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- Stamouli, S, et al.
(författare)
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Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
- 2018
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 21:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood, and suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.
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- Arora, M., et al.
(författare)
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Fetal and postnatal metal dysregulation in autism
- 2017
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Ingår i: Nat Commun. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
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- Bolte, S., et al.
(författare)
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How can clinicians detect and treat autism early? Methodological trends of technology use in research
- 2016
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:2, s. 137-144
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Forskningsöversikt (refereegranskat)abstract
- We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965 to 2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye tracking were the most frequently used technologies. Conclusion: The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated, and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention.
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- Bolte, S., et al.
(författare)
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The Roots of Autism and ADHD Twin Study in Sweden (RATSS)
- 2014
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Ingår i: Twin Research and Human Genetics. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:3, s. 164-176
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Tidskriftsartikel (refereegranskat)abstract
- Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.
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