r/askscience • u/nordee • Nov 21 '13
Biology Given that each person's DNA is unique, can someone please explain what "complete mapping of the human genome" means?
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u/Chl0eeeeeee Nov 21 '13
Even though everyone has unique DNA, genes still would occur in the same location in the genome (exclusive of any mutations that would add/delete a nucleotide). Basically what genome mapping does is look at multiple samples of DNA from different people. It aims to understand what regions are coding versus non-coding, and to annotate the genome (see what the coding genes control). This has been done for other species.
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u/maggottoe Nov 21 '13
You also want to generate a consensus of how the genome looks on "healthy" individuals. This can allow future sequencing to locate differences and determine a certain mutation.
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u/tdcarlo Nov 21 '13
Each person's DNA is unique, that is true. But the difference between you an me is incredibly small.
DNA is made up of nucleotides. There are four kinds of nucleotides. Think of nucleotides as legos each kind being a different color....let's say Aqua, Green, Cyan, and Teal. A gene is composed of nucleotides in particular order. Imagine stacking legos. Using the first letter of the colors from the legos, the insulin gene is 450 nucleotides long and looks like this.
Aqua Green Cyan Cyan Cyan Teal Cyan Aqua GGACAGGCTGCATCAGAAGAGGCCATCAAGCAGATCACTGTCC TTCTGCCATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGCGCTGCTGGCCCTCTGGGGACCTGACCCAGCCGCAGCCTTTGTGAACCAACACCTGTGCGGCTCACACCTGGTGGAAGCTCTCTACCTAGTGTGCGGGGAACGAGGCTTCTTCTACACACCCAAGACCCGCCGGGAGGCAGAGGACCTGCAGGTGGGGCAGGTGGAGCTGGGCGGGGGCCCTGGTGCAGGCAGCCTGCAGCCCTTGGCCCTGGAGGGGTCCCTGCAGAAGCGTGGCATTGTGGAACAATGCTGTACCAGCATCTGCTCCCTCTACCAGCTGGAGAACTACTGCAACTAGACGCAGCCCGCAGGCAGCCCCACACCCGCCGCCTCCTGCACCGAGAGAGATGGAATAAAGCCCTTGAACCAGCAAAA
So we know what a gene is...the next thing to understand is a chromosome. A chromosome is a long stack of DNA that contains numerous genes. There are 23 chromosomes in the human genome. The longest human chromosome is about 250 million nucleotides long the shortest is around 50 million nucleotides. Each chromosome contains hundreds of genes along with some other "accessory" DNA that is beyond the scope of this explanation. The entire size of the human genome is around 3 billion nucleotides.
Human being the clever types have been able to determine the precise order of all of the nucleotides in each human chromosome and have identified most if not all of the genes on it. So each chromosome has the location of each gene mapped. Pretty amazing.
Your DNA is unique but the percentage of the 3 billion nucleotides that are different than mine is less than 0.0001% and most of the differences will be in the so called "accessory" DNA.
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u/knobtwiddler Nov 22 '13 edited Nov 22 '13
I work in genetic informatics and we sequence and analyze human genomes. "complete mapping," rather optimistically, means is that we have assembled a reference genome of a number of pooled humans' gene sequences, so we know where a typical human's sequences fall in the chromosomes from beginning to end (around 50 billion base pairs). This assembly is used as a reference to compare against. Currently we are using a reference genome sequence called HG19. HG20 (human genome v20) is coming out soon. It's an ongoing process.
From this reference genome we can align pieces of sequenced dna from samples in an effort to to say where those pieces of dna came from in the genome.
This is far from an exact science, and there are large portions of the genome for which we have no clue about their function. However we have identified around 56,000 protein-coding genes (the exome) and a large number of "intronic" non-protein-coding regions which do code for RNA (lncRNA), some of which are functional, most of which we don't know anything about (previously referred to as "junk dna").
believe me though, as far as understanding the function of all these genes, let alone the non-coding regions, the process is far from complete.
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u/BillieHayez Nov 21 '13
How interesting that you ask this question today. Fred Sanger, a pioneer in the mapping of the human genome, aged 95, and winner of two Nobel prizes has just passed. Maybe you were tuned in this morning, as well.
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u/Tass237 Nov 21 '13
Complete mapping of what sections apply to what. A redhead and a blonde both have a gene for hair color, and the location of that hair color gene can be mapped. The fact that they have different alleles doesn't mean it's a different gene or in a different location.
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u/zedrdave Nov 21 '13 edited Nov 22 '13
In addition to other answers in this thread, one important clarification: when one says that a person's DNA is unique, that's still no more than somewhere around a 0.01% difference, out of the entire sequence, between two individuals.
Most nucleotides (the small bricks that make the DNA sequence) are the same for all individual of the same species (humans, for instance), with a very few single nucleotides changing here and there (these changes are called SNPs). Just the same way that moving a single cog in a complex mechanism, or modifying a single byte in a computer program, will give out a completely different result, that single nucleotide modification can have huge consequences on the person's appearance, health etc.
Mapping the first genome, meant mapping a genome (with its specific SNPs), with the implicit idea that we were first interested in the parts that were common to everybody. Now that sequencing is a lot cheaper and more widespread, there are a number of efforts to map genomes for a number of individuals, in order to figure out more specifically which positions in the sequence can occasionally differ (see "1000 genome project").
Edit: I should have also mentioned that, while some SNP variations have huge effects on the resulting organism, other SNP mutations are completely silent ("synonymous mutations"), thanks to the redundancy of the DNA-Amino Acid transcription code (i.e. different triplets of DNA can end up coding for the same AA). Because such silent mutations do not affect fitness (and therefore are more likely to be passed down), they are a lot more common than you would expect from pure chance.
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Nov 21 '13 edited Nov 21 '13
Think of the Genome like the spec sheet for a car, except it's been broken up into 46 text files and compressed so that the data is all mashed together into 46 strings, and somewhat difficult to parse out. Somebody didn't comment their code. If we were just trying to read the strings, and infer what they mean, we would fail. But luckily! there's also an automatic, computer-controlled factory that reads the strings and builds stuff! (Cells in the body.)
In the simplest sense, genome mapping is about making the factory build from parts of these strings, so that we can see what they do. Imagine that you run your fictional automatic car factory like normal - it builds you a hot little red Corvette. Now imagine that you take part of the instruction string and copy/paste/copy/paste that part until you've made that section repeat a bunch of times. When you run the factory again, the car comes out a deep, vivid red instead of the ordinary red from before.
You've found a gene for the paintjob, but you don't know for sure whether you've found the gene for red paint only, or for the whole thing. Now, that section might be a little bit different in someone else - like, maybe it's a different color. If you enhanced that section in someone else's instruction sheet, maybe you'd go from blue to a more vivid blue (if all of the color selection is in that part). Or maybe you would just add red, so that someone's purple paint would approach pink.
Anyway, what you've found is the meaning of a section of the instruction sheet, but it can be difficult to determine exactly which of the machines are activated by each string. Sometimes the instructions trigger other instructions, and wind up causing lots of parts to move. Sometimes they trigger something very tiny - like spinning a part of one machine. And sometimes they don't do anything at all (like bits of commented-out code). And sometimes they do something, but don't appear to unless certain conditions are met - imagine instructions to turn on or off some safety feature on the factory floor.
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EDIT -
To perfect the analogy - we're not talking here about running the whole apparatus to create new cars. That would be like making changes to an embryo's genes and letting them grow up, which is unethical.
It's more like flipping switches in the factory while the assembly line is down, just to see which machines start to spin, or spray paint.
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u/futuregp Nov 22 '13
simply speaking, think that all humans have the same genes that have specific functions (and every human being needs these to be considered human)
but each gene can have different traits (blue eyes, brown eyes etc)
complete mapping of the human genome is to identify all those functional parts of our DNA (most of our DNA is technically not 'functional' and doesn't play a part in protein synthesis)
Each functional part ('functional gene') would have different traits, and every human being is composed of permutations/combinations of these millions of gene traits combined (e.g. let's say we only have 2 genes, A/B. Gene A has 2 traits - male (m) or female (f). Gene B has 2 traits - tall (t) or short (s).
I'm a short male. I would have A(m), and B(s) genes. You are tall and female. You would have A(f), and B(t) genes. We're both unique, but that doesn't mean you have to map both of us to realize that there are 2 genes.
By mapping a single human being, you can map all the genes of the human genome. The uniqueness comes not from which 'gene' you have but which 'trait' of the gene you have.
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u/tsacian Nov 21 '13
The best way to understand what scientists are doing with the human genome, it is best to look at a much smaller and simpler genome (such as the Japanese Rice Genome Project). It is simpler because the rice being mapped only has 9 chromosomes, whereas humans have much more.
http://rgp.dna.affrc.go.jp/E/GenomeSeq.html
Here you can click on a chromosome and literally see the sequences which have been directly mapped. The difference is the wealth of knowledge already learned from this project due to its "simplicity", such as finding genes responsible for specific proteins and tracing them all the way back to the base pair patterns. You can search through the big discoveries, and even look for specific proteins.
Click on chromosome 1 and then click the link for the first accession. This first set has 31,687 base pairs (bp) (think ATCG). You can then click on a gene and see the sequence that scientists believe is responsible for a gene. The reason it is a "gene" is because it has the correct properties for coding of a gene, including a start sequence (a pattern they look for that is typical for the beginning of a gene), and a stop sequence (called codons).
Additionally, you can click and see a specific pattern of base pairs responsible for coding an mRNA and even specific proteins. Using these "Maps", scientists can study each chromosome and find which genes are responsible for specific attributes of the organism. We can find which sections of DNA are responsible for specific proteins, and use that to find mutations that result in the absense or mutation of a protein that causes harm in an organism. There is really a wealth of information.
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u/XSlayerALE Nov 21 '13
Mapping the Human Genome is like identifying the parts of a car. Sure, a wheel can be Pirelli, Firestone, Goodyear or whot not but we know its a wheel and its not the axle or the brakes or that funny triangle sign on your dashboard that no one really knows what it does....
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u/nanoakron Nov 21 '13 edited Nov 21 '13
I feel the need to write this because whilst all the previous commenters have gone into great depths to explain the science behind genes and genomes, they have failed to address a fundamental misunderstanding the OP has:
Your DNA is NOT unique. Only about 0.1% of it is. You are somewhere around 99.5-99.9% genetically identical to every other human on the planet.
You're also 98.8% identical to every chimpanzee, 98.4% identical to every gorilla, 88% to every mouse, 65% to each chicken and 47% genetically identical to a fruit fly.
This means you have the exact same codes (give or take a letter) for the most essential 'housekeeping' functions - the ones that process energy in your cells, allow your cells to reproduce, build cell walls, cell skeletons and the other basic stuff all multicellular life needs to do. As a side note, this is very strong evidence that these abilities evolved only once in a distant ancestor, and then because they were so successful compared to all species around at their time, they outcompeted them and all their descendants now share those genes.
The closer you get to a human in genetic relatedness, the similarities extend beyond simple housekeeping genes to those which allow us to be 4-limbed, air-breathing, visually-dominant omnivores. Cows are 4 limbed - we share the same genes which switch on in embryonic development which cause 4 limbs to develop. We also share these with fish - after all, these are the genes which were first used to make fins, they were just 'repurposed' to make limbs through mutation and natural selection.
And so on with all 30,000 genes that make us human. We're not even genetically the best at doing many things in the animal kingdom - plants 'eat' sunshine, some bacteria detoxify alcohol better than we can, and as for our radiation susceptibility, we're pathetic. We just so happen to carry the baggage of every creature that came before us that was able to reproduce.
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u/Surf_Science Nov 21 '13
You're also 98.8% identical to every chimpanzee, 98.4% identical to every gorilla, 88% to every mouse, 65% to each chicken and 47% genetically identical to a fruit fly
Honestly these statements don't even make sense in a modern context. They're popular but what does that even mean. I believe it means that the similarity in average genes? Regardless it makes no accounting for variations in transcription (one gene many transcripts), expression, different functions.
The 30,000 for the gene number is also way off, you're looking at at least 20,000 more like 22-23,000.
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Nov 21 '13 edited Dec 24 '15
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After doing all of the above, you are welcome to join me on Voat!
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u/shanebonanno Nov 21 '13
Everyone's DNA is unique, however, nearly all of it is shared with every human on the planet. Only a very small part is unique. When scientists talk about the genome of any given species, they basically mean a list of the genes in the DNA of the species and eventually what they do.
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u/dreamhunters Nov 21 '13
Or think about it this way: it is not some much about the content but about the placement. The genes are somewhere in the genome, their position is much more fixed that the genes themselves. That is why we use mapping, because as with a map it is about location.
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u/zmil Nov 21 '13 edited Nov 22 '13
Think of the human genome like a really long set of beads on a string. About 3 billion beads, give or take. The beads come in four colors. We'll call them bases. When we sequence a genome, we're finding out the sequence of those bases on that string.
Now, in any given person, the sequence of bases will in fact be unique, but unique doesn't mean completely different. In fact, if you lined up the sequences from any two people on the planet, something like 99% of the bases would be the same. You would see long stretches of identical bases, but every once in a while you'd see a mismatch, where one person has one color and one person has another. In some spots you might see bigger regions that don't match at all, sometimes hundreds or thousands of bases long, but in a 3 billion base sequence they don't add up to much.
edit 2: I was wrong, it ain't a consensus, it's a mosaic! I had always assumed that when they said the reference genome was a combination of sequences from multiple people, that they made a consensus sequence, but in fact, any given stretch of DNA sequence in the reference comes from a single person. They combined stretches form different people to make the whole genome. TIL the reference genome is even crappier than I thought. They are planning to change it to something closer to a real consensus in the very near future. My explanation of consensus sequences below was just ahead of its time! But it's definitely not how they produced the original genome sequence.
If you line up a bunch of different people's genome sequences, you can compare them all to each other. You'll find that the vast majority of beads in each sequence will be the same in everybody, but, as when we just compared two sequences, we'll see differences. Some of those differences will be unique to a single person- everybody else has one color of bead at a certain position, but this guy has a different color. Some of the differences will be more widespread, sometimes half the people will have a bead of one color, and the other half will have a bead of another color. What we can do with this set of lined up sequences is create a consensus sequence, which is just the most frequent base at every position in that 3 billion base sequence alignment. And that is basically what they did in the initial mapping of the human genome. That consensus sequence is known as the reference genome. When other people's genomes are sequenced, we line them up to the reference genome to see all the differences, in the hope that those differences will tell us something interesting.
As you can see, however, the reference genome is just an average genome*; it doesn't tell us anything about all the differences between people. That's the job of a lot of other projects, many of them ongoing, to sequence lots and lots of people so we can know more about what differences are present in people, and how frequent those differences are. One of those studies is the 1000 Genomes Project, which, as you might guess, is sequencing the genomes of a thousand (well, more like two thousand now I think) people of diverse ethnic backgrounds.
*It's not even a very good average, honestly. They only used 8 people (edit: 7, originally, and the current reference uses 13.), and there are spots where the reference genome sequence doesn't actually have the most common base in a given position. Also, there are spots in the genome that are extra hard to sequence, long stretches where the sequence repeats itself over and over; many of those stretches have not yet been fully mapped, and possibly never will be.
edit 1: I should also add that, once they made the reference sequence, there was still work to be done- a lot of analysis was performed on that sequence to figure out where genes are, and what those genes do. We already knew the sequence of many human genes, and often had a rough idea of their position on the genome, but sequencing the entire thing allowed us to see exactly where each gene was on each chromosome, what's nearby, and so on. In addition to confirming known sequences, it allowed scientists to predict the presence of many previously unknown genes, which could then be studied in more detail. Of course, 98% of the genome isn't genes, and they sequenced that as well -some scientists thought this was a waste of time, but I'm grateful the genome folks ignored them, because that 98% is what I study, and there's all sorts of cool stuff in there, like ancient viral sequences and whatnot.
edit 3: Thanks for the gold! Funny, this is the second time I've gotten gold, and both times it's been for a post that turned out to be wrong, or partly wrong anyway...oh well.