The Fine-scale and Complex Architecture of Human Copy-number Variation

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2008 Feb 29

PMID 18304495

Citations 175

Authors

George H Perry

Amir Ben-Dor

Anya Tsalenko

Nick Sampas

Laia Rodriguez-Revenga

Charles W Tran

Alicia Scheffer

Israel Steinfeld

Peter Tsang

N Alice Yamada

Han Soo Park

Jong-Il Kim

Jeong-Sun Seo

Zohar Yakhini

Stephen Laderman

Laurakay Bruhn

Charles Lee

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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