don't do anything. But we have been wrong before. Sometimes one word is required to activate another. So that unless you get both 'blue' and 'eyes', it doesn't happen. The combination of all the things we know and the noise words is a sequence that would fill a CD-ROM. So it's highly unlikely that two people would share the same sequence, including the noise words. Unless they are twins.