Resource: Genetics CHAT transcript – Tuesday 3rd December 2019

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Moderator: To kick us off. As a challenge for you all, tell me one thing about Genetics you think I wont have heard about.

Reka – Industry geneticist: Did you know about ‘jumping genes’ (aka transposons), and how Barbara McClintock discovered them by studying colourful corn that had kernels of many different colours?

Eugene – Wellcome Sanger Research Fellow Did my PhD studying human transposons

Francesca – Wellcome Genome Campus Education Development Lead: @Eugene @Reka what is the function of a Transposon?

Nikolai – Plant geneticist: Transposons can be fab. Transposons offer a way for genomes to evolve by copying existing genes (fully or partially); these copies are then freed from evolutionary constraints and can obtain new functions (yay) or simply become a pseudogene (booh)

Reka: @Francesca Tough to say as far as I’m aware – they are remnants of viruses that have embedded themselves in our genomes. I believe one theory is that while sometimes they can insert themselves into a gene and wreak havoc, they also contribute to maintaining genetic diversity

Eugene: The function of themselves as a genomic parasite is to make more copies of themselves — i.e. to reproduce. But like @Nikolai and @Reka say they can be coopted to do cool stuff to the genome.

Francesca: @all Thanks, how are scientists using transposons in research? It might be nice to give teachers some examples

Moderator: I’m going to ask really basically here, is a transposon then just a section of the DNA?

Eugene: Yup it’s a piece of DNA that can move around the genome. They can be used for a bunch of stuff. Early genetics studies used them to randomly mutate the genome and observe organisms for “strange” phenotypes.

Nikolai: @Francesca Classic examples of using transposons in research is transposon tagging and enhancer traps, which ultimately helped to identify many genes in maize (the species where transposons were discovered in)

Francesca: @Nikolai so they flourescently labelled the genes to see how they moved around?

Nikolai: No fluorescent tagging; that is too high tech 🙂 Essentially, you “move” a transposon close to a gene. In most cases nothing will happen, but in some lines a phenotype change will occur. Standard forward genetics screens were then used to identify the DNA sequence that led to this change (i.e. a gene tagged by a tranposon)

Moderator: When we say early research, how far back are we talking? Manipulting the genome feels very recent…

Eugene: I want to say greater than 25 yrs ago but could be longer. We’ve been editing the genome for a long time! It’s just a lot easier now with CRISPR

Nikolai: Genome manipulation is old. Essentially all of domestication is a story of genome manipulation (cows, dogs, wheat, rice,etc). But our tools are now much better to do this.
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Francesca: @all Who uses CRISPR here?

Nikolai: *holds up hand*

Francesca: What do you use it or and how does it work?

Nikolai: I use CRISPR in my research to study the function of a gene. Specifically, I am looking at sequences within the gene that control how it is “expressed”, i.e. when and where it is switched on.

CRISPR/Cas9 is a combination of two elements: one acts as a homing device (i.e. it identifies a unique piece of DNA sequence within the genome) while the other is a set of molecular scissors. In this manner, you can cut DNA in a single unique place. This cut is repaired but sometimes errors occur. It is these errors that you look for, as these will change the function of a gene.

Francesca: What are peoples thoughts on the use of CRISPR to edit the twins in China?

Reka: Scientifically it’s super cool, ethically it’s super not cool. There have been few details about it, and the scientist who did it has been AWOL for some months – just today actually I read that bits of the publications he wrote [but which never got published] have been revealed today.

Nikolai: Editing those twins was unethical (parents were not aware of what was going on) and pretty pointless. The knowledge behind the gene and its effects on disease resistance is not great afaik.

Moderator: I heard it wasn’t really gene editing or something is that right… if so what was it?

Nikolai: At the moment CRISPR/Cas9 is not true genome editing, but simply a tool to delete short stretches of DNA. The twins were “treated” with a CRISPR/Cas9 approach, i.e. a chunk of DNA in a particular gene deleted. This is not true editing, as it can only work in one direction (no “undo” button). But you could couple a different tool to the homing device, e.g. a deaminase that essentially creates a G-A mutation (a single base pair mutation).

Moderator: So it was like an audio editing tool with only one function, delete, trash etc

Nikolai: Yes, only one function. But this field is moving on (at different pace in different species). Ultimately, we should be able to replace any sequence within a genome with any other sequene, i.e. repair faulty genes (cystic fibrosis).
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Moderator: Has anyone done any outreach or engagement work recently with schools? If so, what is it that students find interesting about you and your work? How do they connect with you?

Eugene:  I was actually at a school this past Friday talking with students/teachers about genetics. Interesting to hear their takes, they really find it fascinating that so many things have a genetic component.

Francesca: At the Campus we have a visits programmes where schools can come to us and an outreach programme where we can go out to schools. Students really enjoy finding out about the latest sequencing technology – the MinION , the portable DNA sequencer gets them very excited. We have actually taken it into schools and done live sequencing!

Moderator: Woah, what do you sequence? The teacher?

Eugene: XD That would be great!

Francesca: We took in a cleaned up sample of bacterial DNA and they were able to tell within 30 minutes what species it was. Very Cool!

Moderator: Fascinating that can be done in class. Ok, what’s a way to for teachers to give students that sort of wow moment about genetics, maybe with less tech 🙂

Francesca: One of my favourite activities is a really simple one – DNA extraction from fruit using households materials like washing up liquid, salt, water and Vodka (has to be really cold). We have a cute animation on yourgenome and instructions.

If teachers are worried about using Vodka, rubbing alcohol / Isopropynol works really well and doesn’t need to be cold.

Reka: I love that one, it’s also my go-to example 🙂

Francesca: We also have Investigate activity resources which looks at genetic variation such as bitter taste, smells, ear wax type etc. PTC strips are great, some people are so surprised when they can taste something and others can’t. We have also just worked with the BSA to create a set of CREST superstar awards for 7-11 year olds to get them thinking about DNA and the world around them.

Nikolai: A nice “low tech” example of genetics are the glass gem corn varieties; these maize lines produce cobs with colourful kernels. It was with these that Barbara McClintock discovered tranpsosons (can’t get rid of them tonight :))

Reka: Nope, they keep jumping right back into the conversation!
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Moderator: Change of track, did anyone see the documentary from BBC4 recently about eugenics, Science’s Greatest Scandal? Talk about eye opening. How much day to day do you get time to think about the ethics of your science?

Eugene: I’ve been thinking a lot about it lately, I work around the Genetics of Intelligence, and it is a very heated topic. I’ve been thinking a lot about how to properly communicate my science and make sure that what I am doing is well controlled and tested.

Nikolai: Haven’t seen that documentary (yet). I think the Kurzgesagt Youtube channel had a good video on Eugenics.

Reka: Kurzgesagt is a fantastic YouTube channel! Educational and gorgeously-drawn/animated. That could actually be a really nice resource for teachers too!

Francesca: They are good, may be a bit long for some students but completely agree they are FAB! @Eugene, tells us about the polygenic risk you have been working on its really interesting.

Eugene: So what we are trying to look at is how “risk” for developmental disorders may be inherited from parents via polygenic scores.

Moderator: @Eugene how would you use a polygenic score once you have one?

Eugene: Depends at the moment on which score. For psychological traits, it’s kind of a fun thing to see how it compares to my actual trait. For something that could be actionable, like my risk of prostate cancer, I would probably try to be healthier and go to increased screening. So it’s very variable on which “score” you are looking at.

Francesca: What is the simplest way to explain a polygenic score?

Eugene: I think the easiest way to explain is that each of us have pieces of our genome different from other people, and that those pieces can increase or decrease or risk of a certain trait. If we add all of these pieces up, we can get a score.

Moderator: Whats the score out of? Trying to picture it

Eugene: In terms of a scale of 1-100? It doesn’t really work like that. It’s like a bell curve.

Nikolai: Yes, variability!! Whatever your genetics, the environment has a key role and can modify or even override it. It’s both the saddest part of being a geneticist (booh, what happened to my mutant) and the most exciting (new functions!).

Eugene: Most people are at the average, and some people are at the extremes. And those people at the extremes have higher/lower risk

Reka: It’s usually calculated not just for one person but for a whole bunch of people – for example all 500,000 UK Biobank participants. You then look at the distribution of those people’s scores for a given trait/disease, and compare any ‘new’ people’s scores to these to see where they are on the scale.

Moderator: I wonder, is the using the word ‘risk’, err risky, in some contexts, cos of its negative connotations?

Eugene: Yeah, the field has started to move away from “Risk”. For things like height, its now just a polygenic score, but for medical stuff it can still be a polygenic risk score. Subtle, but important.

Moderator: Ok so this is something that might be used in clinical settings or is it already being used?

Eugene: Not quite yet. NHS is working on evaluating clinical utility. It is my opinion (and many others) that they will enter the clinic at some point in the future.
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Posted on December 5, 2019 by in Live chat highlights, News. 1 comment

One Response to Resource: Genetics CHAT transcript – Tuesday 3rd December 2019

  1. alenapance says:

    Genetic information is already used in the clinic, even is not perhaps as a general score. For example, people who come to the clinic with heart arrhythmias are checked for specific single nucleotide changes or polymorphisms (SNPs) that are associated with changes in the expression levels of specific ion channels in the heart that are at the origin of these disorders. The clinicians can then use the data base to contrast the mutations they find in their patients in order to confirm the diagnosis and also increase the knowledge and understanding of these conditions. They can also look at the family tree to study inheritance and compile the existing information to work out a prognosis for the patient.

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