High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

Butler, Merlin G.; Rafi, Syed K.; Manzardo, Ann M.

doi:10.3390/ijms16036464

Cited by 59 publications

(68 citation statements)

References 54 publications

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“…The original gene lists reported in the literature included 792 genes for ASD [21], 290 genes for bipolar disorder [22] and 560 genes for schizophrenia [23], and of these, 23 genes were found in common in all three conditions (see Table 1). Functional analysis of the 23 genes identified from the submitted list of genes showed a high match for schizophrenia (17 genes, score = 15.1) with medium-match scores representing 25 other disorders including bipolar disorder (nine genes, score = 9.6) and autism spectrum disorder (10 genes, score = 9.1).…”

Section: Resultsmentioning

confidence: 99%

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GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

Khanzada

Butler

Manzardo

2017

IJMS

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Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2). Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.

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Section: Resultsmentioning

confidence: 99%

“…Herein, we use the GeneAnalytics [20] program pathway analysis to further profile and characterize the underlying molecular architecture of clinically and etiologically relevant genes common to ASD [21], bipolar disorder [22] and schizophrenia [23] and associated diseases.…”

Section: Introductionmentioning

confidence: 99%

GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

Khanzada

Butler

Manzardo

2017

IJMS

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“…Iossifov et al [2012] reported a male with a missense mutation (c.1997 A>G) in the TOP3B gene who also had autism. Butler et al [2015] identified TOP3B as a clinically relevant gene in a review of genes involved with autism spectrum disorders. Tan et al [2011] reported a male with a deletion encompassing only a subset of the area deleted in our patient and including over half of the TOP3B gene; this patient had phenotypic similarities to our patient, including learning difficulties and delay in expressive language skills.…”

Section: Resultsmentioning

confidence: 99%

Deletion of <b><i>TOP3B</i></b> Is Associated with Cognitive Impairment and Facial Dysmorphism

Kaufman

Genovese

Butler³

2016

Cytogenet Genome Res

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Deletions of different regions of chromosome 22q11 have been extensively characterized in the literature, with a recent review outlining common deletions with a standardized system proposed for classification and nomenclature. The genotype-phenotype relationships have not been sufficiently elucidated for these deletions, and it remains unclear which specific genes play the dominant roles in producing associated clinical features. Several deletions involve entirely distinct regions of chromosome 22q11 but do not overlap, suggesting that a number of different genes contribute to the clinical features. Studies of patients with small deletions involving only 1 or 2 genes may provide more convincing evidence for the impact of individual genes on the observed phenotype. In this case report, we present a 12-year-old female with autism, cognitive impairment, dysmorphic features, and behavioral concerns and a 268-kb deletion of chromosome 22q11.22 including TOP3B, the only recognized disease-causing gene in the deletion. The mechanism of pathogenesis contributing significantly to our patient's clinical findings may relate to interaction between TOP3B and fragile X mental retardation protein (FMRP), an mRNA-binding protein that regulates translation and is altered in fragile X syndrome, a condition involving developmental delay, learning disability, and autism. All these features are recognized in our patient.

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“…Multiplex families and twin studies have shown that ASDs have a heritability as high as 90% [143,150,151]. This has led to a large number of genomic studies searching for the molecular etiology of ASD, which together have proposed 695 candidate genes [152] among them PCDH8, PCDHGA1, PCDHB15 [150], PCDH9 [146,153], PCDH10 [153,154], PCDH15 [155] , PCDHB4 [156], and the PCDHA gene cluster [157]. …”

Section: Roles In Behavior and Neurological Or Neurodevelopmental Dismentioning

confidence: 99%

Regulation of neural circuit formation by protocadherins

Peek

Mah

Weiner

2017

Cell. Mol. Life Sci.

114

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The Protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990's. Data implicating the Pcdhs, including ∼60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ∼10 non-clustered Pcdhs, in the regulation of neural development has continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination. We further discuss studies implicating mutation or epigenetic dysregulation of Pcdh genes in a variety of human neurodevelopmental and neurological disorders. With recent structural modeling of Pcdh proteins, the prospects for uncovering molecular mechanisms of Pcdh extracellular and intracellular interactions, and their role in normal and disrupted neural circuit formation, are bright.

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High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

Cited by 59 publications

References 54 publications

GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

Deletion of <b><i>TOP3B</i></b> Is Associated with Cognitive Impairment and Facial Dysmorphism

Regulation of neural circuit formation by protocadherins

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