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.

You can't eradicate downs. It's a de novo mutation surely? It's not hereditary?

There's lots of de novo mutations and unless every single mum gets genetic screening and has a termination based on undesirable DNA.

Hardly likely as in Africa women still bleed to death in childbirth and are denied even the most basic life saving care.

We could made a cure for Ebola but Africans have no money to buy the life saving drugs.

Science like everything is driven by the company profits

I worked in medical research when I left uni. We was working on a pin prick blood test to be used in doctors surgeries. We couldn't get our results within the tight deviations so the company moth balled it waiting for the day someone else thought of the idea so we could sue them over the patent. Because in theroy that would make as much money. Then the company shut our research project down. That's when I left science which has always been my main love in love for a better paid job in a different industry. I would love to do my PhD and go back to working out of love and not to pay my bills. But bills needed paying at the time

murmuration I think it's that too. Once you do physical illnesses, then the natural progression is then mental illnesses, then you start to get into the grey area of what's just someone's personality and what needs to be 'cured'.

(assuming that sequencing could ever impact mental illnesses)

I was a scientist butbalsonmoved tonabdifferent industry due to the pay. I did science A levels and at university. Tbh I found the teachers pretty irrelevant. I found the subjects (biology and chemistry) fascinating from as soon as we started doing them, compared to other subjects, and there was just never any question of me doing anything else. I did physics more out of necessity as I had to do 3 sciences for medicine or science at uni and i knew id do one of them, never really considered anything else.

This is my field, it's absolutely fascinating. I find so much hope in it.

About 30 years ago I worked for a year in a medical research council laboratory and this was all in its infancy. It was an incredibly exciting time but all the sequencing was done by hand, painstakingly slowly.

Even so it was imagined that one day we would be able to cure genetic diseases like DMD and I worked on the genetic basis of Lupus Erythomatosus. Its incredibly exciting that we are nearly there and it will change the medical world.

I have one cautionary note. We still do not understand what vast amounts of the DNA in a human body cell actually does. All the DNA which was not actually a gene was called 'junk' DNA in my day but I do not and never believed it was junk. I am concerned that DNA modification may well lead to outcomes that are unexpected and very harmful.

Sorry was going to come back, but called away by a poorly ds.

Yes, pretty much what murmuration said. There is a huge difference to me - someone with Downs or Kleefstra or Angelmans or Fragile X or one of the many 1000s of genetic conditions where there is chromosomal change in all the cells (or some in mosaic cases) means that who that person is, their personality, outlook on life, everything is tied up inextricably with the syndrome which affects their chromosomes. Rather than changing a few pieces of a puzzle it would be like getting a whole new one with a different picture.

I am probably not explaining myself very well (lack of sleep!)

Just marking my place, off to work but great thread!

DNA is in cells obviously. In the nucleus.

In chromosomes. Which are really really long, (I think 2m each) therefore they are wrapped really tightly around balls known as histones. This can be seen with an electron microscope, not a light microscope.
DNA stands for deoxyribonucleic acid
It is made up of a phosphate group and deoxyribose backbone with nucleic acids attached (adenine, thymine, guanine, cytosine) the nucleic acids are attached in pairs in the middle of the two phosphate/deoxyribose backbones. The way they are orientated makes the ladder twist. I won't go into how they are paired because that takes ages to explain!
So that's what it looks like.

Nucleobase, not nucleic acid

I agree that school science isn't all that interesting. Although Biology gets a good work out from the off (cloning and genetic engineering in first year of GCSE), chemistry gets a hard time of it.

For first year it's much more "materials science" which is perfectly valid but not chemistry in the truest sense and puts a lot of people, especially girls sadly, off. They get in to atoms and bonding etc in second year Chem but a lot of what we teach has to be re-done at AS and A level as what they are told at GCSE isn't strictly true.

I wish the science curriculum would be rejigged a bit to allow us to do the really fascinating stuff in proper detail.

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?
Well, if we've not seen the particular change before (in the genome databases), we don't know if it is a rare polymorphism (not causing the disease) or if it is a mutation that causes the disease. The more genomes we have sequenced and published, the more accurately we can call polymorphism or mutation.

With whole genome sequencing, we are usually looking directly for changes. We don't usually use the data to construct haplotypes or generate locational information, which is what I think you're referring to (although you can use the data in this way).

You might like to have a quick read on haplotypes and traditional mapping. That's the process of determining which pieces of DNA are shared by affected patients (particularly those in the same family) and thus, likely to contain the disease-causing gene. You identify which pieces of DNA are shared by scoring polymorphisms (is this base an A or a G? is this repeat 3 or 4 long? etc) and comparing across patients and unaffected family members. If affected people within a family all share the same version of a piece of DNA sequence, and the unaffected family members don't have the same version of that piece of DNA, we can often make predictions about how likely it is that piece of DNA contains the problematic gene. We then have to look at the sequences of all the genes in that piece of DNA and try to work out what's likely to be normal variation and what might be problematic.

With whole genome sequencing, we go straight to the entire sequence of all the DNA. We don't need to identify a haplotype, although we may have one from previous mapping experiments and can therefore discard any changes we see on chrmosomes/in genomic regions that we know don't contain the gene.

DNA is in cells obviously. In the nucleus. In chromosomes. Which are really really long, (I think 2m each) therefore they are wrapped really tightly around balls known as histones.

That's amazing that the strands are that long.

For non-scientists: a 'polymorphism' is a normal and harmless change in DNA sequence. We all carry lots of them in every gene and our individual genomic combination is fairly unique, how we identify both criminals and fathers, and probably what makes you you (hair colour, eye flecks, the shape of your big toe etc)

So at a particular position in a gene, I may have the base A while others tends to have the base G. Me having A makes very little or no difference to the function or activity of the gene or its protein product, so we say that this base position is polymorphic. Poly = many, Morph = form/shape.

If I identify a previously unseen change in DNA in someone with a genetic disorder, I have to make a judgement about whether that change is possibly a rare polymorphism or has the potential to cause disease. The more genomes I can compare to, the easier I can work out what's 'normal'.

The DNA in your body could stretch between you and Pluto.

17 times.

With whole genome sequencing, we are usually looking directly for changes. We don't usually use the data to construct haplotypes or generate locational information, which is what I think you're referring to (although you can use the data in this way).

You might like to have a quick read on haplotypes and traditional mapping. That's the process of determining which pieces of DNA are shared by affected patients (particularly those in the same family) and thus, likely to contain the disease-causing gene. You identify which pieces of DNA are shared by scoring polymorphisms (is this base an A or a G? is this repeat 3 or 4 long? etc) and comparing across patients and unaffected family members. If affected people within a family all share the same version of a piece of DNA sequence, and the unaffected family members don't have the same version of that piece of DNA, we can often make predictions about how likely it is that piece of DNA contains the problematic gene. We then have to look at the sequences of all the genes in that piece of DNA and try to work out what's likely to be normal variation and what might be problematic.

With whole genome sequencing, we go straight to the entire sequence of all the DNA. We don't need to identify a haplotype, although we may have one from previous mapping experiments and can therefore discard any changes we see on chrmosomes/in genomic regions that we know don't contain the gene.

Thanks for the response!

Yes, haplotypes and linkage analysis is what we covered. I don't think we did anything on whole genome sequencing. The main techniques we covered were karyotyping/banding, Array CGH, FISH/paint probes, and sequencing - though I believe it was impressed on us that sequencing is only done once you've narrowed down a candidate sequence. Is this not true, then, because it's easier and cheaper to do than it was before? This was all in the context of a genetics clinic helping couples who were TTC - is whole genome sequencing still not generally used in that context (and is that then why we didn't hear much about it, perhaps)?

I'm on my second year of biology and am just studying cell biology at the moment, it's fascinating stuff and I love reading my books.

Agree with ethics, how far do we go before we're selective breeding? Mistakes in DNA replication are surprisingly few (on phone so can't scroll upwards to see you said about that)

The DNA in your body could stretch between you and Pluto.

17 times.

Crazy. And that all fits in a little human body. How thin these strands must be (and all the information contained) is just incomprehensible to me.

I'm more interested in epigenetics tbh - will reveal a lot about disease - but that's a whole other level of complexity.

There is a form of DS (translocation) which is sort of inherited (in that if you have a translocation involving chromosome 21 you're at much higher risk of having a child with DS).

Used to work in cytogenetics many moons ago. Sequencing (not that I did much) took ages & was complex. Now my old lab sends samples off to somewhere (Korea??? Did I make that up) & it comes back via the computer days later.