Copy-number variations associated with neuropsychiatric conditions

@article{Cook2008CopynumberVA,
  title={Copy-number variations associated with neuropsychiatric conditions},
  author={Edwin H. Cook and Stephen W. Scherer},
  journal={Nature},
  year={2008},
  volume={455},
  pages={919-923}
}
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… 

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References

SHOWING 1-10 OF 58 REFERENCES
Genomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders
TLDR
It is speculated that CNV could underlie a significant proportion of normal human variation including differences in cognitive, behavioral, and psychological features.
Increase in GSK3β gene copy number variation in bipolar disorder
  • H. Lachman, Erika Pedrosa, +5 authors P. Stopkova
  • Biology, Medicine
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2007
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
Findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.
...
1
2
3
4
5
...