to not understand it, but be really excited by genome/DNA sequencing?

[AyeAmarok]

I've probably not even called it the right thing!

But over the last few months I have heard on the news so many breakthroughs. By finding the 'fault' in their genome and repairing it.

One was for a hereditary eye condition that caused blindness being resolved.

One was the 3yo girl with leukemia.

One the other day about recurrent miscarriage (if they allow the editing of embryos).

Someone just mentioned on a thread about personalised assessments of what illnesses you are most at risk of and how to mitigate against them.

I really feel that the research into this is starting to get somewhere, and we're gaining momentum and we'll start seeing breakthroughs more and more frequently. Like we're really on the cusp of something amazing.

I don't even really know what DNA is in the physical sense - it's always portrayed as that twisted ladder, if you magnify a single cell enough, is that what you see?

Disclaimer: Not a scientist. My terminology is probably all wrong.

It would be impossible to grow back a chromosome, sorry.

£125 is much too cheap, that test really won't tell you very much about yourself. Proper sequencing costs a lot more than that for a small area of genome, although next generation sequencing will make it a lot more affordable and accessible.

This was 20 years ago and a different life time. I wonder if that technique is now used - or are there quicker ways to identify an infection

You can chuck the sample into a mass spectrometer now and compare the peptide profile against known pathogens. Very quick. Or combine PCR with mass spec to identify DNA sequences, again against a database of pathogen references.

If you have a disease that runs in the family you could gene edit at the embryo stage and the new altered DNA would appear in subsequent cells as the embryo cells divide. For pre existing conditions viruses can introduce the edited DNA into affected cells.
DNA really is amazing.
There are 100s of enzymes that build and check each new DNA strand created.
DNA is a series of instructions to build proteins for our bodies (hair, skin, nails, hormones, enzymes, tendons, ligaments etc).
Everyone's DNA sequence is unique to them so we all have different proteins and are all different.
Every now and then DNA gets it wrong.
Editing allows us to make it right.
Very exciting.

Ego The aim is to compile a database of 100,000 genomes from patients with rare diseases (our unit) and cancer (other units) and controls (i.e. family members), to create a tool to study disease .v. gene sequence.

If I sequence the entire genome of Patient 1 with a very rare disorder, I will find 2000 interesting/rare DNA differences which could plausibly cause the disease. If I sequence the entire genome of Patient 2 with the same rare disorder, I again find 2000 interesting/rare DNA differences which could plausibly cause the disease.

Comparing Patient 1 differences with Patient 2 differences might mean that I can see they share only 100 of those interesting/rare DNA differences. Given that they share a rare disease, this allows me to narrow down the likely candidates in my hunt for which gene mutation is causing the disorder.

Now add Patient 3....

Immensely powerful tool, particularly for rare diseases where patients are often spread across different hospitals/trusts. Researchers need to be able to access genetic data, cross compare with their own data, work out what's "normal" and what might cause disease. It's tough with a few samples - people have spent years on single patients (and the entire project won't be that useful in diagnosing singletons), but with multiples, it (hopefully) becomes very easy.

Gene editing at the embryo stage. This is where ethics comes in
Agree. I suspect that the general consensus at the moment would be that this is unacceptable. The people that are going to opt for it (presumably those worried about very severe disease in their children) currently have the option of IVF/PGD and this would be more acceptable from an ethical POV, and technically easier (screen out, rather than screen and correct).

And I left all that to become a teacher
You teach biology/chemistry? How old when you made the switch to teaching? (if that's not too rude.....)

Like maidofstars I'm a genetics PhD.

It is absolutely mind blowingly interesting stuff. I worked on genetic mechanisms of development and cancer- basically finding out how things worked in normal development and went wrong in cancer and developmental conditions.

It's fascinating- you start off with one cell and build an entire, self replicating organism.

Sequencing is getting so much cheaper and faster and the technology we have to analyse the data is coming on leaps and bounds.

Tools like CRISPR (which I think is what the op has read about) are the way forward. We are effectively using proteins as tiny little cut and paste machines. That combined with nanotech and network analysis is the future. Exciting Times!

And may I say, op, how nice it is to hear non scientists get excited about these things? There's such a current of scientist bashing in the media (all talk of boffins/mad scientists) and a depressing current of anti- intellectualism too.

Skipton I have made a model of a congenital nerve defect using CRISPR and I'm about to start trying to correct it...

MaidOfStars that is so interesting. It really does make it sound like it's so close when you think of how adding in each patient with the same disease narrows it down.

Thanks for your explanation, I've read your first post a few times

There's such a current of scientist bashing in the media (all talk of boffins/mad scientists) and a depressing current of anti- intellectualism too.

Really? That's awful.

Out of interest, is the UK fairly 'up there' with this technology and research? I don't think a big enough deal is made about it here to encourage more people into it. (or I might just not be reading in the right places).

Oooh, really? Which one?

I used to use conditional knockouts (cre-lox) and it took forever to breed the models.., CRISPR is amazing!

To explain for everyone else..,

I had a system where you can 'knock out' the function of a gene, in any specific tissue, at any time. Why would you want to do that? You ask.,,

Well.. If you're making a mouse model of a disease and you know gene X causes it, you make a mouse that doesn't have gene X and see what happens.
But a lot of genes are essential for development, so often what you get is a mouse that doesn't get past the 'ball of cells' stage of being an embryo.
The system we used was effectively a little pair of molecular scissors - you could make the scissors work in a specific tissue to cut the gene out, so you can get s healthy adult mouse and say 'right, what happens if we stop this gene working in the breast tissue?' Or brain or gut or whatever. Pretty cool stuff, but CRISPR is even better as you can edit the gene, not just knock it out.,,

The U.K. Punches well above its weight, yes.

You know that thing that the DCs do at Christmas, that sort of wide-eyed teeth clenched thing of just pure excitement; that's what I'm like reading this thread!

I run genetics workshops with kids.

Put 100ml methylated spirits in freezer.
Mix 5g washing up liquid, 2g table salt, 100ml water, do it slowly so no bubbles until the salt has dissolved.
Mash up a kiwi fruit and add the washing up liquid mixture. If you can, mash it some more. Put the gloop in a jam jar/something screw top.
Float it in a basin of boiled water for ten mins.
Filter the lumps out.
Slowly add the ice cold meths down the side of the jar, so that this alcohol layer floats on the kiwi mixture.

You'll see a white layer appear between the kiwi gloop and the alcohol. Use a skewer to dip in to it and start spooling it out.

This white stuff is kiwi DNA!

My son has asd very probably due to a genetic duplication. But the gene in question is used in the embryo stage to lay down brain tissue. So even if you could cut out the 25,000 extra bits, it's already done its job wrong ( the blueprint to build a brain). But it's still very interesting. It opens up ethics like if my boys do have kids, would the boys test to screen this out? Would they want to? If yes then basically are they thinking they would want a child like themselves?

It's more than just the science. It's a lot of bigger questions too. Very interesting

This is my job and I have been involved in some of the work being reported in the media. Any particular questions, just ask, but I am off out tonight so may not reply instantly.

Some of my colleagues work with pathogen genomics to identify patient zero in hospital infections. Sequencing is so quick and easy now that you can do this in real time.

The UK is seriously good at this kind of thing and Genomics England are really revolutionising healthcare.

Have spent the afternoon designing our most recent Cre knockout scheme. Snooze.

And we already have the £1000 genone, it's just that the bioinformatics to analyse it properly will set you back £100,000