On this page, you will find abstracts and supporting material for presentations given by the Newbury group at recent conferences.

Confer Do Genes (ever) Determine our Mental Health? 2016

I presented at a Confer debate in June 2016. You can download a pdf of my presentation at Confer here.

The nature-versus-nurture debate is always of great fascination to anyone wishing to discover the means by which we can best facilitate growth and health. Today, now that discussion is powered by the findings of the two human genome projects, we should have much better evidence for understanding the proportional roles of environment-versus-biological heredity. Of obvious great interest to all those concerned with health is how to get a better understanding of the major illnesses and their aetiology - particularly those with clear biological mechanisms. But what does research tell us about psychological issues? Are they influenced by DNA? And can they be reduced to physiology? Where do personality, emotional disposition or disorders of mental health originate? This day invites three presenters to examine the evidence.

European Society of Human Genetics 2016

Two young investigators from our lab presented at the European Society of Human Genetics in Barcelona.

Fabiola Ceroni presented a poster describing her findings in a case study of Childhood Disintegrative Disorder (CDD), a rare and devastating form of autism with regression.

Stefan Prekovic presented a poster describing his characterisation of a family with the rare ability to speak backwards. This work formed the basis of a paper in Scientific Reports earlier this year.

Abstracts for both posters are given below

Title: P09.045A - Case report: exome sequencing of a family with childhood disintegrative disorder.
Keywords: Childhood disintegrative disorder; PCM1; ALMS1
Authors: F. Ceroni1, M. Absoud2, G. Baird2, A. Velayos-Baeza1, D. Newbury1;
1Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom, 2Guy's & St Thomas’ NHS Foundation Trust, London, United Kingdom.
Abstract: Childhood disintegrative disorder (CDD) is a very rare but devastating neurodevelopmental condition characterised by rapid and severe decline in developmental skills (communication, play, self-care, cognition) in children with apparently normal previous development for the first 2 years of life. The regression results in significant long-term impairments in social communication skills, similar to features of Autism Spectrum Disorder (ASD) with severe intellectual disability. Extensive neurometabolic investigations usually do not reveal an underlying aetiology. We report an exome sequencing study of a family with two affected children and neurotypical parents. Pathway analyses of rare and potentially damaging variants highlighted two variants in genes involved in intracellular trafficking and recruitment of proteins to the centrosome: both children carry a maternal stop codon in PCM1 (NP_006188, p.E1912X) and a paternal nonsynonymous change in ALMS1 (NP_055935, p.S763N). PCM1 is an essential component of the centriolar satellites and interacts with several proteins, including DISC1 (disrupted in schizophrenia 1) and BBS4 (Bardet-Biedl Syndrome 4). Mutations in ALMS1 can cause Alström Syndrome, a rare recessive multi-system ciliopathy, closely related to the Bardet-Biedl Syndrome (BBS). The biological functions of ALMS1 are still being elucidated, but roles in cilium function and maintenance, intracellular trafficking, signaling pathways and cell cycle regulation have been suggested. Although the functional interaction between ALMS1 and PCM1 needs to be further investigated, the participation of the two proteins to the same cellular network, which has been previously implicated in other neurodevelopmental disorders, led us to hypothesize a possible compound effect of the two identified variants
Title: P09.143 - Multidisciplinary investigation of backward-speech trait suggests a link between RIC3, RIPK1, ZBED5 and working memory
Keywords: speech; working memory; RIC3
Authors: S. Prekovic1, D. Filipović Đurđević2,3, G. Csifcsák4, O. Sveljo5,6, O. Stojković7, F. Ceroni8, D. F. Newbury8;
1Faculty of Medicine, KU Leuven, Leuven, Belgium, 2Faculty of Philosophy, University of Novi Sad, Novi Sad, Serbia, 3Faculty of Philosophy, University of Belgrade, Belgrade, Serbia, 4Institute of Psychology, Faculty of Arts, University of Szeged, Szeged, Hungary, 5Diagnostic Imaging Center, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, 6Faculty of Technical Sciences, University of Novi Sad, Novi Sad, Serbia, 7Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 8Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, United Kingdom.
Abstract: Introduction: Working memory is essential for the development of many language-related traits. It has been suggested that the rare trait of backward-speaking is linked to working memory. This trait is described as an ability to spontaneously and accurately reverse words. Here we describe individuals (the father and daughter) from a Serbian family who have the ability to speak backward voluntarily.
Materials and Methods: We employed behavioral tests to describe the trait and neuroimaging (EEG and fMRI) to study the neural processing behind backward-speech. Moreover, we investigated coding sequence changes through exome sequencing and copy number variations using SNP array data in this family.
Results: Behavioral data suggests that backward-speech loads heavily upon working memory. Event-related potentials above the frontal lobe are affected by word reversal and the maintenance of backward-words in working memory. fMRI revealed that the left fusiform gyrus may facilitate backward-speech in the daughter. Exome sequencing identified three novel coding variants of potential significance in the RIC3, RIPK1 and ZBED5 genes.
Conclusions: Our data suggest that in the daughter, backward-speech is afforded by an extraordinary working memory capacity. We hypothesize that this is served by cholinergic projections from the basal forebrain to the frontal cortex and supported by visual semantic loops within the left fusiform gyrus and that these processes may be mediated by a genetic mutation in the RIC3 gene which encodes a chaperone for nicotinic acetylcholine receptors.
This research was supported by grants from MSTD (179006, 179033 and 175093), NBRP (KTIA_13_NAP-A-II/20), and MRC (G1000569/1 and MR/J003719/1).

Oxford Neuroscience Symposium 2016

In March 2016, Hayley Mountford presented a poster describing her work at the Oxford Neuroscience Symposium.

Building the Brain, Genetics Society Conference at the Royal Society, London 2015

I presented an overview of the genetics of speech and language disorders at the Building the Brain conference in December 2015.

Genetic contributions to Specific Language Impairment (SLI).

Disorders of speech and language are common in childhood and presumably arise from subtle disturbances during brain development. Nonetheless, we have little understanding as to the underlying pathology of this group of disorders. They are highly heterogeneous and in the majority of cases are genetically complex. In this talk, I will provide an overview of genetic studies of speech and language disorders. I will discuss how increases in sample sizes and the application of new technologies may highlight conserved mechanisms of language development providing a better understanding of the biological contributions to these disorders.

American Society of Human Genetics 2015

We were co-authors on a paper presented at the American Society of Human Genetics by Heather Cordell's group at the University of Newcastle. The poster described the use of haplotype information to increase power to detect parent of origin effects. Details of the study and methods can be found in an American Journal of Human Genetics paper. This work was also presented at the International Genetic Epidemiology Society in October 2015. An abstract for the poster is below:

Increased power for detection of parent-of-origin effects via the use of haplotype estimation

Richard Howey (1), Chrysovalanto Mamasoula (1,2), Ana Töpf (1), Ron Nudel (3), Dianne F. Newbury (3), Simon E. Fisher (4,5), Judith A. Goodship (1), Bernard D. Keavney (1,6), Heather J. Cordell (1)

1 Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK

2 Institute of Health and Society, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK

3 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK

4 Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands

5 Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands

6 Institute of Cardiovascular Sciences, University of Manchester, Manchester, M13 9NT, UK

Parent-of-origin (or imprinting) effects relate to the situation where traits are influenced by the allele inherited from only one parent, with the allele from the other parent having little or no effect. Given SNP genotype data from case/parent trios, the parent-of-origin of each allele in the offspring can often be deduced unambiguously; however this is not true when all three individuals are heterozygous. Most existing methods for investigating parent-of-origin effects operate on a SNP by SNP basis and either perform some sort of “averaging" over the possible parental transmissions or else discard ambiguous trios. If the correct parent-of-origin at a SNP could be determined, this would provide extra information and increase the power to detect effects of imprinting. We propose making use of the surrounding SNP information, via haplotype estimation, to improve estimation of parent-of-origin at a test SNP for case/parent trios, case/mother duos and case/father duos. This extra information is then used in a multinomial modelling approach to estimate parent-of-origin effects at the test SNP. We show through computer simulations that our approach has increased power over previous approaches, particularly when the data consist only of duos. We apply our method to two real data sets and find a decrease in significance of p-values in genomic regions previously thought to possibly harbour imprinting effects, thus weakening the evidence that such effects actually exist in these regions, although some regions remained more significant than expected.

Attention, Brain and Cognitive Development 2015

I presented a poster at the attention, brain and development seminar in Oxford (June 22nd 2015) describing our findings regarding season of birth effects in the ALSPAC cohort. This work was completed by Laura Covill, a gap year student in our lab. The abstract is below:

Relationship Between Season of Birth And Educational Attainment in ALPSAC Support Existence of Relative Age Effect

DF Newbury, LE Covill, NH Simpson, G Davey Smith & S Paracchini

It has been suggested that season-of-birth can affect scholastic achievement and the chances of being diagnosed with a neurodevelopmental disorder. In this study, we investigate the relationship between season of birth, the presence of neurodevelopmental disorders, and scholastic attainment in children, in the ALSPAC child population cohort. We find that, as a group, Summer-born children perform better in tests of IQ, reading and spelling proficiency. Despite this, Summer-born children are more likely to be diagnosed with specific learning disorders, particularly those centred on reading and writing ability, and achieve fewer GCSEs than their counterparts. These effects are small in real terms but consistent across time points. Our data show that Summer-born children are at a disadvantage when directly compared to their classmates in subjective examinations, which do not adjust for absolute age. We suggest that such disadvantages could be offset by the use of age-normalised testing in state examinations.

European Society of Human Genetics 2015

We were co-authors on two presentations at the European Society of Human Genetics in June 2015.

Sameuelle Fajutrao Valles described her work on associtions across MYO18B and dyscalculia and Robert Shore described his work on the PCSK6 gene. Both researchers are from Silvia Paracchini's lab at the University of St Andrews. Abstracts are below.

Title: PS08.15 - Myosin-18B and mathematical ability in independent cohorts: lack of replication in independent cohorts
Keywords: dyscalculia; myosin-18B; replication
Authors: S. Fajutrao Valles1, K. A. Pettigrew1, K. Moll2, K. Northstone3, S. Ring3, C. Pennell4, C. Wang4, R. Leavett5, M. E. Hayiou-Thomas5, P. Thompson6, N. H. Simpson7, S. E. Fisher8, The SLI Consortium, A. J. O. Whitehouse9, M. J. Snowling10, D. F. Newbury10, S. Paracchini1;
1School of Medicine, University of St Andrews, St Andrews, United Kingdom, 2Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany, 3School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom, 4School of Women's and Infants' Health, University of Western Australia, Crawley, Australia, 5Department of Psychology, University of York, York, United Kingdom, 6Department of Experimental Psychology, University of Oxford, St Andrews, United Kingdom, 7Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 8Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands, 9Telethon Kids Institute, University of Western Australia, Crawley, Australia, 10St. John's College, University of Oxford, Oxford, United Kingdom.
Abstract: Dyscalculia (or mathematical ability) is a condition where mathematical ability is severely impaired. Twin studies suggest that it is partly caused by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the Myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities. However, this association has not been replicated before. We conducted a replication analysis in different cohorts characterised with maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=3819), which was adequately powered for this analysis. We tested additional cohorts including the York Cohort (N=291), the Specific Language Impairment Consortium (SLIC) (N=367) and the Raine Cohort (N=667). Cohorts were stratified for a definition of dyslexia where possible. We did not observe any associations between rs133885 in Myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results then suggest that the Myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities.
SP is a Royal Society University Research Fellow. The study in the ALSPAC cohort was supported by [Grant number G0800523/8647] and [Grant ref:102215/2/13/2]. The Raine study was supported by [Grant 572613] and [Grant MOP 82893]. The work in the University of Oxford was supported by [Grant number 1004065] [G1000569/1 and MR/J003719/1] and [090532/Z/09/Z]. The study in the SLIC cohort was supported by [060774 and 076566].
Title: PS09.097 - The PCSK6 intronic region associated with handedness controls expression of a novel shorter isoform
Keywords: PCSK6; Handedness; Dyslexia
Authors: R. J. Shore1, K. Pettigrew1, R. Diaz1, Y. Xu1, E. Wootton1, L. Covill2, W. Brandler2, J. B. Talcott3, D. F. Newbury2, A. Monaco2, J. Stein4, S. Paracchini1;
1School of Medicine, University of St Andrews, St Andrews, United Kingdom, 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 3School of Life and Health Sciences, Aston University, Birmingham, United Kingdom, 4Dept of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom.
Abstract: We recently reported the first gene, PCSK6, associated with handedness at genome-wide significance level (P< 0.5*10-8, Brandler et al. 2013). A Variable Number Tandem Repeat (VNTR) within the same PCSK6 locus has been found to be associated with degree of handedness in an independent study (Arning et al. 2013). Interestingly, PCSK6 is known to activate NODAL, a morphogen involved in a highly conserved pathway known to regulate left/right body axis determination. Our previous data suggest these pathways controlling development of LR asymmetry in the body are reused for brain midline development, which in turn influence functional asymmetries such as handedness (Brandler and Paracchini 2014). All previous most significant associations fall within a linkage disequilibrium (LD) block containing a secondary promoter our data show to be bidirectional in nature and controlling transcription of both a novel PCSK6 isoform and a long non-coding antisense RNA. Taking forward previous GWAS findings, we have conducted a detailed functional analysis using a combination of further genetic analysis, in-silico predictions, and molecular assays. Our functional studies support an allele-specific effect on transcription factor binding affinity for a previous top-associated SNP rs11855425 however our genetic data could not find any evidence supporting a VNTR role. With this study we have dissected the molecular mechanisms underlying the PCSK6 association with handedness, indicating the regulatory effect the region has on specific RNA isoforms. Future work will focus on understanding the function of the novel shorter PCSK6 isoform and confirming the identity and role of the transcription factors binding at the secondary promoter.Neurodys018696, WT090532/Z/09/Z, MRCG090074791070, G1000569/1 and MR/J003719/1.

British Dyslexia Association 2014

I presented a powerpoint presentation as part of a symposium enitiled "Genetic and environmental influences on reading (dis)ability" at the British Dyslexia Association meeting in Guildford (27th March 2014). My abstract is below.


Specific Language Impairment (SLI) is defined as a substantial deficit in oral language skills despite adequate intelligence and opportunity. This common childhood condition has a high level of comorbidity with the written language disorder, developmental dyslexia and both show evidence for the existence of strong genetic contributions.Using genetic studies of individuals with speech and language impairments, we have identified common variants and structural rearrangements which may contribute to susceptibility to SLI. We have investigated variations across SLI and dyslexia candidate genes in groups of children affected by oral or written language disorders and find evidence for the existence of complex genetic relationships between these disorders.

Celebrating a century of international collaboration - MRC - 2013

We won first prize in an MRC competition for Internation collaborative research. My Chilean collaborator Pia Villaneuva and I presented a poster at the Royal society in London as part of this competition.

European Society of Human Genetics 2013

Title: P06.47 - Increased prevalence of sex chromosome aneuploidies in Specific Language Impairment and Dyslexia.
Keywords: specific language impairment; dyslexia; sex chromosome aneuploidy
Authors: N. H. Simpson1, L. Addis2, W. M. Brandler1, V. Slonims3, A. Clark4, J. Watson4, T. S. Scerri5, J. Stein6, J. B. Talcott7, G. Conti-Ramsden8, A. O'Hare9, G. Baird3, J. C. Knight1, S. Paracchini10, S. E. Fisher11,12, D. F. Newbury1, S. L. I. Consortium1;
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 2Institute of Psychiatry, London, United Kingdom, 3Newcomen Centre, Guy’s Hospital, London, United Kingdom, 4Queen Margaret University, Edinburgh, United Kingdom, 5The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, 6University of Oxford, Oxford, United Kingdom, 7Aston Univeristy, Birmingham, United Kingdom, 8University of Manchester, Manchester, United Kingdom, 9Univeristy of Edinburgh, Edinburgh, United Kingdom, 10University of St Andrews, St Andrews, United Kingdom, 11Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands, 12Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Abstract: Specific language impairment (SLI) and dyslexia are developmental disorders exhibiting deficits of spoken (SLI) or written (dyslexia) language in the absence of comorbid neurological deficits, despite adequate intelligence and education. Sex chromosome aneuploidies increase the risk of spoken or written language disorders but, compared to other developmental disorders, e.g. autism, individuals with SLI or dyslexia do not routinely undergo cytogenetic analysis.
To assess the frequency of sex chromosome aneuploidies within individuals with SLI or dyslexia, genome-wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with SLI referred to a child development centre (87 probands), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands) and a set of individuals with dyslexia (310 probands).
In the clinical SLI cohort, three abnormal karyotypic results were identified in probands, representing a proband yield of 3.4%. In the SLI replication cohort six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aberrations were found giving a lower proband yield of 0.6%. In total two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome) and one proposed XO/XY mosaic karyotype were identified.
The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.1%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems, enabling therapies associated with these sex chromosome abnormalities to be implemented more promptly.

Poster presentation [pdf]


Title: P06.48 - Identification of a genomic homozygous deletion of ZNF277 in a child with SLI
Keywords: Specific Language Impairment (SLI); microdeletion; AUTS1
Authors: F. Ceroni1, N. H. Simpson2, C. Francks3,4, G. Baird5, G. Conti-Ramsden6, A. E. O'Hare7, E. Maestrini1, E. Bacchelli1, S. E. Fisher3,4, D. F. Newbury2, I. M.G.S.A.C1,2, S. L. I. Consortium2;
1Dipartimento di Farmacia e Biotecnologie, University of Bologna, Bologna, Italy, 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 3Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands, 4Donders Institute for Brain, Cognition & Behaviour, Nijmegen, Netherlands, 5Guy's & St Thomas NHS Foundation Trust, Newcomen Children's Neurosciences Centre, St Thomas' Hospital, London, United Kingdom, 6School of Psychological Sciences, The University of Manchester, Manchester, United Kingdom, 7Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
Abstract: Specific language impairment (SLI) is a common neurodevelopmental disorder in which language abilities are below age expectations, in the absence of explanatory environmental or medical conditions, such as hearing loss, intellectual disability or autism. SLI affects 3-7% of English-speaking pre-school children. During a genome-wide CNV scan using a multi-algorithm approach, we identified a homozygous deletion of 21,379bp in the ZNF277 gene, overlapping exon 5, in an individual with severe receptive and expressive SLI. This deletion was of particular interest as it falls within the AUTS1 region of linkage to autism. ZNF277 flanks the DOCK4 and IMMP2L genes, which have been suggested to play a role in autistic spectrum disorders (ASD). We therefore screened cohorts of children with SLI or ASD and control subjects for the presence of ZNF277 deletions. We observed an increased frequency of ZNF277 deletions in probands with SLI (6/318, 1.9%) compared to both probands with ASD (1/253, 0.4%) and independent controls (2/224, 0.8%). We performed quantitative PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in lymphoblastoid cell lines carrying either a DOCK4 microdeletion or a ZNF277 microdeletion. We found that, while ZNF277 microdeletions affect the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Similarly, DOCK4 microdeletions do not affect the expression levels of ZNF277. Given these findings, we postulate that ZNF277 microdeletions may contribute to the risk of speech and language impairments in a manner that is independent of the autism risks previously described in this region.

Poster presentation [pdf]

Behavior Genetics Association 2012

Exome sequencing of an isolated Chilean population affected by Specific Language Impairment (SLI).
D. F. Newbury1, A. Hoischen2, R. Nudel1, C. Gilissen2, L. Carvajal-Carmona1,3, M. M. Echeverry3, L. Jara4, Z. De Barbieri5, H. M. Palomino6, M. A. Fernández5, H. Palomino6, J. Veltman2, A. P. Monaco1, P. Villanueva4,5,6, S. E. Fisher1,7
1) Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom;
2) Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;
3) Department of Biology, University of Tolima, Tolima, Colombia;
4) Human Genetics Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile;
5) School of Speech and Hearing Therapy, Faculty of Medicine, University of Chile, Santiago, Chile;
6) Department of Child and Dental Maxillary Orthopedics, Faculty of Dentistry, University of Chile, Santiago, Chile;
7) Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
Speech and language impairments that are a primary deficit and have no obvious cause (e.g. a comorbid neurological disorder like autism) are diagnosed as Specific Language Impairment (SLI). SLI affects 5-8% of preschool children and represents a lifelong disability associated with an increased risk of behavioural disorders, social problems and literacy deficits. SLI is highly heritable and twin studies indicate a strong genetic basis. Nonetheless, the underlying genetic mechanisms are expected to be multifactorial and, to date, only three risk variants have been identified. One way to increase the power to detect contributory genetic factors is to study isolated populations derived from relatively recent shared ancestors (founder populations). In 2008, Villanueva described a founder population with a particularly high incidence of SLI (10 times that expected). They inhabit the Robinson Crusoe Island, which lies 677km to the west of Chileand was colonised in the late 19th century by 8 European and Amerindian families. 77% of the current island population have a colonising surname and 14% of marriages involve consanguineous unions. More than 80% of language impaired individuals can be traced to a pair of founder brothers. This population thus has a short (5-generations) and well-documented history and represents a unique resource which could make valuable contributions to the elucidation of genetic mechanisms underpinning SLI.
We applied exome sequencing technologies to five language-impaired individuals from this population and identified nine non-synonymous coding changes or splice site mutations that were present in at least three of the five affected individuals sequenced. Sequencing of the entire cohort identified a single non-synonymous coding change that was significantly more frequent in cases than controls (genotype frequencies of 46% and 11% respectively, p=4.48 × 10-5). We suggest that this rare coding variant may contribute to the elevated frequency of SLI in this population.

Poster Presentation [pdf]

European Society of Human Genetics 2012

Title: P09.126 - Investigating copy number variants within a cohort of individuals with specific language impairment
Keywords: specific language impairment; copy number variation; developmental disorder
Authors: Nuala H. Simpson1, Fabiola Ceroni1, Clyde Francks2, Samantha J. L. Knight1, Anthony P. Monaco1, Simon Fisher2, Dianne Newbury1, S L. I. Consortium1.
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 2Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.
Abstract: Specific language impairment (SLI) is a developmental language disorder that, in the absence of any comorbid neurological deficits, affects an individual’s spoken and/or receptive language despite adequate intelligence and accessibility to learning. SLI is a common childhood disorder with an estimated prevalence in pre-school children of up to 7%. It is a complex genetic disorder that is closely related to autism, dyslexia and ADHD. SLI has a high genetic component with twin studies finding a monozygotic concordance rate of up to 70%. Recent studies of neurodevelopmental disorders have implicated copy number variants (CNVs) in conditions such as autism, intellectual disability and ADHD. Therefore a study of CNVs within families containing individuals with SLI is currently being performed. The SLI consortium has collected a cohort of samples from across the UK that have been phenotypically well characterised for language. 176 of these families containing 186 individuals with SLI have been genotyped using the Illumina HumanOmniExpress beadchip that contains more than 700,000 SNPs. The SNP data is being used to identify CNVs across the genome using the copy number detection algorithms QuantiSNP and PennCNV. Data will be presented, for example, of the relative burden of CNVs in cases compared to their unaffected siblings and of novel variants. CNVs of interest are to be validated using quantitative PCR. To our knowledge this will be the first genome-wide CNV analysis performed within a cohort of samples with SLI.

Poster presentation [pdf]