Copy-number variation and association studies of human disease

@article{Mccarroll2007CopynumberVA,
  title={Copy-number variation and association studies of human disease},
  author={Steven Mccarroll and David M Altshuler},
  journal={Nature Genetics},
  year={2007},
  volume={39 Suppl 1},
  pages={S37-S42}
}
The central goal of human genetics is to understand the inherited basis of human variation in phenotypes, elucidating human physiology, evolution and disease. Rare mutations have been found underlying two thousand mendelian diseases; more recently, it has become possible to assess systematically the contribution of common SNPs to complex disease. The known role of copy-number alterations in sporadic genomic disorders, combined with emerging information about inherited copy-number variation… 
Copy Number Variations in the Human Genome: Potential Source for Individual Diversity and Disease Association Studies
TLDR
The current coverage of CNVs in the human genome already has exceeded that of SNPs and is still in-creasing, and these large-scale struc-tural variants will serve as powerful sources to help the understanding of human genetic variation and of differences in disease susceptibility for various diseases.
Copy number variation and susceptibility to human disorders (Review).
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  • 2009
TLDR
Current knowledge regarding CNVs and their heritability is still rudimentary, due to their location in regions of complex genomic structure and to the technical limitations of association studies, but future advances in the technology will aid in the construction of a new CNV map.
Copy-number variation in control population cohorts.
TLDR
An example of how to discover new CNVs from existing genotype data from large-scale genetic epidemiological studies is provided and the need to expand surveys of CNV in different population-based cohorts and to apply the information to studies of human variation and disease is discussed.
Copy number variations and cancer
TLDR
A detailed overview of the current understanding of the CNVs that arise in the human genome is provided and the emerging literature that reveals associations of both constitutional and somatic CNVs with a wide variety of human cancers is explored.
Novel Association Strategy with Copy Number Variation for Identifying New Risk Loci of Human Diseases
TLDR
The results demonstrated the effectiveness and robustness of the CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases.
Copy Number Variations in Adult-onset Neuropsychiatric Diseases
TLDR
The CHRFAM7A human-specific fusion gene association warrants large scale locus specific association studies in AD, schizophrenia, bipolar disorder and ADHD and further large-scale studies with genotyping assays optimized for CNV detection are needed.
Copy number variations and cancer susceptibility
TLDR
The role of CNVs in cancer has only emerged in the last 2 years, with constitutional CNVs originally being observed in the Li-Fraumeni cancer susceptibility syndrome, and more recently in neuroblastoma.
Clinical implications of copy number variations in autoimmune disorders
TLDR
Evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases, but many findings need to be replicated in independent populations and different ethnic groups.
Genome-wide association study of copy number variation in 16,000 cases of eight common diseases and 3,000 shared controls
TLDR
A large, direct genome-wide study of association between CNVs and eight common human diseases concludes that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis ofcommon human diseases.
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References

SHOWING 1-10 OF 46 REFERENCES
Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes
TLDR
To determine the overall contribution of CNVs to complex phenotypes, association analyses of expression levels with SNPs and CNVs in individuals who are part of the International HapMap project show little overlap between the two types of variation.
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.
Common deletions and SNPs are in linkage disequilibrium in the human genome
TLDR
It is shown that common deletions and SNPs ascertained with similar criteria have essentially the same distribution of linkage disequilibrium with surrounding SNPs, indicating that these polymorphisms may share evolutionary history and that most deletion polymorphisms are effectively assayed by proxy in SNP-based association studies.
Completing the map of human genetic variation
TLDR
A community resource project recently launched by the National Human Genome Research Institute to sequence large-insert clones from many individuals, systematically discovering and resolving these complex variants at the DNA sequence level is described.
Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome
TLDR
A novel tool named eFISH (electronic fluorescence in situ hybridization) is described, a BLAST-based program that was developed to facilitate the choice of appropriate clones for FISH and CGH experiments, as well as interpretation of results in which genomic DNA probes are used in hybridization-based experiments.
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.
A haplotype map of the human genome
TLDR
A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
A haplotype map of the human genome.
TLDR
A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
Common deletion polymorphisms in the human genome
TLDR
This work describes a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome.
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