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Novel origins of copy number variation in the dog genome
BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 g...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053742/ https://www.ncbi.nlm.nih.gov/pubmed/22916802 http://dx.doi.org/10.1186/gb-2012-13-8-r73 |
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author | Berglund, Jonas Nevalainen, Elisa M Molin, Anna-Maja Perloski, Michele André, Catherine Zody, Michael C Sharpe, Ted Hitte, Christophe Lindblad-Toh, Kerstin Lohi, Hannes Webster, Matthew T |
author_facet | Berglund, Jonas Nevalainen, Elisa M Molin, Anna-Maja Perloski, Michele André, Catherine Zody, Michael C Sharpe, Ted Hitte, Christophe Lindblad-Toh, Kerstin Lohi, Hannes Webster, Matthew T |
author_sort | Berglund, Jonas |
collection | PubMed |
description | BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution. |
format | Online Article Text |
id | pubmed-4053742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40537422014-06-13 Novel origins of copy number variation in the dog genome Berglund, Jonas Nevalainen, Elisa M Molin, Anna-Maja Perloski, Michele André, Catherine Zody, Michael C Sharpe, Ted Hitte, Christophe Lindblad-Toh, Kerstin Lohi, Hannes Webster, Matthew T Genome Biol Research BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution. BioMed Central 2012 2012-08-23 /pmc/articles/PMC4053742/ /pubmed/22916802 http://dx.doi.org/10.1186/gb-2012-13-8-r73 Text en Copyright © 2012 Berglund et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Research Berglund, Jonas Nevalainen, Elisa M Molin, Anna-Maja Perloski, Michele André, Catherine Zody, Michael C Sharpe, Ted Hitte, Christophe Lindblad-Toh, Kerstin Lohi, Hannes Webster, Matthew T Novel origins of copy number variation in the dog genome |
title | Novel origins of copy number variation in the dog genome |
title_full | Novel origins of copy number variation in the dog genome |
title_fullStr | Novel origins of copy number variation in the dog genome |
title_full_unstemmed | Novel origins of copy number variation in the dog genome |
title_short | Novel origins of copy number variation in the dog genome |
title_sort | novel origins of copy number variation in the dog genome |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053742/ https://www.ncbi.nlm.nih.gov/pubmed/22916802 http://dx.doi.org/10.1186/gb-2012-13-8-r73 |
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