Article

Copy number variation accuracy in genome-wide association studies.

Department of Psychiatry, Washington University, St. Louis, MO 63110, USA.
Human Heredity (impact factor: 1.79). 01/2011; 71(3):141-7. DOI:10.1159/000324683 pp.141-7
Source: PubMed

ABSTRACT Copy number variations (CNVs) are a major source of alterations among individuals and are a potential risk factor in many diseases. Numerous diseases have been linked to deletions and duplications of these chromosomal segments. Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned.
To help researchers reduce the number of false-positive CNVs that need to be followed up with laboratory testing, we evaluated the relative performance of CNVPartition, PennCNV and QuantiSNP, and developed a statistical method for estimating sensitivity and positive predictive values of CNV calls and tested it on 96 duplicate samples in our dataset.
We found that the positive predictive rate increases with the number of probes in the CNV and the size of the CNV, with the highest positive predicted rates in CNVs of at least 500 kb and at least 100 probes. Our analysis also indicates that identifying CNVs reported by multiple programs can greatly improve the reproducibility rate and the positive predicted rate.
Our methods can be used by investigators to identify CNVs in genome-wide data with greater reliability.

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    Article: Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability.
    Jacques S Beckmann, Xavier Estivill, Stylianos E Antonarakis
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    ABSTRACT: A considerable and unanticipated plasticity of the human genome, manifested as inter-individual copy number variation, has been discovered. These structural changes constitute a major source of inter-individual genetic variation that could explain variable penetrance of inherited (Mendelian and polygenic) diseases and variation in the phenotypic expression of aneuploidies and sporadic traits, and might represent a major factor in the aetiology of complex, multifactorial traits. For these reasons, an effort should be made to discover all common and rare copy number variants (CNVs) in the human population. This will also enable systematic exploration of both SNPs and CNVs in association studies to identify the genomic contributors to the common disorders and complex traits.
    Nature Reviews Genetics 09/2007; 8(8):639-46. · 38.08 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

96 duplicate samples
 
chromosomal segments
 
Copy number variations
 
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different computer programs
 
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multiple programs
 
Numerous diseases
 
positive predictive rate increases
 
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potential risk factor
 
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reproducibility rate
 
statistical method