h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

Entry: Genome Sequencing - A1068833
Author: Ste - U172039


Hopefully this can fill a glaring gap in the guide.



Ste

Some comments, more or less in random order:

"The most detailed level of genomic analysis is genome sequencing."

I would probably qualify this by adding "currently". If, X years from now, we can run an analysis that will spit out not only CGCTCTAGetc, but also what everything is coding for, I would consider that a higher level of detail.

Phylogenomics -- Another area that is comes into play in current research here, that you don't mention, involves the tracking of infectious diseases and their mutations. For example, with HIV, it is sometimes possible to track it through a population by tracking the mutations -- you can create these incredibly cool phylogenetic trees, but first you have to do sequencing on samples of the virus from the different people involved (and any one infected individual is probably carrying more than one 'strain', so it can get somewhat complicated). This involves very *short-term* evolution, but it's a retrovirus, so what do you expect?

"Humans differ by only two base pairs in 1,000, all variation between all people of all races are accounted by this difference. We are more similar to each other than we thought it seems." Grammatically, these sentences are somewhat confusing. Plus, I think some people might not realize that what you're stating is a proportion -- they might think the difference truly is *2 base pairs*. I might consider changing them to something like: "Humans differ by only 0.2% of their base pairs; this accounts for all the variations across humanity, regardless of race or ethnicity. We are more similiar to one another than we once thought."

I also think it might be worthwhile starting out at the beginning with some basic definitions regarding the differences between base pairs, genomes, genes, chromosomes -- many lay people I know confuse and intermix these terms quite a bit. I think the sentence "One can view a genome as a book, with chromosomes analogous to chapters, genes to paragraphs or sentences, codons to words, and bases to letters." is quite good -- I would perhaps emphasize that a bit -- perhaps put it in
the blockquote tag or in bold or somesuch. At the least, move it up to the beginning. And in that sentence, I would use "base pairs" rather than bases -- I would not assume that your readers realize that those terms are synonymous.

All in all, good work!


Mikey

Thanks for the comments Mikey


Regarding "The most detailed level of genomic analysis is genome sequencing.", I don't think that a genome sequence can become obsolete, that it can be resolved more in the future. It is the most fundamental, detailed level. From the sequence (and if it's in a gene) we can decode the CGA&Ts to see what amino acid it codes for, but it is a lower level of detail due to codon redundancy.


HIV? Hmm, It technically has a genome, but I think more what you're referring to is phylogenetics. Phylogenomics takes the trees one step further to infer gene function in unknown genes. Perhaps I should make this more clear?


"Humans differ by only 0.2% of their base pairs; this accounts for all the variations across humanity, regardless of race or ethnicity. We are more similiar to one another than we once thought."

This I like a lot. I'll pinch that, if you don't mind I replaced 'base pairs' with 'DNA' though, to simplify things.


Do you think I need more consistancy with my terminology. Do I need a glossary somewhere? I'll play around with putting the book analogy at the beginning, that's a very good suggestion, thanks.


Did you understand the sequencing part? That took me a good few revisions and it's never an easy thing to explain.

Also, how to I centre the CGATCGATCGATs? I tried putting it in a table (to keep it left justified, yet centred) and it went off to the right a bit. Any GuideML tricks I don't know of?



Ste

I've significantly redone the intro. Thanks Mikey.

Ste

Yes, I think I used the term phylogenetics in my post, didn't I? What I was getting at, is that it's another unique use of sequencing -- using it to track disease patterns and the movements of epidemics. I think in the future this is likely to become increasingly important, especially when you're dealing with transmission patterns where you can't depend on traditional field epidemiology of tracking contacts, etc. (Now, name each individual you passed by while spewing the SARS virus at the airport.....).

I don't know that I'd necessarily agree that it's a lower level of detail (back to the point of genomic sequencing, analysis, etc.) -- if you just know CCGATTACGGTA, that's one thing, but if you know that, and the enzyme it's coding for, you suddenly know primary, secondary, tertiary, and quarternary structure as well, not to mention the function of the enzyme itself. Even taking into account codon redundancy, I still think that's a higher level of detail than a string of letters.

I think a glossary might be a good idea, although if you had one, it would need to be at the beginning rather than at the end to be of much use to the average reader.

As far as getting the CGATTCT's to line up correctly, the only way I can think of to get that to work right is to make a table with two columns, no borders, and the underlined ones in the right column, and all the other letters in the left column.

Nice work!

Just a few things:

- Is it true to say that viruses have one chromosome? Many of them are RNA-based rather than DNA based, and the Influenza viruses, for example, have a genome of 7 RNA strands

- "A genome is defined as the entire genetic complement of an organism." If that's true, does the 'genome' include mitochondrial/chloroplast DNA? What about bacterial plasmids?

- In the table of organisms, it might be better to keep the common name (Latin name) order consistent ie, fruit fly (_Drosophila..._) etc.

- You use the term 'haploid' in a footnote, but it's probably worth providing a simple definition as well

- If you want to line up the 'terminated' nucleotides, you could use the tag http://www.bbc.co.uk/dna/h2g2/GuideML-PRE

- Your line on gene therapy suggests that retroviruses are the only way of doing it, but there are several others

- 'Exon' may require a little more explanation, but perhaps a non-geneticist needs to comment on that!

I hope you find some of that useful!

and, finally...

- "Genome sequencing technology... is a relatively simple procedure"

If I'd read that while I was doing my PhD, I may have said something very rude indeed

Lots of info to take in there, being a computer geek the closest I've come to biology/genetics is... well this! But I still understood it, I think!

One typo:
"this particular mosquito in the major ditributor of malaria, it even prefers to prey upon humans whom it can bite hundreds of time a day."

Should read:
"this particular mosquito is the major distributor of malaria, it even prefers to prey upon humans whom it can bite hundreds of time a day."

Pongo

Hi Mikey,

The thing with phylogenetics is that you don't need a genome to do it, nor does it predict anything about the function of genes in newly-sequenced genomes. There's this person at UC Irvine (where I'm off to do my PhD soon) whose job it is to predict the future adaptations of viruses like the 'flu using phylogenetics. It's amazing stuff, some of the trees she's come up with are huuuge. It's also dead wierd because this sort of stuff is used to figure out evolutionary *history*, not evolutionary future!

If you know the raw sequence, then you automatically know the primary, secondary, tertiary, and quaternary structures of any proteins that the DNA may code for. It's a given. Most of a genome does not code for proteins either.





Hi Danny, thanks for the comments

- Viruses and chromosomes, hm. I hate viruses, they mess up perfectly good naming conventions. I mean, they're not even alive. Ok, I'll change the footnote.

- ' If that's true, does the 'genome' include mitochondrial/chloroplast DNA? What about bacterial plasmids?'
You're right. It should be (looks it up) 'The total genetic content contained in a haploid set of chromosomes in eukaryotes, in a single chromosome in bacteria'. I've reworded it totally.

- In the table, sometimes the common name *is* the latin name! In those cases I've put it first, then given its alternative. I'll leave it like it is for now, but I'm open to persuasion.

- 'Describe haploid', i just removed the word! It wasn't really necessary to get the message across.

- Ah! I'll play around with the tag, thanks!

- Gene therapy - removed the retrovirus part.

- 'Exon'? That's an inhabitant of Exeter isn't it? Anyway, I've simplified it. Thanks.

- "Genome sequencing technology... is a relatively simple procedure"
Alright, I'll remove that bit. I was wondering if anyone would comment on it. Did you see my little link to the BBC 'DNA sequencing' description, it has pictures and everything!

Thanks Danny, dead useful stuff!





Ta for spotting the typo Pongo. I'm glad you understood it, 'cos that's the most important thing with an entry like this with a lot of meaningless jargon.


Thanks again everyone. I'm going to add a section where you can go to GenBank and tell people how to grab a bit of the human genome for themselves. It'll demonstrate that it's free, easily accessible, and anyone can do it from home.



Ste

Hello!!

I do like this entry, I don't think I could personally have understood it without some things I learnt in the first year of my degree, but that might have been me being hopelessly think! I'm glad Pongo could understand it! Personally, (as a scout!) I'd really really like some comments from some more non biologists to check that it's understandable.

The content seemed good though it's not really a topic I'm currently Au fait (if that's spelt right) with, and it made more sense to me than it did in my first year lecutres.

Hi Z,

Thanks for the comments. I too would like some more layman commentary. As that's the whole point; to make it understandable to everyone reading it.

What can I change to make it more understandable, do you think?

Ste

Well I'm a fourth year medical student, so I understood it all.

But I've just asked my friend who's a classics student, to read it, and he got it all apart from the bit on the mechanism of DNA sequencing.


What about, "To sequence DNA, you take a sample of the DNA you need to sequence, then unzip the bonds down the rungs of the ladder - using an enzyme. Then you mix the unzipped DNA with some bases, and also some "terminatore bases" which are flouresenctly marked. So imagine you have the sequence A C T

One strand might form where the first base A is a terminator base, so no more DNA forms. Another might form where A is a normal base and C is a terminator base, so a strand A C form. Yet another might form with A C and T as a terminator base.

As there are numerous strands of DNA then there will be strands that form of varying length. Using these strands then it is possible to work out the entire sequence of the DNA.

Thanks Z!

That's handy to know. Looking at it, that part does seem a little unclear. I'll redo it, taking on board your excellent suggestions.



Ste

Right then, I've altered the DNA sequencing part to make it more clear and added some colour in there for good measure.

Ste

Actually, I found the coloring distracting -- I think it was actually easier to read without it. Plus, I think chances are good it would be taken out during subediting, given the guidelines and all.

Good shot, though.

Heh

Yeah, I removed the colours. I checked it out in the non-goo skins and you couldn't see the yellow anyhow. Remember folks, if it ain't goo, it's poo.

Ste

This sentence: "Researchers have already identified nearly 200 genes in the Plasmodium genome that produce proteins that helps it to evade the body's defence mechanisms, and have also identified 276 genes in the mosquito genome that are critical to its sensory systems that helps it to identify its human prey."

is somewhat too long, or the first 'helps' should read 'help'.

'There has been many organisms sequenced to date' -> have
'Is it a boost to.. ' -> it is


Well, as well-written and comprehensive this entry is, it's still lacking something : balance. You're painting a nice and promising image. Now, what with the dangers (or call it 'risks') of gene manipulation, building Frankensteins, inventing the ultimately deadly bug, all the fuzz with GM foods?

Then, you might want to link to:
A885521 Gregor Mendel and the Basics of Genetics
A888780 How to Make a Genetically Modified Plant
A680050 Conservation Genetics

and perhaps some entries about related diseases:
A471296 Fabry disease
A616051 Hereditary Skin Cancer
A883523 Colour Blindness
A577046 Hunter Syndrome
A622432 Albinism
and so on.


Bossel

Hi Bossel, thanks for commenting,

"'Researchers have already identified nearly 200 genes...' is too long"

Agreed, I'll change it, thanks for spotting the typo too. Also added a footnote commenting on the sensory systems part.


Typos corrected


I see your point on the balance issue, though I disagree that stuff about the risks of GM foods should go in there. Genome sequencing is related to GE, but only as it's based in molecular biology. It would be like writing an entry on WW2 and putting in a section devoted to the recent Gulf war. They're both war, but the entry is about WW2, not the gulf war. GE is molecular biology, but the entry isn't about that, it's about one subsection of genomics, genome sequencing. It's quite specific really.

To address the balance issue, I waaaass thinking about adding a subsection to the 'Projects' part about the public vs corporate controversies that often come attached to these projects: Celera vs HGP; Syngenta vs IRGSP vs Beijing. It would be more relevant, and address the balance concerns. What do you think?


Oh, and thanks for the links, I'll try and squeeze them in somewhere.

Ste

I took a look at the introductory section and thought it wasn't in quite the right order and, for me at least, could do with some clarification and getting rid of one or two annoying bits. So this is what I've come up with so far, which might not be any improvement at all for all I know.

Bels

------------------


The genome of a cell or organism is the complete set of genes or genetic material present in it.

This genetic information is carried by the material called DNA. Each molecule of DNA consists of two strands coiled round each other to form a double helix, a structure like a spiral ladder.

Each rung of the ladder consists of a pair of chemical groups called bases (of which there are four types - A, C, G and Tadenine, cytosine, guanine, and thymine.</FOOTNOTE&gt. They combine in specific pairs so that the sequence on one strand of the double helix is complementary to that on the other: it is the specific sequence of bases which constitutes the genetic information.

If a genome was a book written in DNA, base pairs would be its letters. Codons (triplets of base pairs that code for one amino acid) would be its words, the genes would be its paragraphs, and its chapters would be the chromosomesChromosomes are threadlike linear strands of packaged DNA that reside in the nucleus of eukaryotic cells, or are single circular rings of DNA in bacteria..

Genome sequencing projects aim to work out the exact order of the base pairs (letters) in the DNA in all of the chromosomes (chapters) in an organism's genome (book). Once scientists have deciphered the letters of the book they can make sense of the whole genome, and obtain a solid understanding of the fundamental make-up of the organism that has been sequenced. Genome sequencing of an organism is the process of producing a detailed analysis of its complete genetic material.

This Entry describes:

what has happened so far in this relatively new field
how genomes are actually sequenced
why genomic information is useful.

In addition, some examples of notable genome sequencing projects are given.