The Fine-Scale and Complex Architecture of Human Copy-Number Variation
| Autor: | Amir Ben-Dor, Jong Il Kim, Peter Tsang, George H. Perry, Stephen Laderman, Nick Sampas, Laia Rodriguez-Revenga, Charles W. Tran, Jeong-Sun Seo, Israel Steinfeld, Han Soo Park, Anya Tsalenko, Zohar Yakhini, N. Alice Yamada, Laurakay Bruhn, Charles Lee, Alicia F. Scheffer |
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| Rok vydání: | 2008 |
| Předmět: |
Gene Dosage
Biology Genome Article 03 medical and health sciences 0302 clinical medicine Genetic variation Genetics Humans Genetics(clinical) Copy-number variation International HapMap Project Genetics (clinical) Oligonucleotide Array Sequence Analysis 030304 developmental biology Genetic association 0303 health sciences Genome Human Genetic Variation Human genetics Tandem Repeat Sequences Evolutionary biology 030220 oncology & carcinogenesis Human genome Comparative genomic hybridization |
| Zdroj: | The American Journal of Human Genetics. 82(3):685-695 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2007.12.010 |
| Popis: | Despite considerable excitement over the potential functional significance of copy-number variants (CNVs), we still lack knowledge of the fine-scale architecture of the large majority of CNV regions in the human genome. In this study, we used a high-resolution array-based comparative genomic hybridization (aCGH) platform that targeted known CNV regions of the human genome at approximately 1 kb resolution to interrogate the genomic DNAs of 30 individuals from four HapMap populations. Our results revealed that 1020 of 1153 CNV loci (88%) were actually smaller in size than what is recorded in the Database of Genomic Variants based on previously published studies. A reduction in size of more than 50% was observed for 876 CNV regions (76%). We conclude that the total genomic content of currently known common human CNVs is likely smaller than previously thought. In addition, approximately 8% of the CNV regions observed in multiple individuals exhibited genomic architectural complexity in the form of smaller CNVs within larger ones and CNVs with interindividual variation in breakpoints. Future association studies that aim to capture the potential influences of CNVs on disease phenotypes will need to consider how to best ascertain this previously uncharacterized complexity. |
| Databáze: | OpenAIRE |
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