Copy-number variations associated with neuropsychiatric conditions

  title={Copy-number variations associated with neuropsychiatric conditions},
  author={Edwin H. Cook and Stephen W. Scherer},
Neuropsychiatric conditions such as autism and schizophrenia have long been attributed to genetic alterations, but identifying the genes responsible has proved challenging. Microarray experiments have now revealed abundant copy-number variation — a type of variation in which stretches of DNA are duplicated, deleted and sometimes rearranged — in the human population. Genes affected by copy-number variation are good candidates for research into disease susceptibility. The complexity of… 

Genomic copy number variation in disorders of cognitive development.

  • E. Morrow
  • Psychology, Medicine
    Journal of the American Academy of Child and Adolescent Psychiatry
  • 2010

Phenotypic variations on the theme of CNVs

The highly pleiotropic effects observed for specific copy number variants (CNVs) challenge current classification of these disorders, but also provide opportunities to understand their origins and the relationships between them.

Human genome variation in health and in neuropsychiatric disorders.

Genome dynamics, including changes in gene number and position as well as epigenetic modifications of coding and noncoding sequences, can affect regulation of gene expression and may contribute to the variability of complex phenotypes.

Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems

The results from this study, the largest genotype-first analysis of schizophrenia susceptibility loci to date, suggest that the phenotypic effects of copy number variants associated with schizophrenia are pleiotropic and imply the existence of shared biologic pathways among multiple neurodevelopmental conditions.

Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia

These data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated with schizophrenia, as well as for common CNVs that may act as susceptibility factors by disturbing glutathione metabolism.

Copy number variations in schizophrenia: critical review and new perspectives on concepts of genetics and disease.

These initial genome-wide studies of CNVs provide replicated associations of schizophrenia with rare 1q21.1 and 15q13.3 deletions and point to a more general mutational mechanism involving rare CNVs that elevate risk for schizophrenia, especially more developmental forms of the disease.



Increase in GSK3β gene copy number variation in bipolar disorder

  • H. LachmanErika Pedrosa P. Stopkova
  • Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2007
Patients with BD have an increased frequency of this CNV—primarily the duplication variant—compared with controls, which suggests that GSK3β may be involved in BD susceptibility in some individuals and that CNVs in this and other candidate genes for psychiatric disorders should be analyzed as causative functional genetic variants.

Advances in autism genetics: on the threshold of a new neurobiology

Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme.

Rare chromosomal deletions and duplications increase risk of schizophrenia

A genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls provides strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.

Psychiatric genetics: progress amid controversy

More attention on unique families, rare variants, and on incorporating environment and the emerging knowledge of biological function and pathways into genetic analysis is warranted.

Large recurrent microdeletions associated with schizophrenia

In a genome-wide search for CNVs associating with schizophrenia, a population-based sample was used to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring and three deletions significantly associate with schizophrenia and related psychoses in the combined sample.

Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia

The results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia, and disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Linkage and copy number variation analyses implicate chromosome 11p12–p13 and neurexins, respectively, among other candidate loci, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Strong association of de novo copy number mutations with sporadic schizophrenia

The results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.

Strong Association of De Novo Copy Number Mutations with Autism

Findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.