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.

(Although I don't usually work in mouse)

Mice rock. I have vast respect for our little murine friends.

The ethics are interesting. I personally have no issue with altering DNA to reduce disease burden. I totally understand people's qualms but to me, removing condition X doesn't mean that people who are already born with condition X are worthless.. Everyone has value as a human being.
I suppose my only qualms are that we can't predict the future and sometimes something looks deleterious but is actually on balance beneficial. Being a carrier of the sickle cell gene is the classic example- they are more resistant to malaria and do have a survival advantage, and do the gene spreads.
I also think the media pushes this designer babies thing without explaining that most traits are down to a complex interplay between genes. Right now for example we can't even see exactly which genes make us tall, or smart. But we can potentially edit out single gene defects like cystic fibrosis.

Ds is about to go into the 100,000 genome study. He has been part of a study in Holland into a specific genetic condition, but his geneticist now thinks it might be something else.

I love listening to ds's geneticist talk about her field, she makes it just accessible enough for me. I heard her talking on Radio 4 the other day about macro/microcephaly and genetic changes in the brain - I want to read up on this, as she wants ds to have an MRI as he has macrocephaly amongst other genetic markers.

I would like to know what any of the knowledgable genetics geeks on here make of this organisation www.genespark.org/ - they post on a forum I am on, and caused quite a furore. They are obviously bloody good at fundraising. I can't, however, get my head around the idea of drug treatments for reversible Intellectual Disability (ID) disorders, specifically those arising from a gene mutation.

I work for a gene therapy company. We genetically engineer viruses so that they will inject a therapeutic gene into the host cell - the type of virus we use actually then puts the gene right into the host cell genome.

I have worked in this field for 15 years and still think it's really cool

Even cooler, you can use HIV for this (highly attenuated obviously!).

This can be quite interesting if you want to get a grasp of some of the basics.

knobblyknee missed that post - yes that's really cool. I do love the
Certain sources of DNA should not be used, such as: Your family pet

Just in case you were tempted

hazeyjane we are waiting to see a geneticist to be entered into the 100,000 genome study. DD has a PNKP gene defect which may or may not have caused her to develop West syndrome. At the moment there is no cure for the children with various different gene defects resulting in epilepsy and development delay, but maybe one day soon there will be.

I don't have an ethical issue with the altering DNA either, not when it's to help people and mean that diseases or conditions that make people's life more difficult can be eliminated.

But I do appreciate that the further we get with this, eventually there will become a point were we get close to the line. And where that line is for me is altering physical characteristics that aren't illness related, and that will be a grey area I think, one person's defect is another's interesting quirk, I guess.

By magnifying a human cell you would see the chromosomes - which are collections of lots of DNA.

Only in metaphase - right? They're not 'chromosomes' as such outside of that, right? Just a mess of chromatin?

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.

Are you saying you breed knockout mice? We were introduced to the concept but the suggestion was that there's just this place in the US that you order a tailor-made batch from. I love this stuff.

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.

To check my understanding (had a Medical Genetics exam this morning!), the differences you look for would initially be DNA polymorphisms, right? So not the things that might cause disease as such, but things that might be linked to a gene with a mutation in/near it?

My dss has cystic fibrosis and its very exciting to think they might be able to eradicate it. Even better if they might be able to come up with a cure for people aready here who have it. I was tested for the cf gene and it was negative. Had the result been positive, whatever I could do about ti, I know I couldnt knowingly bring a child into this world who had cf. As far as I know I would have been offered selective ivf. Nobody should have to suffer this horrible condition if it can be helped.

Oooh Miranda Bailey used deactivated HIV to cure some random disease or other that she 'discovered' in her genome lab.

On Grey's Anatomy.

Here endeth everything I know about genomes. And things.

As you were.

This is exactly why I started my health sciences degree with the open university. I get excited every time I open a book, which is good since its damn expensive and I study only for fun.

Absolutely agree, it's fascinating and incredibly exciting (non-science background here).

another geneticist here!

smillas - you're absolutely right that we visualise chromosomes when they're condensed in metaphase, but even outside of metaphase, it is becoming increasingly clear that what we thought was a big, messy tangle of chromosomes in the interphase nucleus actually has some underlying 3D structure. It's really early days but these 'chromatin domains' seem to have some sort of functional relationship with gene expression patterns. Great stuff

This thread is fascinating!

Thank you all you clever scientists for making it easy for thickies like me to understand it

I'm a HCP and the concept that we could eliminate certain diseases at a genetic level is just mindblowing.

Translation of the above for non-scientists:

When our cells divide the DNA in each chromosome becomes really densely packed so that the chromosomes are easy to separate when the cell splits in two. These are what we call 'metaphase' chromosomes, and look like the stripy Xs you might be familiar with. Clinical genetics labs use chromosomes in this state to diagnose genetic diseases that are caused by big changes in the chromosomes, like big deletions or duplications.

When cells aren't dividing they are in what we call 'interphase'. In this state the DNA is much looser and 'stringy' as this allows the code to be read to make the proteins the cell needs. We used to assume that in this state the DNA was shoved into the nucleus any-old-how, but new techniques are showing that there is actually some kind of underlying structure that we don't understand too well one pattern seems to be that genes that aren't needed by that particular cell (e.g. liver genes in a heart cell) live in the same neighbourhood in the nucleus, even if they are on different chromosomes. We have very little idea of how this works, but it would be really useful to know as we look for ways of turning genes on and off.

CalliopeTorres

CalliopeTorres

The aspect of 'eradicating conditions' I find difficult - there are conditions like cystic fibrosis, mitochondrial disorders etc that I can 100% see the reason for wanting to eradicate, but when people talk about eradicating something like Downs Syndrome, I think we are stepping into very dangerous territory.

Why, hazeyjane? What's the difference, to your mind?

Hi smilla- our technicians 'made' the mice and we then bred them to get various combinations of the inducer gene and the targeted gene. So one strain had the inducer linked to a gene only active in breast tissue for example. When you induce the little molecular scissors it only knocks the gene out in breast tissue.

And then you can go one stage further ... There was a mouse strain I worked on that had a naturally occurring mutation identical to a very nasty one in humans that causes multiple aggressive gut cancers very young. What you can then do is say 'right, if I knock out my gene X in the guts of these mice, does that make it better or worse?'
We found several genes that made it a lot better and these are now being investigated as targets for drugs to help people with the genetic disorder.
Right now we can only do this work in actual live animals. In the future I hope it'll be possible to do it all in silico (I.e, virtually.)
I was very fond of the mice. Amazing things...

Hazey, I understand what you're saying - it's the idea that being able to eradicate downs would devalue the people who currently have it? That it's not 'a disease'? My own personal opinion is that you can wish to stop someone else having a condition and still love and value those who live with it. I agree that these are all issues we need to debate.

I also wonder if it's a bit about conditions that influence someone's personality. If you cure cystic fibrosis or sickle cell anemia or type I diabetes or something, it's basically the same person just without a disease. Other than the effect dealing with having a health problem has had on their personality, it really shouldn't make a big difference. If you were to somehow remove someone with Downs' extra chromosome, a lot fundemental about them would change. They wouldn't interact with the world in the same way. It gets even fuzzier of you think things like autism, particularly milder versions - how much of what someone's 'personality' or 'who they are' is, is actually related to autistic features? Would my friend - only diagnosed last summer with high-functioning autism - still be the same quirky, geeky guy that I like if he didn't have any autism at all? How much of my own personality is due to schizotypical traits that I inherited from my schizophrenic mother, that had they been fixed in her I wouldn't have?

I get the devaluing argument too, but I wonder if the above isn't also something people feel.

Another scientist from the field of genetics here.
I work for a pharmaceutical company that focuses on treating patients with rare diseases. We are very passionate and dedicated to this work. Not all pharma is bad!