scholarly journals Animal Models of Psychiatric Disorders That Reflect Human Copy Number Variation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jun Nomura ◽  
Toru Takumi
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Copy Number ◽  
Chromosome Rearrangement ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Large Chromosome ◽  
Brain Anatomy ◽  
Normal Brain ◽  
Chromosome Engineering

The development of genetic technologies has led to the identification of several copy number variations (CNVs) in the human genome. Genome rearrangements affect dosage-sensitive gene expression in normal brain development. There is strong evidence associating human psychiatric disorders, especially autism spectrum disorders (ASDs) and schizophrenia to genetic risk factors and accumulated CNV risk loci. Deletions in 1q21, 3q29, 15q13, 17p12, and 22q11, as well as duplications in 16p11, 16p13, and 15q11-13 have been reported as recurrent CNVs in ASD and/or schizophrenia. Chromosome engineering can be a useful technology to reflect human diseases in animal models, especially CNV-based psychiatric disorders. This system, based on the Cre/loxPstrategy, uses large chromosome rearrangement such as deletion, duplication, inversion, and translocation. Although it is hard to reflect human pathophysiology in animal models, some aspects of molecular pathways, brain anatomy, cognitive, and behavioral phenotypes can be addressed. Some groups have created animal models of psychiatric disorders, ASD, and schizophrenia, which are based on human CNV. These mouse models display some brain anatomical and behavioral abnormalities, providing insight into human neuropsychiatric disorders that will contribute to novel drug screening for these devastating disorders.

scholarly journals Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Kyleen Luhrs ◽  
Tracey Ward ◽  
Caitlin M. Hudac ◽  
Jennifer Gerdts ◽  
Holly A. F. Stessman ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Copy Number ◽  
Depressive Disorders ◽  
De Novo ◽  
Familial Risk ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genetic Etiology ◽  
Additive Contribution ◽  
Familial Risk Factors

The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD) with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62), de novo deletion copy number variations (DEL, n=74), de novo likely gene-disrupting mutations (LGDM, n=267), and children without a known genetic etiology (NON, n=2111). Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

scholarly journals Modeling and Predicting Developmental Trajectories of Neuropsychiatric Dimensions Associated With Copy Number Variations

2019 ◽  
Vol 22 (8) ◽  
pp. 488-500 ◽  
Author(s):  
Noboru Hiroi ◽  
Takahira Yamauchi
Keyword(s):  
Autism Spectrum Disorder ◽  
Working Memory ◽  
Psychiatric Disorders ◽  
Mouse Models ◽  
Social Communication ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Spectrum Disorder ◽  
Catecholamine Metabolism

AbstractCopy number variants, such as duplications and hemizygous deletions at chromosomal loci of up to a few million base pairs, are highly associated with psychiatric disorders. Hemizygous deletions at human chromosome 22q11.2 were found to be associated with elevated instances of schizophrenia and autism spectrum disorder in 1992 and 2002, respectively. Following these discoveries, many mouse models have been developed and tested to analyze the effects of gene dose alterations in small chromosomal segments and single genes of 22q11.2. Despite several limitations to modeling mental illness in mice, mouse models have identified several genes on 22q11.2—Tbx1, Dgcr8, Comt, Sept5, and Prodh—that contribute to dimensions of autism spectrum disorder and schizophrenia, including working memory, social communication and interaction, and sensorimotor gating. Mouse studies have identified that heterozygous deletion of Tbx1 results in defective social communication during the neonatal period and social interaction deficits during adolescence/adulthood. Overexpression of Tbx1 or Comt in adult neural progenitor cells in the hippocampus delays the developmental maturation of working memory capacity. Collectively, mouse models of variants of these 4 genes have revealed several potential neuronal mechanisms underlying various aspects of psychiatric disorders, including adult neurogenesis, microRNA processing, catecholamine metabolism, and synaptic transmission. The validity of the mouse data would be ultimately tested when therapies or drugs based on such potential mechanisms are applied to humans.

scholarly journals The Superior Visual Perception Hypothesis: Neuroaesthetics of Cave Art

2021 ◽  
Vol 11 (6) ◽  
pp. 81
Author(s):  
Per Olav Folgerø ◽  
Christer Johansson ◽  
Linn Heidi Stokkedal
Keyword(s):  
Visual Perception ◽  
Animal Movement ◽  
Homo Sapiens ◽  
Autism Spectrum ◽  
Modern Technology ◽  
Upper Paleolithic ◽  
Brain Anatomy ◽  
Normal Brain ◽  
Top Down ◽  
Cave Art

Cave Art in the Upper Paleolithic presents a boost of creativity and visual thinking. What can explain these savant-like paintings? The normal brain function in modern man rarely supports the creation of highly detailed paintings, particularly the convincing representation of animal movement, without extensive training and access to modern technology. Differences in neuro-signaling and brain anatomy between modern and archaic Homo sapiens could also cause differences in perception. The brain of archaic Homo sapiens could perceive raw detailed information without using pre-established top-down concepts, as opposed to the common understanding of the normal modern non-savant brain driven by top-down control. Some ancient genes preserved in modern humans may be expressed in rare disorders. Researchers have compared Cave Art with art made by people with autism spectrum disorder. We propose that archaic primary consciousness, as opposed to modern secondary consciousness, included a savant-like perception with a superior richness of details compared to modern man. Modern people with high frequencies of Neanderthal genes, have notable anatomical features such as increased skull width in the occipital and parietal visual areas. We hypothesize that the anatomical differences are functional and may allow a different path to visual perception.

scholarly journals Rare Copy Number Variations in a Chinese Cohort of Autism Spectrum Disorder

2018 ◽  
Vol 9 ◽  
Author(s):  
Yanjie Fan ◽  
Xiujuan Du ◽  
Xin Liu ◽  
Lili Wang ◽  
Fei Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Spectrum Disorder ◽  
Chinese Cohort

scholarly journals Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Olafur O. Gudmundsson ◽  
G. Bragi Walters ◽  
Andres Ingason ◽  
Stefan Johansson ◽  
Tetyana Zayats ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Neurodevelopmental Disorder ◽  
Copy Number Variant ◽  
Pleiotropic Effect ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Hyperactivity Disorder

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.

scholarly journals A large data resource of genomic copy number variation across neurodevelopmental disorders

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Mehdi Zarrei ◽  
Christie L. Burton ◽  
Worrawat Engchuan ◽  
Edwin J. Young ◽  
Edward J. Higginbotham ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Population Control ◽  
Large Data ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genomic Disorder ◽  
Rare Cnvs ◽  
Data Resource ◽  
Compulsive Disorder

Abstract Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

scholarly journals A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder

2012 ◽  
Vol 2 (12) ◽  
pp. 1665-1685 ◽  
Author(s):  
Aparna Prasad ◽  
Daniele Merico ◽  
Bhooma Thiruvahindrapuram ◽  
John Wei ◽  
Anath C. Lionel ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Spectrum Disorder

Recurrent copy number variations as risk factors for autism spectrum disorders: analysis of the clinical implications

2016 ◽  
Vol 89 (6) ◽  
pp. 708-718 ◽  
Author(s):  
V. Oikonomakis ◽  
K. Kosma ◽  
A. Mitrakos ◽  
C. Sofocleous ◽  
P. Pervanidou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Autism Spectrum Disorders ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Clinical Implications ◽  
Spectrum Disorders

scholarly journals Role of Copy Number Variations in ADHD

2020 ◽  
Author(s):  
Danijela Krgović
Keyword(s):  
Autism Spectrum Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Spectrum Disorder ◽  
Genetic Diagnostics ◽  
Healthy Controls

Copy number variations (CNV) have an important role in etiology of neurodevelopmental disorders (NDD). Among them, individuals with attention-deficit and hyperactivity disorders (ADHD) have 1.33 times higher overall rate of CNVs larger than 100 kb compared to healthy controls. These CNVs are often shared with other NDDs and neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD), although duplications of 15q13.3 and 16p13.11 have been found enriched in ADHD cohorts. CNVs provide new opportunities for studying and management of psychiatric disorders including ADHD. Therefore this chapter provides a brief overview of the literature on this topic and presents the benefits of CNV genetic diagnostics in ADHD patients.

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