Human Molecular Genetics Advance Access originally published online on July 31, 2009
Human Molecular Genetics 2009 18(21):4118-4129; doi:10.1093/hmg/ddp360
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Copy number variation influences gene expression and metabolic traits in mice
1 Department of Human Genetics, UCLA, Los Angeles, CA, USA 2 Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA 3 Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
* To whom correspondence should be addressed. Tel: +1 3108251359; Fax: +1 3107947345; Email: LDOrozco{at}mednet.ucla.edu
Received March 19, 2009; Revised June 17, 2009; Accepted July 28, 2009
Copy number variants (CNVs) are genomic segments which are duplicated or deleted among different individuals. CNVs have been implicated in both Mendelian and complex traits, including immune and behavioral disorders, but the study of the mechanisms by which CNVs influence gene expression and clinical phenotypes in humans is complicated by the limited access to tissues and by population heterogeneity. We now report studies of the effect of 19 CNVs on gene expression and metabolic traits in a mouse intercross between strains C57BL/6J and C3H/HeJ. We found that 83% of genes predicted to occur within CNVs were differentially expressed. The expression of most CNV genes was correlated with copy number, but we also observed evidence that gene expression was altered in genes flanking CNVs, suggesting that CNVs may contain regulatory elements for these genes. Several CNVs mapped to hotspots, genomic regions influencing expression of tens or hundreds of genes. Several metabolic traits including cholesterol, triglycerides, glucose and body weight mapped to three CNVs in the genome, in mouse chromosomes 1, 4 and 17. Predicted CNV genes, such as Itlna, Defcr-1, Trim12 and Trim34 were highly correlated with these traits. Our results suggest that CNVs have a significant impact on gene expression and that CNVs may be playing a role in the mechanisms underlying metabolic traits in mice.