Distribution and functional impact of DNA copy number variation in the rat

Victor Guryev; Kathrin Saar; Tatjana Adamovic; Mark Verheul; Sebastiaan A A C van Heesch; Stuart Cook; Michal Pravenec; Timothy Aitman; Howard Jacob; James D Shull; Norbert Hubner; Edwin Cuppen

doi:10.1038/ng.141

Distribution and functional impact of DNA copy number variation in the rat

Victor Guryev, Kathrin Saar, Tatjana Adamovic, Mark Verheul, Sebastiaan A A C van Heesch, Stuart Cook, Michal Pravenec, Timothy Aitman, Howard Jacob, James D Shull, Norbert Hubner, Edwin Cuppen

Research output: Contribution to journal › Article › peer-review

Abstract

The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.

Original language	English
Pages (from-to)	538-45
Number of pages	8
Journal	Nature Genetics
Volume	40
Issue number	5
DOIs	https://doi.org/10.1038/ng.141
Publication status	Published - May 2008

Keywords / Materials (for Non-textual outputs)

Animals
Chromosomes
Computational Biology
DNA
Disease Models, Animal
Gene Expression
Genetic Diseases, Inborn
Genome
Humans
Nucleic Acid Hybridization
Quantitative Trait Loci
Rats
Rats, Inbred Strains

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10.1038/ng.141

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title = "Distribution and functional impact of DNA copy number variation in the rat",

abstract = "The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.",

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doi = "10.1038/ng.141",

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AU - Guryev, Victor

AU - Saar, Kathrin

AU - Adamovic, Tatjana

AU - Verheul, Mark

AU - van Heesch, Sebastiaan A A C

AU - Cook, Stuart

AU - Pravenec, Michal

AU - Aitman, Timothy

AU - Jacob, Howard

AU - Shull, James D

AU - Hubner, Norbert

AU - Cuppen, Edwin

PY - 2008/5

Y1 - 2008/5

N2 - The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.

AB - The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.

KW - Animals

KW - Chromosomes

KW - Computational Biology

KW - DNA

KW - Disease Models, Animal

KW - Gene Expression

KW - Genetic Diseases, Inborn

KW - Genome

KW - Humans

KW - Nucleic Acid Hybridization

KW - Quantitative Trait Loci

KW - Rats

KW - Rats, Inbred Strains

U2 - 10.1038/ng.141

DO - 10.1038/ng.141

M3 - Article

C2 - 18443591

SN - 1061-4036

VL - 40

SP - 538

EP - 545

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Distribution and functional impact of DNA copy number variation in the rat

Abstract

Keywords / Materials (for Non-textual outputs)

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