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SPECIFIC LANGUAGE IMPAIRMENT (SLI) RESEARCH TEAM - MAIN PAGE    

1. News

Recent news:

 

NEW Publication: 6th November 2008: Genetic study provides insight into language development A new study published by the Monaco Specific Language Impairment (SLI) team finds that a gene called CNTNAP2 is associated with SLI. The study found that certain genetic variants of this gene are associated with significantly reduced performance on a language test, 'nonsense-word repetition task'. In this test, individuals are required to repeat nonsensical words of increasing complexity. Performance on the nonsense word repetition task is related to phonological short-term memory span, and acts as a good behavioural marker for heritable SLI. This is the first time that a specific gene has been linked to ability on language-related tasks in SLI families. Interestingly, other groups have also found that certain genetic variants in CNTNAP2 are more common in people with autism than in the general population. This may indicate that genetic variants in CNTNAP2 may be involved in susceptibility to both SLI and autism. This would indicate that there is a shared genetic link between these two highly related disorders. MORE HERE See also: Oxford University press release Wellcome Trust press article See Editorial in New England Journal of Medicine: The Genetics of Speech and Language Impairments See also original article in New England Journal of Medicine: [Free to download pdf] A functional genetic link between distinct developmental language disorder [Abstract only] A functional genetic link between distinct developmental language disorder Media coverage: Times article (06.11.08): Scientists pinpoint gene behind language disorder Financial Times article (07.11.08) Breakthrough on language disorder See also: Link to webpage of Dr Simon Fisher

 

NEW Project: July 2008: The Monaco Group SLI and Dyslexia teams have received a grant from the Medical Research Council (MRC) for a new two-year project: "Gene-gene and gene-environment interactions underlying speech, language and reading development"

NEW! 25th October 2008 Times article cites Prof. Monaco "Spelling bee: Bad at spelling? Could be your genes"

2nd September 2008: SLIC 2008 Conference (Oxford): “Genes and specific language impairment: New directions” . See SLIC2008 Meeting Summary.
Access Conference presentations HERE
 

November 2007. Publication: Genetic and phenotypic effects of phonological short-term memory and grammatical morphology in specific language impairment [Abstract in Genes, brain, and behavior]

March 2007. Publication: New multivariate linkage analysis supports the importance of genes SLI1 and SLI2 MORE HERE

Newsletters:

• MONACO GROUP NEWSLETTER: MONACO GROUP 2007 NEWSLETTER

2. People

 

SLI RESEARCH TEAM
Laura Addis	laura.addis@well.ox.ac.uk
Dianne Newbury	dianne@well.ox.ac.uk

3. Overview

What is SLI?

Specific Language Impairment (SLI) is defined as a disorder in the development of language, despite adequate intelligence and opportunity and in the absence of any associated disorders that may underlie the language difficulties, such as hearing loss, autism or mental retardation.

SLI includes the following two disorders: Expressive Language Disorder and Receptive Language Disorder (ICD-10 classification).

It is estimated that SLI affects between 2 and 5% of pre-school children in the UK today, with approximately twice as many boys being affected as girls (the cause of this sex bias remains unknown). The language difficulties encountered by these children can have a major influence on their cognitive, emotional and social development. Whilst much is known as to the nature of the disability, little is known about its cause and neurological basis.  

Is SLI  genetic?

We know that SLI runs in families because you tell us it does. Studies show that a brother or sister of someone who has already been diagnosed with SLI will have an increased risk of developing the disorder themselves. There are two possible situations which may explain this observation: (1) something in the family environment (i.e. something in the way in which children are brought up) causes SLI; or (2) SLI is genetic and is therefore caused by the genes passed on from parents to children.

We think that the second theory is the closer to the truth. We know that some things run in families but are not caused by genes. For example political preference and which football team you support. These things are affected by the experiences a child goes through and the way in which they are brought up. However, in the case of SLI we often see that whilst one child in a family is affected his brother or sister is not, even though they were brought up in exactly the same way. In addition there seems to be no relationship between SLI and the level of language tuition given to a child or to the social or economic class of a family. This would seem to indicate that the environment alone cannot be causing language impairments.

One way in which we are able to distinguish between environmental and genetic effects is to look at twins. Identical twins come from a single egg and so have identical genes. Non identical twins come from two eggs and so share only half their genes. Therefore if genes are important in language development then identical twins should resemble each other more closely than non-identical twins with respect to language skills. Studies show that this is the case. In identical twin pairs, if one twin is affected with SLI then the other is about 90% likely to be affected. For non-identical twin pairs, if one twin is affected the other is only about 50% likely to also be affected.

What are our goals?

Although there is strong evidence for the role of a genetic component in SLI, we do not know which genes cause SLI or how the inheritance of language problems work. Working closely with other collaborators active in this field, we aim to track down the specific genes that may make some people more susceptible to language problems, and contribute to a better understanding of the genetics of SLI.

The results of our studies have been published in a number of scientific papers.

4. Research

4.1 The genetics of SLI

Specific Language Impairment (SLI) [OMIM 606711] is a complex genetic disorder. Complex disorders are caused by interactions between many genes, spread across different chromosomes.

(For non-scientists: more here on complex disorders).

The genes of each individual are slightly different and it is this variation that determines what you will look like and, to a certain extent, your chances of developing common illnesses such as heart disease. We think that some of these normal gene variations cause people to be more prone to language problems: the more of these susceptibility variants you carry, the more likely you are to develop SLI. This means that the exact combination of genes that are causing SLI may vary between different people. It also means that, in some cases, people who have a copy of some SLI susceptibility genes will still not develop SLI. This makes the detection of genes more difficult than it is for a simple (single-gene) disorder.

Over the past 15 years or so, there has been remarkable success tracking down genes for single-gene disorders such as cystic fibrosis, Duchenne muscular dystrophy and Huntington’s disease. But the approaches used for single-gene disorders are not usually powerful enough for complex genetic disorders, such as SLI or autism. Recently, however, novel strategies have been developed that are more appropriate for finding genes influencing complex disorders. We have used these techniques in our research, with the aim to identify the specific genes implicated in SLI.

(For non-scientists: more here on strategies for finding genes influencing single-gene disorders)

4.2 Initial studies

We know that Specific Language Impairment (SLI) runs in families and that this is partly due to genes passed on from parents to children. But as we do not know what causes SLI, we do not know what kinds of genes we should be searching for. In the first stage of our study, we therefore started by trying to identify which chromosomes the genes might lie on. We did this by carrying out a complete genome scan of all 23 human chromosomes.

We used DNA from 98 families with family members affected by SLI. The techniques we used for this research are based on the premise that, if affected children share the genes that cause SLI, then at the position of these genes, they will be genetically more similar than we would normally expect unrelated people to be.

We identified two regions that we think might contain genes that make people prone to SLI: SLI1 on chromosomes 16 and SLI2 on chromosome 19. The results of the first stage of our project were published in 2002.

However, the techniques used to identify these regions on chromosome 16 and 19 as being potentially linked to SLI are statistical methods. At best, these only enable us to say that a certain genetic region is likely to contain a gene involved in the disorder under study. The more families we are able to include in the study, the more confident we will be that we are focussing on the correct genetic regions.

In the second stage of our study we included an additional 86 families with family members affected by SLI. Once again we found that regions of chromosomes 16 and 19 were more similar in individuals with language problems than we would expect by chance alone, therefore making it very likely that these chromosomes are really of general importance in SLI. The results of the second stage of our project were published in 2004.

FURTHER DETAILS on our initial studies

4.3 Current research

Our initial studies allowed us to narrow down the search for SLI susceptibility genes from 23 chromosomes to 2 regions on 2 chromosomes: SLI1 (chromosome 16) and SLI2 (chromosome 19). In 2007, published the results of a new study that provides further evidence for the involvement of these two genetic regions in susceptibility to language impairments.

However, as there are hundreds of genes within the SLI1 and SLI2 regions, there is still a lot of work to be done before we will be able to identify the specific genes underlie SLI. Our approach is to pick out the genes that are important in brain development and study these first. We are looking for changes or variations in these genes, which might affect how the gene works.

We are currently studying in more detail the regions identified on chromosome 16. This will help us to narrow down the regions which we think contain the genes.

MORE DETAILS HERE ON CURRENT RESEARCH

5. Funders

The SLI project is funded by a grant from the Wellcome Trust

6. Collaborators

Our studies were carried out in collaboration with the SLI Consortium (SLIC), a group of scientists in the UK who are working together to unravel the role that genetics plays in the development of SLI.

7. Publications

Most recent publications:

2008

A functional genetic link between distinct developmental language disorders (2008)
SC. Vernes, DF Newbury, BS Abrahams, L Winchester, J Nicod, M Groszer, M Alarcón, PL Oliver, KE Davies, D H Geschwind, AP Monaco & SE Fisher
New England Journal of Medicine, 2008; 359

[PubMed record] [PDF in New England Journal of Medicine]

2007

Genetic and phenotypic effects of phonological short-term memory and grammatical morphology in specific language impairment (2007)

Falcaro M, Pickles A, Newbury DF, Addis L, Banfield E, Fisher SE, Monaco AP, Simkin Z, Conti-Ramsden G; The SLI Consortium.

Genes Brain Behav. 2007 Nov 12; [Epub ahead of print]

[PubMed record] [Abstract in Genes, brain, and behavior]

 

Multivariate Linkage Analysis of Specific Language Impairment (SLI) (2007).

Monaco AP (SLIC). Annals of Human Genetics, 2007 Mar 27: 39
[PubMed record] [complete article from journal website]

8. Links

• SLI Consortium (SLIC)

9. Contact

For all enquiries, please contact Dr Dianne Newbury at: diane@well.ox.ac.uk