Dr Dianne Newbury, Wellcome Trust Centre for Human Genetics, Oxford
But now itís time to turn to the genetics of another developmental disorder - Specific Language Impairment, or SLI. Up to two children in every classroom of 5-year-olds may have this condition, meaning that they have difficulty developing their language skills. To discover more about SLI, and how genetic research is helping scientists to understand it better, I spoke to Dr Dianne Newbury at the Wellcome Trust Centre for Human Genetics in Oxford.
Dianne - So, specific language impairment is essentially just children who have problems developing and learning to use language for no apparent reason. So, they donít have problems in other developmental areas, but just have this very specific problem with learning to use language.
Kat - So, they donít have hearing problems, they donít have autism?
Dianne - No. So, speech and language problems are quite common in children who have other developmental problems, so like you say hearing problems, autism. But the children we look at donít have any of those associated problems. Their main clinical concern is their speech and language impairments. Some children just have a language delay and then they catch up. Generally, the children that we look at with SLI, they are always behind their peers in terms of language.
You can imagine, if you start school and youíve already got problems with language, thatís going to compound as you go through school because obviously, itís such an important factor in terms of educational attainment. But a lot of children learn to compensate for their problems so if you were talking to someone with SLI, you might not notice that they had SLI. But they report that they always have problems - they have to concentrate harder than other people when listening to language and when trying to construct sentences as well.
Kat - So, what gave you the first inklings that there might be something genetic to do with this kind of condition?
Dianne - So, when I first came and started working in Oxford, I was working on dyslexia which is kind of a similar condition, but with written language rather than spoken language. At that time, there had been very little work done on specific language impairment, but there is somebody in Oxford called Dorothy Bishop who had done a lot of work in families and with twins, and sheíd been looking at the way that SLI runs in families. So there seems that there's quite a strong kind of heritable link. So, if your parents had language problems, then you're more likely to have language problems yourselves. And if you look in twins who are genetically identical, so identical twins, if one of them is affected, the other probably has a much higher chance of being affected. So, that gives us quite a good indication that there's some genetic contribution involved in the disorder. Itís not kind of a mutation in a specific gene which causes the disorder, but instead weíre thinking about kind of normal genetic variations between individuals. They're what we call these Ďrisk variationsí which slightly increase your risk of having a language impairment, but there's many of them scattered right across the genome and the more of them you have, the higher your chances of developing a language impairment.
Kat - Sort of a mix and match approach.
Dianne - Yeah.
Kat - So, how do you go about tracking down some of these genes that are involved in the risk of this condition?
Dianne - So, because there's so many of them involved, and each one is likely to only have quite a small effect size, they're much harder to track down than the kind of mutations which we normally think of with genetic disorders. But we apply similar kind of techniques and what we do is we collect DNA from families who are affected by specific language impairment and we compare the DNA between siblings in the families. So, you can imagine that if a pair of siblings are affected by specific language impairment, then we can sample their genetic material and we can look for regions of chromosomes which they have both inherited the same copy of from their parents. And if we do that in one family with a pair of siblings then we can narrow it down to about 50% of the genome that might carry contributory factors. If we do that across hundreds and hundreds, and hundreds of families, we should be able to narrow it down further and further, and further.
Kat - So, what have you found so far? Are there any really good candidates youíve got?
Dianne - Using that technique, we manage to identify region on chromosome 16 and a region on chromosome 19 which we think might carry genes that contribute to language impairment. And then using another method called association, we manage to narrow it down from these chromosome regions to 2 particular genes on chromosome 16. And one is called ATP2C2Ö
Kat - CatchyÖ
Dianne - And the other one is called CMIP, so yeah, very catchy names.
Kat - Do you know anything about what these genes actually do in the body?
Dianne - So, ATP2C2, there's a little bit known about it and we know that itís a calcium transporter protein and so, what it does is it pumps calcium out of the cell for transport out of the cell, and thatís quite interesting because calcium regulation is known to be involved in memory kind of processes, to be quite important in neuronal processes. So, that might link somewhere back into why children have language impairment. The other gene, CMIP, there's less known about it, but we know itís involved in the scaffolding of the cells, making the shape of the cell. And that might be interesting in terms of when neurons project and connect to each other. It may be important in those kind of processes, but thatís a bit less clear for that gene.
Kat - So now that you found these genes and you're looking for more, what's the hope that this knowledge could actually maybe lead to better therapies for kids affected by this disorder?
Dianne - My hope would be that it will provide us with a better understanding of why certain children are at higher risk of language impairment because given that itís quite a common disorder, it affects 5% of the child population, but we really donít understand why these children have language disorder, the differences between different children Ė so SLI in one child might look very different from SLI in another child and we donít really understand the best way to categorise it or what the underlying problem is.
So, if we could understand what the kinds of proteins and biological processes that are involved in it, then maybe that would help us to have a better understanding of how to categorise it and how to help the children. So, for example, if we knew that some children had variations in ATP2C2, that for those particular children, memory was important then we could use some kind of memory enhancing training in those children, and that would then help hopefully with their language impairment.
Kat - That was Dianne Newbury from the Wellcome Trust Centre for Human Genetics. And if you want to find out more about SLI, search online for the RALLI Campaign - thatís R A L L I.