Based on recent studies published by our group and others, it was discovered that large-scale DMA copy number variants invisible at the cytogenetic level (CNVs), are a ubiquitous characteristic of the human genome. Our findings indicated that, on average, two individuals differ by a dozen CNVs involving 3 Mb or approximately 0.1 % of the genome. This is comparable to the 0.1 % of genetic difference that is due to single nucleotide polymorphisms (SNPs). However, in contrast to nucleotide sequence variants such as SNPs, structural variation in the genome has not been well characterized. Much remains to be learned about the genomic locations, frequency, and stability of these structural variants and their importance in human evolution and genetic disease. To enable further research in this are it is necessary to expand the current knowledge of copy number variation by characterizing a large sample of individuals and constructing a database of validated CNVs. A comprehensive catalog of CNVs will facilitate large-scale studies of (1) the association of CNVs with disease risk (2) the effects of CNVs on response to drug treatment, and (3) the role of structural variation in human evolution. We propose to collect a data resource on genome copy number variation on 270 individuals from the international HapMap project using a powerful high-resolution CNV discovery method, Representational Oligonucleotide Microarray Analysis (ROMA). We will perform ROMA scans using a 380,000 probe array that provides a resolution of 8 kb. In addtion, we will integrate our data with CNV information obtain using other CNV discovery methods. We will select a set of 600 common CNVs (minor allele frequency >= 1%) for fine-scale characterization, and the boundaries of common CNVs will be defined at higher resolution using a tiling path Oligonucleotide array with a resolution of one probe every 5 bp. For a further subset of deletions and duplications, we will characterize the CNV junctions at the sequence level. Lastly, in order to integrate CNVs into the context the SNP-based HapMap, we will identify SNP markers that are in linkage disequilibrium with CNVs. All information on copy number variation will be made available through dbSNP and raw microarray data will be made available from www.hapmap.org . ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Biotechnology Resource Grants (P41)
Project #
1P41HG004222-01
Application #
7245358
Study Section
Special Emphasis Panel (ZHG1-HGR-M (J1))
Program Officer
Brooks, Lisa
Project Start
2007-05-15
Project End
2010-03-31
Budget Start
2007-05-15
Budget End
2008-03-31
Support Year
1
Fiscal Year
2007
Total Cost
$732,400
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
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