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Department of Biological and Medical Sciences
Faculty of Health and Life Sciences
Gipsy Lane, Sinclair, S306b
I am a senior lecturer on the MSc Medical Genetics and Genomics programme and I am principal investigator of a research lab in the Department of Health and Life Sciences.
P10112: Molecular Basis of Human Genetic Disease
P10114: Clinical Genetics and Diagnostics
P10199: MSc research project
U14520: Molecular Biology and Genetics
U14592: Molecular Medicine
U14675: Experimental Based Medicine and Diagnostics
U14699: Undergraduate research projects
Research in my lab centres around genetic contributions to speech, language and Communication Disorders (SLCDs). A recent study found that, at school entry in the UK, approximately 10% of children are affected by speech, language or communication impairments (Norbury et al., 2016). As a group these children are less likely to meet educational targets (Norbury et al., 2015) and more likely to display symptoms of social, emotional and behavioural problems when compared to their peers (Norbury et al., 2016).
But yet, we do not know why some children have language difficulties or how these difficulties relate to other aspects of neurodevelopment and behaviour. In our lab, we are trying to identify genetic factors that might play a role in these disorders. We investigate this problem through a mixture of research questions and by studying individuals, families and populations.
This research is important because it will help us to understand why some children have language difficulties and what brain processes are important in language learning. It may allow us to identify new kinds of language disorders and will clarify the relationships between language impairment and other developmental disorders.
Hayley Mountford (post-doc) p0083144
Lidiya Nevedska (PhD student) 16034238
Nuala Simpson (post-doc) p0084691
Research Excellence (CRF) award – Functional characterisation of RIC3 in backwards speech. Aug 2016-Jan 2017
ESRC Newton Award - A language and reading intervention programme for Chile, piloted in the Robinson Crusoe population. Feb 2016 – Oct 2018
Studies show that developmental language disorders run in families - a brother or sister of someone who has already been diagnosed 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 causes the language disorder; or (2) Developmental language disorders are genetic and is therefore caused (at least in part) by the genes passed on from parents to children.
Although there is strong evidence for the role of a genetic component in language disorder, we do not know which genes contribute to this disorder or how the inheritance of language problems work. In most cases, it is likely that several genes combine to bring about a heightened risk of disorder. This is known as a complex genetic disorder. 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.
The work in our lab is split into different project areas. You can find out more about each area on our research website.
Robinson Crusoe Island is a geographically and socially isolated settlement located over 600km west of the Port of Valparíso, Chile. An unusually high incidence (30%) of the Chilean equivalent of developmental language disorder (TEL) has been reported in Islander children, with 90% of these affected children found to be direct descendants of a pair of original founder-brothers, therefore strongly suggesting a shared genetic basis.
Here we utilise whole-genome sequencing to investigate potential underlying variants in a panel of thirty-four genes known to play a role in language disorders, in seven TEL affected and ten unaffected islanders. We use this targeted approach to look for rare, shared variants that may underlie the diagnosis of TEL in a Mendelian genetic model. We go on to test whether the overall burden of rare variants is enriched in individuals affected by TEL or with Islanders related to the founder-brother lineage.
In the absence of explanatory rare variants, we further investigate these candidate genes within a complex model of inheritance, where inheriting a small number of moderate impact common variants may increase susceptibility of developing TEL. We examine if any variants segregate with affection status or with founder-brother-related status, and therefore may increase risk of developing a language disorder. Finally, we perform a pooled, gene-based tests to evaluate relationships between combined variation across candidate genes and TEL affection status.
Here we report a comprehensive examination of genes directly implicated in language-related mechanisms to identify ‘low hanging fruit’ of causative monogenic Mendelian variants, and complex association model of increased susceptibility in developmental language disorder found on Robinson Crusoe Island.
Background: Generalized Structured Component Analysis (GSCA) is a component-based alternative to traditional covariance-based structural equation modelling. This method has previously been applied to test for association between candidate genes and clinical phenotypes, contrasting with traditional genetic association analyses that adopt univariate testing of many individual single nucleotide polymorphisms (SNPs) with correction for multiple testing.Methods: We first evaluate the ability of the GSCA method to replicate two previous findings from a genetics association study of developmental language disorders. We then present the results of a simulation study to test the validity of the GSCA method under more restrictive data conditions, using smaller sample sizes and larger numbers of SNPs than have previously been investigated. Finally, we compare GSCA performance against univariate association analysis conducted using PLINK v1.9.Results: Results from simulations show that power to detect effects depends not just on sample size, but also on the ratio of SNPs with effect to number of SNPs tested within a gene. Inclusion of many SNPs in a model dilutes true effects.Conclusions: We propose that GSCA is a useful method for replication studies, when candidate SNPs have been identified, but should not be used for exploratory analysis.
Purpose: Children with poor language tend to have worse psychosocial outcomes compared to their typically developing peers. The most common explanations for such adversities focus on developmental psychological processes whereby poor language triggers psychosocial difficulties. Here we investigate the possibility of shared biological effects by considering whether the same genetic variants which are thought to influence language development are also predictors of elevated psychosocial difficulties during childhood.
Method: Using data from the UK based Avon Longitudinal Study of Parents and Children (ALSPAC) we created a number of multi-SNP polygenic profile scores, based on language and reading candidate genes (ATP2C2, CMIP, CNTNAP2, DCDC2, FOXP2, & KIAA0319, 1229 SNPs) in a sample of 5,435 children.
Results: A polygenic profile score for expressive language (8 years) that was created in a discovery sample (n=2,718), predicted not only expressive language (8 years), but also peer problems (11 years) in a replication sample (n=2,717).
Conclusions: These findings provide a proof of concept for the use of such a polygenic approach in child language research when larger datasets become available. Our indicative findings suggest consideration should be given to concurrent intervention targeting both linguistic and psychosocial development as early language interventions may not stave off later psychosocial difficulties in children.
Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions.
Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis.
Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association.
Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome.
This chapter focuses on the understanding of the role of genetics in language and explores how genetics contribute to language, and shows how new genetic techniques can offer inroads into the molecular basis of language acquisition. It discusses some of the key findings of gene x environment studies and provides a snapshot of the understanding in the field, considering some of the limitations of the type of study design. The chapter describes the field of play in the genetics of language acquisition and explains the heritability of language and the role of family and twin studies in the understanding of language. It also explores the inheritance mechanisms that are implicated in language development. The chapter considers how modern DNA sequencing approaches are revolutionizing the field of language genetics. Heritability studies have provided many key insights into the genetics of both language acquisition and language disorders. Insights into mechanisms can also come from the opposite end of the language ability spectrum.
Gene mapping (linkage, association, sequencing)
Speech and language disorders
MRC College of Reviewers for the Newton Fund.
International Scientific Advisory board for the University of Connecticut
Scientific Advisor for the Press and Information Office at the University of Oxford.
University Reseach Lecturer at Oxford University
MRC career Development Fellow
Junior Research Fellow, St Johns College
Tutorial Fellow, Somerville College
See http://www.well.ox.ac.uk/webcasts-podcasts for podcasts and interviews