Impact of constitutional copy number variants on biological pathway evolution

BMC Evolutionary Biology

Research Article

Mark A Rubin¹  Maria Poptsova¹  Francesca Demichelis²  Omer Gokcumen³  Samprit Banerjee⁴ 

[1] Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA;Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA;Centre for Integrative Biology, University of Trento, Trento, Italy;Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA;Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA;Department of Public Health, Weill Cornell Medical College, New York, NY, USA;

关键词: CNVs;    Pathways;    Pathway evolution;    Population genetics;    eQTL;   

DOI  :  10.1186/1471-2148-13-19

 received in 2012-06-22, accepted in 2013-01-18,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundInherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data.ResultsWe implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels.ConclusionsThe analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

【 授权许可】

Unknown   
© Poptsova et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.