WTCHGNewbury Group

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*NEWS* CONFER

I was really happy to attend the CONFER conference this weekend with Nessa Carey and Oliver James. I got to meet lots of interesting psychotherapists and we debated whether genes contribute to mental disorders. You can find a copy of my talk in the presentations section of our website.

Research 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 learning disability.

Children with SLI might have problems understanding (receptive) or using (expressive) language. The diagnostic guidelines for SLI can be found here.

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?

Chromosomes spread on a slide

Studies show that SLI runs in families - 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 (at least in part) 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 sometimes 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 contribute to SLI or how the inheritance of language problems work. We think that SLI is probably a complex genetic disorder. This means that there are certain combinations of common, normal, genetic variantions which make some individuals particularly susceptible to language problems during language development. Working closely with other collaborators active in this field, we aim to identify specific genetic variants that cause this predisposition and to investigate the kinds of biological processes that they take part in.

Publications in Plain English

For each of the primary research papers coming from our lab, we will provide an infographic which summarises the main conclusions from the paper. Each infographic is followed by a link from which you can download a one-page summary describing the aims of the paper and it's main findings.

All our publications are open access so, if after reading the summary you would like to read the full paper, you can find a link on our scientific publications page.

 

March 2015 - Investigation of the Robinson Crusoe Population

In this study, we looked at genetic variation in a particular population of people affected by language impairment. This population live on the Robinson Crusoe Island in Chile.

RC1

In this study, we found a change in the genetic sequence that was particularly common in people living on the Robinson Crusoe Island. The bluer the country, the more common the variant. The numbers under the country show the percentage of the population estimated to carry the variant.

RC2

More importantly, we found that this variant was particularly common in inhabitants of the Robinson Crusoe Island who were affected by language impairment.

A more detailed description of the study and it's findings can be downloaded here.

 

January 2015 - Amount of rearranged DNA in children affected by SLI.

In this study, we measured the level of DNA reorganisation in children affected by SLI and their family members and compared it to members of the general population.

We found that:

CNVs

Amount of rearranged DNA in individuals affected by SLI and their family members.

The length of the DNA strand represents the average amount of rearranged DNA in the group shown.

The number above shows the number of base pairs of DNA that is rearranged.

 

 

 

A more detailed description of the study and it's findings can be downloaded here.

Podcasts and Presentations

You can take a lightning tour of the lab.

We have podcasts discussing the research in our lab:

A podcast of the Robinson Crusoe project (mp4).

A general podcast describing our research interests (mp4).

And a scientific presentation of our research (from ICHG 2011, mp4 format).

We often give presentations at conferences or meetings. Details can be found on our presentations page.

Recent Publications

All our publications are open access. Our publications from this year are shown below. For a full list of publications, please see publications page

2016

Pettigrew KA, Frinton E, Nudel R, Chan MT, Thompson P, Hayiou-Thomas ME, Talcott JB, Stein J, Monaco AP, Hulme C, Snowling MJ, Newbury DF, Paracchini S. (2016) Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes. J Neurodev Disord. 2016 Jun 14;8:24. PMID:27307794 [pdf]

Shore R, Covill L, Pettigrew KA, Brandler WM, Diaz R, Xu Y, Tello JA, Talcott JB, Newbury DF, Stein J, Monaco AP, Paracchini S. The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts. Hum Mol Genet 2016 Feb 21. PMID:26908617 [pdf]

Prekovic S, Đurđević DF, Csifcsák G, Šveljo O, Stojković O, Janković M, Koprivšek K, Covill LE, Lučić M, Van den Broeck T, Helsen C, Ceroni F, Claessens F, Newbury DF. Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation. Sci Rep. 2016 Feb 3;6:20369. PMID:26838027 [pdf].

2015

Howey R, Mamasoula C, Töpf A, Nudel R, Goodship JA, Keavney BD, Cordell HJ. Increased Power for Detection of Parent-of-Origin Effects via the Use of Haplotype Estimation. Am J Hum Genet. 2015 Sep 3;97(3):419-34. PMID:26320892 [pdf].

Nudel R, Ceroni F, Simpson N, Newbury DF (2015) The genetics of specific language impairment (SLI). In S Stavrakaki (Ed.), Specific Language Impairment (pp.7-34). John Benjamins Publishing Company. Language Acquisition and Language Disorders Series. 2015. ISBN 9789027253217

Pettigrew KA, Reeves E, Leavett R, Hayiou-Thomas ME, Sharma A, Simpson NH, Martinelli A, Thompson P, Hulme C, Snowling MJ, Newbury DF, Paracchini S. Copy Number Variation Screen Identifies a Rare De Novo Deletion at Chromosome 15q13.1-13.3 in a Child with Language Impairment. PLoS One. 2015 Aug 11;10(8):e0134997. PMID:26262844 [pdf]

Moralli D, Nudel R, Chan MT, Green CM, Volpi EV, Benítez-Burraco A, Newbury DF, García-Bellido P. Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2. Mol Cytogenet. 2015;8:36. PMID:26060509 [pdf]

Pettigrew KA, Fajutrao Valles SF, Moll K, Northstone K, Ring S, Pennell C, Wang C, Leavett R, Hayiou-Thomas ME, Thompson P, Simpson NH, Fisher SE; SLI Consortium, Whitehouse AJ, Snowling MJ, Newbury DF, Paracchini S. Lack of replication for the myosin-18B association with mathematical ability in independent cohorts. Genes Brain Behav. 2015 Apr;14(4):369-76. PMID:25778778 [pdf]

Villanueva P, Nudel R, Hoischen A, Fernández MA, Simpson NH, Gilissen C, Reader RH, Jara L, Echeverry MM, Francks C, Baird G, Conti-Ramsden G, O’Hare A, Bolton PF, Hennessy ER, the SLI Consortium, Palomino H, Carvajal-Carmona L, Veltman JA, Cazier JB, De Barbieri Z, Fisher SE, Newbury DF. Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment. PLoS Genetics. 2015 Mar 17;11(3):e1004925. PMID:25781923 [pdf]

Simpson NH, Ceroni F, Reader RH, Covill LE, Knight JC; the SLI Consortium, Hennessy ER, Bolton PF, Conti-Ramsden G, O'Hare A, Baird G, Fisher SE, Newbury DF. Genome-wide analysis identifies a role for common copy number variants in specific language impairment. Eur J Hum Genet. 2015 Jan 14. [Epub ahead of print]. PMID:25585696 [pdf]

Funding Sources

The SLI research project is funded by the Medical Research Council (MRC), the John Fell Fund and St John's College, Oxford.

Research Area

Neurogenetics.

Keywords

Specific Language Impairment (SLI), neurogenetics, developmental disorders.