Open Access Highly Accessed Research article

Large-scale copy number variants (CNVs): Distribution in normal subjects and FISH/real-time qPCR analysis

Ying Qiao12, Xudong Liu3456, Chansonette Harvard12, Sarah L Nolin57, W Ted Brown57, Maryam Koochek24, Jeanette JA Holden34568, ME Suzanne Lewis256 and Evica Rajcan-Separovic156*

Author Affiliations

1 Department of Pathology, UBC, Children's and Women's Health Centre of BC, 4480 Oak Street, Vancouver, V6H 3V4, British Columbia, Canada

2 Department of Medical Genetics, UBC, Children's and Women's Health Center of BC C234, 4500 Oak Street, Vancouver, V6H 3N1, British Columbia, Canada

3 Department of Physiology, Queen's University, 191 Portsmouth Avenue, Kingston, K7M 8A6, Ontario, Canada

4 Autism Research Program, Ongwanada, 191 Portsmouth Avenue, Kingston, K7M 8A6, Ontario, Canada

5 Autism Spectrum Disorders – Canadian-American Research Consortium

6 Healthcare Equity for Intellectually Disabled Individuals (HEIDI) Research Program

7 Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA

8 Department of Psychiatry, Queen's University, 191 Portsmouth Avenue, Kingston, K7M 8A6, Ontario, Canada

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BMC Genomics 2007, 8:167  doi:10.1186/1471-2164-8-167

Published: 12 June 2007



Genomic copy number variants (CNVs) involving >1 kb of DNA have recently been found to be widely distributed throughout the human genome. They represent a newly recognized form of DNA variation in normal populations, discovered through screening of the human genome using high-throughput and high resolution methods such as array comparative genomic hybridization (array-CGH). In order to understand their potential significance and to facilitate interpretation of array-CGH findings in constitutional disorders and cancers, we studied 27 normal individuals (9 Caucasian; 9 African American; 9 Hispanic) using commercially available 1 Mb resolution BAC array (Spectral Genomics). A selection of CNVs was further analyzed by FISH and real-time quantitative PCR (RT-qPCR).


A total of 42 different CNVs were detected in 27 normal subjects. Sixteen (38%) were not previously reported. Thirteen of the 42 CNVs (31%) contained 28 genes listed in OMIM. FISH analysis of 6 CNVs (4 previously reported and 2 novel CNVs) in normal subjects resulted in the confirmation of copy number changes for 1 of 2 novel CNVs and 2 of 4 known CNVs. Three CNVs tested by FISH were further validated by RT-qPCR and comparable data were obtained. This included the lack of copy number change by both RT-qPCR and FISH for clone RP11-100C24, one of the most common known copy number variants, as well as confirmation of deletions for clones RP11-89M16 and RP5-1011O17.


We have described 16 novel CNVs in 27 individuals. Further study of a small selection of CNVs indicated concordant and discordant array vs. FISH/RT-qPCR results. Although a large number of CNVs has been reported to date, quantification using independent methods and detailed cellular and/or molecular assessment has been performed on a very small number of CNVs. This information is, however, very much needed as it is currently common practice to consider CNVs reported in normal subjects as benign changes when detected in individuals affected with a variety of developmental disorders.