title: The fine-scale and complex architecture of human copy-number variation.
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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Perry
authors.forename: Amir
authors.initials: A
authors.lastname: Ben-Dor
authors.forename: Anya
authors.initials: A
authors.lastname: Tsalenko
authors.forename: Nick
authors.initials: N
authors.lastname: Sampas
authors.forename: Laia
authors.initials: L
authors.lastname: Rodriguez-Revenga
authors.forename: Charles W
authors.initials: CW
authors.lastname: Tran
authors.forename: Alicia
authors.initials: A
authors.lastname: Scheffer
authors.forename: Israel
authors.initials: I
authors.lastname: Steinfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Tsang
authors.forename: N Alice
authors.initials: NA
authors.lastname: Yamada
authors.forename: Han Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Stephen
authors.initials: S
authors.lastname: Laderman
authors.forename: Laurakay
authors.initials: L
authors.lastname: Bruhn
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
mesh_terms: D018628:Gene Dosage; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020080:Tandem Repeat Sequences