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Down the Rabbit Hole: The Genetics of Speech and Language – Dianne Newbury, Senior Lecturer

Dr Dianne Newbury is a Senior Lecturer and Researcher at Oxford Brookes University, UK. Dianne’s research focusses on speech and language disorders and the role genetic plays. Her research team hope to determine what contributes to these problems in order to develop better ways to help children cope.

Please note the transcript has been edited for brevity and clarity.

FLG: Hello everyone and welcome to the latest Down the Rabbit Hole interview. Today, we are going to be talking to speech and language expert Dianne Newbury. So, before we begin, Dianne, if you could just introduce yourself and tell everyone a little about what you do.

Dianne: My name is Dianne Newbury, and I’m a Senior Lecturer and Researcher at Oxford Brookes University in the UK. My research is interested in genetic contributions to speech and language development.

FLG: What are developmental language disorders? Can you provide us with some examples of what these are and some of the symptoms that these patients have as well?

Dianne: We’re interested in genetic contributions to how people learn and develop and use speech and language. One way that we look at that is to look at children who have difficulties developing speech and language, with the idea that there might be something slightly different about them that can explain how everybody learns speech and language. So, the children who we look at have something called developmental language disorder or DLD. This is a relatively common disorder; it affects about 5% of children in the UK. But yet, very few people have heard of it, if you compare it with something like autism or dyslexia that people have heard of. Developmental language disorder people aren’t really heard of so much. I think that shows that it’s almost like a hidden thing.

All children go through different phases of speech and language development. So, children who have developmental language disorder might use speech and language in a way that you think is a bit young for their actual age. But that doesn’t necessarily trigger any bells. But then they also struggle understanding what is being said to them. And again, that can be a very hard thing to pick up, because they learn to compensate for that, and to follow things in a different way from how other children might in the classroom. So, it can be a really hard thing for someone to spot. But essentially, they have difficulty. They’ll use quite immature language, will struggle with putting together complex sentences, complex ideas, and expressing those, and that will continue throughout their life. So, it’s not just a childhood thing.

Then, they also have difficulty understanding complex instructions. I quite often think of it like when you learn a foreign language, and you have set phrases and set ways that you can say things and you go into a shop, and you ask for something, and you’re quite happy with that. And you can follow the conversation as long as someone sticks to the script. But if you then realise you need something and you don’t know the word for it, or someone deviates from that script that’s in your head, then the use of the language can get very hard very quickly. I always think that must be what it’s like for children with DLD. That as long as the language follows the script and follows the way that is at the level that they can cope with or are expecting, but as soon as something unexpected happens, it can be very hard for them, they can get very lost very quickly.

FLG: Is it something that’s quite hard to diagnose? Can it get missed?

Dianne: Most children will get diagnosed because their parents will be concerned about their language development and so they’ll get referred to a speech and language therapist. They tend to be the children who have these expressive problems with the language use. The ones that are really hidden are those children who have problems understanding language, because it is quite hidden away, and you can’t see what they’re thinking. So, that can be quite hard to diagnose.

The other problem with diagnosis is that the actual problems that the individual has will change throughout their life. So, at any one time point, there’s not like one thing that you can say, ‘Yes, that means you have developmental language disorder’. So, it can be very different from one child to the next child as the ways that we use language are very different. The way that you use language, and the way that I use language are going to be very different between us. Developmental language disorders are very different from one individual to the next. So, it can be really hard to spot and really hard to definitively say, ‘Yes, that is the issue’. And then even when you do get the diagnosis, that doesn’t explain why you might be having these difficulties because we don’t understand how individuals learn to use speech and language, and why some individuals might struggle with that more than others.

FLG: In general, why is studying speech and language so important, and how does that impact human health?

Dianne: I think it impacts everything we do. If you think you had to go through a whole day without saying anything, that would be a very difficult thing to do. Now, imagine that you couldn’t understand anything. And again, I use that foreign language analogy. If you’ve been abroad to a place where you just don’t know anything about the speech and language, you can see how difficult it is. So, I think it certainly impacts everyday life, it makes everything really hard because as we communicate, that’s an integral part of being human. And people just expect you to be able to follow what they’re saying. That’s the way that I transmit ideas from my head to your head. And if that’s a hard thing for you to follow, then it can make everyday life really hard.

And then it also impacts a lot on children’s education, and their educational attainment. Because so much of education is based upon speech and language. You can imagine if you’re sat in a classroom, where there’s lots of things going on, and you have to follow a teacher, and that’s hard for you to do anyway, with all those distractions and everything going on around you, it’d be very easy to get lost very, very quickly. So, it almost has like a compound effect throughout education.

FLG: In terms of DLD, what is our current understanding of this disorder in terms of its inheritance? Are there known single genes that are heavily involved? Or is it variation across loads of different genes?

Dianne: It’s quite hard to say, because as I said, it’s not like there’s a definitive, ‘This is DLD, and this is not’. But in the majority of cases, we think it follows what we call a complex inheritance pattern. So that means that there are many, many genes involved, and those genes together combine to confer your risk of DLD. Having said that, in genetics, we’re starting to understand that classifying disorders as complex or Mendelian, so single gene or multi gene, doesn’t always follow as we would expect. So, there are some cases of individuals and families where we see a single gene inheritance pattern that seems to be associated with quite striking speech and language deficits.

So, a really famous example of this is the KE family. And they have a mutation in a gene known as FOXP2, which is a transcription factor, so it switches other genes on and off. The mutation prevents the transcription factor from working and all the individuals who have that particular variant have very particular difficulties with language, especially with producing language. So, they have what we call orofacial dyspraxia, which means if you think about the movements that my lips and my tongue and my face are making in order to allow me to speak, that’s where the difficulties lie with those individuals. They have trouble with that motor control of the orofacial muscles.

FLG: What are some of the specific genomic tools that are being used to help investigate these disorders?

Dianne: So, because we think the majority of cases are complex disorders, we are applying approaches like genome-wide association studies (GWAS). So, we go, and we collect very large cohorts of children who are affected by speech and language disorders, and then look for common variations that are more common in those individuals than in individuals who don’t have speech and language difficulties. But this can be problematic in itself, because to assess someone’s speech and language ability is quite a hard thing to do. And takes a long time. So, I think the largest GWAS to date has been a couple of thousand individuals. And that really doesn’t give us the power that we need to identify the underlying genetic variants. So, there’s a big push in the field at the moment to think about how we can combine existing datasets and how we can ramp up those numbers. Because in other disorders, we see that an increase in sample size goes hand in hand with an increase in power.

FLG: How can more advanced tools like whole-genome sequencing provide deeper insights in terms of the potential role of non-coding variants in this disorder?

Dianne: Yeah, so as I said, we apply the genome-wide association because we conceptualise DLD as a complex disorder. A whole-genome sequencing approach can be really powerful if we think there are major gene effects. So, if there’s one or two genes that explain a large proportion of someone’s risk. And current research shows us that even within a complex disorder, there are likely to be individuals out there who are more at the monogenic end. And then there’s individuals who have really, really complex genetic reasons for their difficulties. So, we can try and identify those individuals who are more at the monogenic end. And we can use whole-genome sequencing approaches, which can help us to identify rare variations that contribute to the disorders. Then, once we know the genes, we can follow back, and then look at those in the more complex cases. And in that study design, we really focus upon still the coding variations. So, in those original families, when we’re doing whole-genome sequencing, we can see that there are really, really rare variations that are likely to have a big effect on the protein. And then we hypothesise that it explains a certain amount of risk within that individual. But that gene will also be important in a more complex model as well.

In terms of the non-coding variants, that’s almost like another step further. But that would be good to be able to do and I think as we start to understand the more monogenic effects and those major gene effects, then we can start to think about what the relationships between those genes are and start to look at things like non-coding differences between those individuals.

FLG: What have been some of the key findings so far and what are the key pathways that are involved?

Dianne: There has been a handful of genes that have been identified for DLD. It still doesn’t really lead us to the pathway level quite yet. One really big line of study has come from that case that I was talking about with the FOXP2 mutation. By looking at what genes does FOXP2 to regulate, we can then look at what that tells us something about the FOXP2 wider pathway and we see genes within that FOXP2 wider pathway definitely contribute to speech and language disorders that are not because of FOXP2 but are FOXP2 related.

Then, we also see pathways that we know are important in brain development and brain function. So, things like calcium pathways that control calcium levels have been shown to be important in speech and language development.

The other interesting thing that we can do once we start to understand a little bit more is to compare the genetic variations that contribute to developmental language disorder and how they overlap with other childhood disorders. We often find that families where DLD is quite common, also have individuals who are affected by things like dyslexia, ADHD, and this is all part of that complex genetic mechanism that I was talking about that. Variations that put you at a risk of DLD may also put you at risk of dyslexia, because there’s this underlying shared biological mechanism. And we do see that. We see that there are likely to be shared biological reasons for these disorders that overlap. Each of the disorders will also have a slightly unique and different thing that to them, but there is also this shared underlying component. So, by understanding that, it also helps us to draw links between spoken language, written language, and other behaviours more generally. So, it starts to help us to understand how we develop and use speech and language.

FLG: How has the role of the environment been explored in this area?

Dianne: In terms of DLD, yes. I think originally people assumed that children who were struggling to develop speech and language that it could be explained by their environment. But we know some environmental things that support children’s speech and language development. And we know some things that challenge children’s speech and language development. But it’s certainly not true that all children who have DLD are bought up in that challenging environment or there is anything environmental that completely explains DLD.

FLG: How can our findings about DLD be translated into the clinic? How can it also inform the educational system as well?

Dianne: Yeah, so I think this is different. When we think about genetics, we think, ‘Okay, we’ll find out what’s causing this disorder at a genetic level and then we’ll be able to diagnose individuals and we’ll be able to treat them’. But I think for more complex disorders, like developmental language disorder, because it’s so complicated it’s not thinking about diagnosing. It’s more thinking about if we can understand why these children are having difficulties in the first place – and the biological mechanisms can help us to start thinking about those things – then, we might be able to find out better ways to diagnose earlier. Not by genetic testing, but more because we understand what the early symptoms and signs are. And a better understand about how these overlap and what things we can do to support children who are having these difficulties. Because as I said, the environment can have a big impact in terms of support. We already know that speech and language therapists do a great job in guiding children. But if we can better understand why particular individuals are having difficulties, we can tailor treatment better. And we can also design educational programmes to help children and to provide support where they need it most.

FLG: Earlier you mentioned one of the challenges as being sample size. But what are some of the other challenges in this area?

Dianne: I think the main challenge is just how complicated it is. It’s complicated at the behavioural level, the neurological level and the genetic level. There are just so many things going on that just by looking at the genetics doesn’t really provide a whole picture. So, I think we have to take this holistic approach. And that can be really hard in terms of study design, thinking about how we account for all these different things going on simultaneously that are also changing over time. I think that’s why it’s really important that we work together with all the different specialists in all the different areas and really take this collaborative research approach for complex disorders. I think that’s really the key to generating translational research.

FLG: Some research has been done on the Robinson Crusoe Island. Why is this island so significant? What is some of the research being done there?

Dianne: For one of our studies, we work with a special population known as the Robinson Crusoe population. And they are called that because they live on the Robinson Crusoe Island, which is a tiny island off the coast of Chile in the middle of the Pacific Ocean. We’re particularly interested in the Robinson Crusoe population because there is a particularly high incidence of speech and language disorders. That was first noted by some speech and language therapists in Chile. This is a nice example actually of that multidisciplinary approach. They were interested in characterising and understanding how the environment had an impact on children speech and language development on the island. And then we saw their research said, ‘Actually, this would also be really interesting from a genetic point of view’. Because they live in this very isolated population, genetically, they’re known as a founder population. So genetically, it’s almost like a simplified genetic structure. So, by looking at the underlying genetics, and combining that with the information that the speech and language specialists were collecting, it gives us greater power to identify the underlying genetic variations.

So, we’ve done some genetic sequencing and genetic association on the islanders. And that enabled us to find this genetic variation that was much more common in the individuals who had speech and language disorders than the individuals who didn’t. Our research now is going on to look at what does that genetic variation do? And what might that tell us about speech and language development? So, it’s in a gene known as NFXL1, which is a transcription factor. We’ve got a research student in the department at the moment who’s looking at what genes does that transcription factor control? And what difference does that particular variation that we saw in the Robinson Crusoe population have upon that controlling pathway?

FLG: You’re also studying people who talk backwards. Why is studying these individuals so important? How can that inform us about speech and language as well?

Dianne: As I said, right at the beginning, I’m interested in how everybody learns to use speech and language. If you think about what we’re doing it is just absolutely amazing. A baby is born into this world, there’s all these noises and everything going on around them. It’s all foreign, this is new noise that they have not been exposed to before. And somehow out of that noise, the child is able to pick out speech and language and with no prior knowledge of that speech and language, they’re able to, in a relatively short timeframe, understand and interpret what’s being said to them, and express their own thoughts using the speech and language. If you think about what’s happening, it’s just amazing that they can do that.

So, one way to leverage research in that area is to look at the disorders. But another way is also to look at the other extreme of speech and language use. And so, we’ve been doing this with a group of individuals who are very good at manipulating speech. So, you can say a word to them, and they’ll immediately be able to reverse that word, and say it backwards. They’re called backward speakers. I can’t do this, but if you said to me, ‘Reverse the word lemonade’, I would say, ‘Eda….nom…el’. So, I’ve just reversed that word. But that wasn’t particularly impressive. If you talk to someone who can backward speak, and say to them, ‘Reverse that word’, they would have done it just like that, even if it was a word that they’ve not previously heard of and even if it was a much harder word than lemonade. And, in fact, the people who we are working with can reverse entire sentences. So, you can give them this long sentence and they’ll literally reverse it word by word online, just like that!

So, at a language level, these people are really good at manipulating phonemes. So, the phonemes are the speech sounds that make up words. And when you hear someone speaking, your brain is automatically translating entire words and streams of sound into these phonemes and mapping those sounds onto meanings in your brain. And we know that phoneme awareness is a really important thing in terms of language development. We know that children with dyslexia really struggle with mapping between speech sounds, or between the written words and speech sounds in their brain. And children with developmental language disorders also have similar problems. And these individuals are at the other end of the spectrum, where they just find it really, really easy. When we talk to the backward speakers, we say, ‘How did you learn this?’ And they say, ‘I could just do it, I just found that I could do it’. So, it’s not like it was something that they trained themselves to do. It’s just something that they find really easy.

So, the idea behind that research project is that the reasons why they find it easy, may be similar to the reasons why other people struggle, and maybe similar to the reasons why the majority of people in the middle don’t even think about it. So, if we can find genetic variations that contribute to their ability, it may help us to understand everybody else.

FLG: Can studying people who speak multiple languages also provide us with insights?

Dianne: Yes, I think that’s another really nice example of extreme ability that may help us to understand the more general things that underlie speech and language. There is actually a group in Holland who are looking at people who can speak multiple languages. They probably find that easy for different reasons from the backward speakers. I think there’s probably also lots of other examples of these extreme abilities that can tell us things about different aspects of speech and language.

So, we know that when learning a second language, you’re using different parts of your brain from your mother tongue, or your initial language. If you think about the way that we learn, say French or German at school, we think about that in a very different way from how we use English. So, there are different underlying pathways. But some people still find that really, really easy, whereas other people find it a lot harder. And that’s probably to do with those connections in the brain that are firing or not firing. So, I gave a really nice demonstration of how I can’t backward speak. I also find learning foreign languages quite challenging as well.

FLG: It’s really interesting. What are your hopes for the future? What do you see the future in this field looking like?

Dianne: I’d like to think that the research into the disorders is going to help raise awareness of developmental language disorders, so that more people will have heard about it and be aware of it. I also hope it helps us to understand why some children struggle and help us to change the way that we rely so much upon speech and language. So, I guess being aware that it may not be so easy for some people as others. I guess that’s the first step in helping those children. Then, the research more generally, just helping us to understand how we all have this amazing skill. I just find it fascinating that the majority of people use speech and language, and we don’t even think about what we’re doing. But when you stop and think about it, you’re like, ‘That’s pretty amazing’.

FLG: Thank you so much for speaking to me today, Dianne. This topic is so complex, but it’s also so interesting and also so important within society as well. So, thank you for sharing your insights.

Dianne: That’s great. Thank you for inviting me.