Genomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders

@article{Lee2006GenomicRA,
  title={Genomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders},
  author={Jennifer A. Lee and James R. Lupski},
  journal={Neuron},
  year={2006},
  volume={52},
  pages={103-121}
}
Genomic disorders are a group of human genetic diseases caused by genomic rearrangements resulting in copy-number variation (CNV) affecting a dosage-sensitive gene or genes critical for normal development or maintenance. These disorders represent a wide range of clinically distinct entities but include many diseases affecting nervous system function. Herein, we review selected neurodevelopmental, neurodegenerative, and psychiatric disorders either known or suggested to be caused by genomic… 
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TLDR
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TLDR
Since many human CNVs contain genes, the expression differences associated with these genes are very likely to influence normal phenotypic variation and at least some of them are expected to alter drug metabolism or to influence disease predisposition.
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TLDR
This chapter summarizes the known CNVs associated with human neurodevelopmental disorders and discusses how epigenetic mechanisms play a role in regulating genes implicated in these loci, and discusses the epigenetic layer of DNA methylation and its potential role in breakpoint instability in recent primate evolution.
Complex human chromosomal and genomic rearrangements.
Copy number variation (CNV) is a major source of genetic variation among humans. In addition to existing as benign polymorphisms, CNVs can also convey clinical phenotypes, including genomic
Role of Copy-Number Variations in Non-Coding Regions of Autism Spectrum Disorders
TLDR
It is found that Autism Spectrum Disorder specific copy-number variations were enriched in the non-coding regions, especially in the enhancer regions, and 19 novel functional cisregulatory enhancers in Autism Spectrum Disorders were identified.
Copy-number variation and association studies of human disease
TLDR
Evidence that CNVs affect phenotypes is discussed, directions for basic knowledge to support clinical study of CNVs, the challenge of genotyping CNPs in clinical cohorts, the use of SNPs as markers for CNPs and statistical challenges in testing CNVs for association with disease are discussed.
Copy number variants, diseases and gene expression.
TLDR
Initial evidence is described which revealed that genes in CNV regions are expressed at lower and more variable levels than genes mapping elsewhere, and also that CNV not only affects the expression of genes varying in copy number, but also has a global influence on the transcriptome.
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References

SHOWING 1-10 OF 254 REFERENCES
Genome architecture, rearrangements and genomic disorders.
TLDR
An increasing number of human diseases are recognized to result from recurrent DNA rearrangements involving unstable genomic regions, in which the clinical phenotype is a consequence of abnormal dosage of gene(s) located within the rearranged genomes.
Genomic Disorders: Molecular Mechanisms for Rearrangements and Conveyed Phenotypes
TLDR
The analyses of chromosome breakpoints in the proximal short arm of Chromosome 17 (17p) reveal nonallelic homologous recombination (NAHR) as a major mechanism for recurrent rearrangement whereas nonhomologous end-joining (NHEJ) can be responsible for many of the nonrecurrent rearrangements.
Copy number variation: new insights in genome diversity.
TLDR
Current efforts are directed toward a more comprehensive cataloging and characterization of CNVs that will provide the basis for determining how genomic diversity impacts biological function, evolution, and common human diseases.
Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits.
  • J. Lupski
  • Biology, Medicine
    Trends in genetics : TIG
  • 1998
TLDR
The advances of the human genome project and the completion of total genome sequences for yeast and many bacterial species, have enabled investigators to view genetic information in the context of the entire genome and recognize that the mechanisms for some genetic diseases are best understood at a genomic level.
DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling.
TLDR
Post-mortem brain DNA from bipolar disorder cases, schizophrenia cases and control individuals is screened for DNA copy-number aberrations and aberrant loci are reported, which may reveal insights into the etiology and genetic risk factors for these complex psychiatric disorders.
Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males
TLDR
The collective data suggest that increased MECP2 gene copy number is mainly responsible for the neurodevelopmental phenotypes in these males and underscores the value of molecular analysis for patient diagnosis, family members at risk, and genetic counseling.
Global variation in copy number in the human genome
TLDR
A first-generation CNV map of the human genome is constructed through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia, underscoring the importance of CNV in genetic diversity and evolution and the utility of this resource for genetic disease studies.
A Polymorphic Genomic Duplication on Human Chromosome 15 Is a Susceptibility Factor for Panic and Phobic Disorders
TLDR
An interstitial duplication of human chromosome 15q24-26 (named DUP25), which is significantly associated with panic/agoraphobia/social phobia/joint laxity in families, and with panic disorder in nonfamilial cases is identified.
Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome.
TLDR
A combination of BAC-based and high-density customized oligonucleotide arrays were used to resolve the molecular basis of structural rearrangements and underscore the need for complete maps of genetic variation in duplication-rich regions of the genome.
Genomic disorders on 22q11.
TLDR
Analysis of both the genomic sequence for the 22q11 interval and the orthologous regions in the mouse has identified >24 genes that are shared between VCFS/DGS and der(22) syndrome and has identified 14 putative genes that will help in the identification of candidate genes in these three syndromes.
...
1
2
3
4
5
...