Amaia Carrión Castillo

Publications

Displaying 1 - 8 of 8
  • Carrion Castillo, A., Van der Haegen, L., Tzourio-Mazoyer, N., Kavaklioglu, T., Badillo, S., Chavent, M., Saracco, J., Brysbaert, M., Fisher, S. E., Mazoyer, B., & Francks, C. (2019). Genome sequencing for rightward hemispheric language dominance. Genes, Brain and Behavior. Advance online publication. doi:10.1111/gbb.12572.

    Abstract

    Most people have left‐hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic‐developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole‐genome‐sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. This was by analogy with situs inversus of the visceral organs (left‐right mirror reversal of the heart, lungs and so on), which is sometimes due to monogenic mutations. The genomes of 33 subjects with RHLD were sequenced and analyzed with reference to large population‐genetic data sets, as well as 34 subjects (14 left‐handed) with typical language laterality. The sample was powered to detect rare, highly penetrant, monogenic effects if they would be present in at least 10 of the 33 RHLD cases and no controls, but no individual genes had mutations in more than five RHLD cases while being un‐mutated in controls. A hypothesis derived from invertebrate mechanisms of left‐right axis formation led to the detection of an increased mutation load, in RHLD subjects, within genes involved with the actin cytoskeleton. The latter finding offers a first, tentative insight into molecular genetic influences on hemispheric language dominance.

    Supplementary material

    gbb12572-sup-0001-AppendixS1.docx
  • Eising, E., Carrion Castillo, A., Vino, A., Strand, E. A., Jakielski, K. J., Scerri, T. S., Hildebrand, M. S., Webster, R., Ma, A., Mazoyer, B., Francks, C., Bahlo, M., Scheffer, I. E., Morgan, A. T., Shriberg, L. D., & Fisher, S. E. (2019). A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development. Molecular Psychiatry, 24, 1065-1078. doi:10.1038/s41380-018-0020-x.

    Abstract

    Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5. In other probands, we identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to neurodevelopment. Several of the new candidates interact with each other or with known speech-related genes. Moreover, they show significant clustering within a single co-expression module of genes highly expressed during early human brain development. This study highlights gene regulatory pathways in the developing brain that may contribute to acquisition of proficient speech.

    Supplementary material

    Eising_etal_2018sup.pdf
  • De Kovel, C. G. F., Carrion Castillo, A., & Francks, C. (2019). A large-scale population study of early life factors influencing left-handedness. Scientific Reports, 9: 584. doi:10.1038/s41598-018-37423-8.

    Abstract

    Hand preference is a conspicuous variation in human behaviour, with a worldwide proportion of around 90% of people preferring to use the right hand for many tasks, and 10% the left hand. We used the large cohort of the UK biobank (~500,000 participants) to study possible relations between early life factors and adult hand preference. The probability of being left-handed was affected by the year and location of birth, likely due to cultural effects. In addition, hand preference was affected by birthweight, being part of a multiple birth, season of birth, breastfeeding, and sex, with each effect remaining significant after accounting for all others. Analysis of genome-wide genotype data showed that left-handedness was very weakly heritable, but shared no genetic basis with birthweight. Although on average left-handers and right-handers differed for a number of early life factors, all together these factors had only a minimal predictive value for individual hand preference.

    Supplementary material

    Supplementary information
  • Carrion Castillo, A., Maassen, B., Franke, B., Heister, A., Naber, M., Van der Leij, A., Francks, C., & Fisher, S. E. (2017). Association analysis of dyslexia candidate genes in a Dutch longitudinal sample. European Journal of Human Genetics, 25(4), 452-460. doi:10.1038/ejhg.2016.194.

    Abstract

    Dyslexia is a common specific learning disability with a substantive genetic component. Several candidate genes have been proposed to be implicated in dyslexia susceptibility, such as DYX1C1, ROBO1, KIAA0319, and DCDC2. Associations with variants in these genes have also been reported with a variety of psychometric measures tapping into the underlying processes that might be impaired in dyslexic people. In this study, we first conducted a literature review to select single nucleotide polymorphisms (SNPs) in dyslexia candidate genes that had been repeatedly implicated across studies. We then assessed the SNPs for association in the richly phenotyped longitudinal data set from the Dutch Dyslexia Program. We tested for association with several quantitative traits, including word and nonword reading fluency, rapid naming, phoneme deletion, and nonword repetition. In this, we took advantage of the longitudinal nature of the sample to examine if associations were stable across four educational time-points (from 7 to 12 years). Two SNPs in the KIAA0319 gene were nominally associated with rapid naming, and these associations were stable across different ages. Genetic association analysis with complex cognitive traits can be enriched through the use of longitudinal information on trait development.
  • Carrion Castillo, A., van Bergen, E., Vino, A., van Zuijen, T., de Jong, P. F., Francks, C., & Fisher, S. E. (2016). Evaluation of results from genome-wide studies of language and reading in a novel independent dataset. Genes, Brain and Behavior, 15(6), 531-541. doi:10.1111/gbb.12299.

    Abstract

    Recent genome wide association scans (GWAS) for reading and language abilities have pin-pointed promising new candidate loci. However, the potential contributions of these loci remain to be validated. In the present study, we tested 17 of the most significantly associated single nucleotide polymorphisms (SNPs) from these GWAS studies (p < 10−6 in the original studies) in a new independent population dataset from the Netherlands: known as FIOLA (Familial Influences On Literacy Abilities). This dataset comprised 483 children from 307 nuclear families, plus 505 adults (including parents of participating children), and provided adequate statistical power to detect the effects that were previously reported. The following measures of reading and language performance were collected: word reading fluency, nonword reading fluency, phonological awareness, and rapid automatized naming. Two SNPs (rs12636438, rs7187223) were associated with performance in multivariate and univariate testing, but these did not remain significant after correction for multiple testing. Another SNP (rs482700) was only nominally associated in the multivariate test. For the rest of the SNPs we did not find supportive evidence of association. The findings may reflect differences between our study and the previous investigations in respects such as the language of testing, the exact tests used, and the recruitment criteria. Alternatively, most of the prior reported associations may have been false positives. A larger scale GWAS meta-analysis than those previously performed will likely be required to obtain robust insights into the genomic architecture underlying reading and language.
  • Carrion Castillo, A. (2016). Deciphering common and rare genetic effects on reading ability. PhD Thesis, Radboud University Nijmegen, Nijmegen.
  • Agus, T., Carrion Castillo, A., Pressnitzer, D., & Ramus, F. (2014). Perceptual learning of acoustic noise by individuals with dyslexia. Journal of Speech, Language, and Hearing Research., 57, 1069-1077. doi:10.1044/1092-4388(2013/13-0020).

    Abstract

    Purpose: A phonological deficit is thought to affect most individuals with developmental dyslexia. The present study addresses whether the phonological deficit is caused by difficulties with perceptual learning of fine acoustic details. Method: A demanding test of nonverbal auditory memory, “noise learning,” was administered to both adults with dyslexia and control adult participants. On each trial, listeners had to decide whether a stimulus was a 1-s noise token or 2 abutting presentations of the same 0.5-s noise token (repeated noise). Without the listener’s knowledge, the exact same noise tokens were presented over many trials. An improved ability to perform the task for such “reference” noises reflects learning of their acoustic details. Results: Listeners with dyslexia did not differ from controls in any aspect of the task, qualitatively or quantitatively. They required the same amount of training to achieve discrimination of repeated from nonrepeated noises, and they learned the reference noises as often and as rapidly as the control group. However, they did show all the hallmarks of dyslexia, including a well-characterized phonological deficit. Conclusion: The data did not support the hypothesis that deficits in basic auditory processing or nonverbal learning and memory are the cause of the phonological deficit in dyslexia
  • Carrion Castillo, A., Franke, B., & Fisher, S. E. (2013). Molecular genetics of dyslexia: An overview. Dyslexia, 19(4), 214-240. doi:10.1002/dys.1464.

    Abstract

    Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlighted some intriguing mechanistic pathways, such as neuronal migration, axon guidance, and ciliary biology, but it is clear that we still have much to learn about the molecular networks that are involved. We end the review by highlighting the past, present, and future contributions of the Dutch Dyslexia Programme to studies of genetic factors. In particular, we emphasize the importance of relating genetic information to intermediate neurobiological measures, as well as the value of incorporating longitudinal and developmental data into molecular designs

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