Novel origins of copy number variation in the dog genome.

Jonas Berglund, Elisa Nevalainen, Anna- Maja Molin, Michele Perloski, LUPA consortium, Catherine Andre, Michael C. Zody, Ted Sharpe, Christophe Hitte, Kerstin Lindblad-Toh, Hannes Tapani Lohi, Matt Webster

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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, that 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. 98% of CNVs observed in each breed 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.
Alkuperäiskielienglanti
LehtiGenome Biology
Vuosikerta13
Numero8
SivutR73
Sivumäärä41
ISSN1474-7596
DOI - pysyväislinkit
TilaJulkaistu - 2012
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 1184 Genetiikka, kehitysbiologia, fysiologia
  • 3111 Biolääketieteet

Lainaa tätä

Berglund, J., Nevalainen, E., Molin, A. M., Perloski, M., LUPA consortium, Andre, C., ... Webster, M. (2012). Novel origins of copy number variation in the dog genome. Genome Biology, 13(8), R73. https://doi.org/10.1186/gb-2012-13-8-r73
Berglund, Jonas ; Nevalainen, Elisa ; Molin, Anna- Maja ; Perloski, Michele ; LUPA consortium ; Andre, Catherine ; Zody, Michael C. ; Sharpe, Ted ; Hitte, Christophe ; Lindblad-Toh, Kerstin ; Lohi, Hannes Tapani ; Webster, Matt. / Novel origins of copy number variation in the dog genome. Julkaisussa: Genome Biology. 2012 ; Vuosikerta 13, Nro 8. Sivut R73.
@article{01c167b52924453980f68346ffeba0d0,
title = "Novel origins of copy number variation in the dog genome.",
abstract = "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, that 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. 98{\%} of CNVs observed in each breed 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.",
keywords = "1184 Genetics, developmental biology, physiology, 3111 Biomedicine",
author = "Jonas Berglund and Elisa Nevalainen and Molin, {Anna- Maja} and Michele Perloski and {LUPA consortium} and Catherine Andre and Zody, {Michael C.} and Ted Sharpe and Christophe Hitte and Kerstin Lindblad-Toh and Lohi, {Hannes Tapani} and Matt Webster",
year = "2012",
doi = "10.1186/gb-2012-13-8-r73",
language = "English",
volume = "13",
pages = "R73",
journal = "Genome Biology",
issn = "1474-7596",
publisher = "BioMed Central Ltd",
number = "8",

}

Berglund, J, Nevalainen, E, Molin, AM, Perloski, M, LUPA consortium, Andre, C, Zody, MC, Sharpe, T, Hitte, C, Lindblad-Toh, K, Lohi, HT & Webster, M 2012, 'Novel origins of copy number variation in the dog genome.' Genome Biology, Vuosikerta 13, Nro 8, Sivut R73. https://doi.org/10.1186/gb-2012-13-8-r73

Novel origins of copy number variation in the dog genome. / Berglund, Jonas; Nevalainen, Elisa; Molin, Anna- Maja; Perloski, Michele; LUPA consortium; Andre, Catherine; Zody, Michael C.; Sharpe, Ted; Hitte, Christophe; Lindblad-Toh, Kerstin; Lohi, Hannes Tapani; Webster, Matt.

julkaisussa: Genome Biology, Vuosikerta 13, Nro 8, 2012, s. R73.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Novel origins of copy number variation in the dog genome.

AU - Berglund, Jonas

AU - Nevalainen, Elisa

AU - Molin, Anna- Maja

AU - Perloski, Michele

AU - LUPA consortium

AU - Andre, Catherine

AU - Zody, Michael C.

AU - Sharpe, Ted

AU - Hitte, Christophe

AU - Lindblad-Toh, Kerstin

AU - Lohi, Hannes Tapani

AU - Webster, Matt

PY - 2012

Y1 - 2012

N2 - 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, that 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. 98% of CNVs observed in each breed 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.

AB - 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, that 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. 98% of CNVs observed in each breed 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.

KW - 1184 Genetics, developmental biology, physiology

KW - 3111 Biomedicine

U2 - 10.1186/gb-2012-13-8-r73

DO - 10.1186/gb-2012-13-8-r73

M3 - Article

VL - 13

SP - R73

JO - Genome Biology

JF - Genome Biology

SN - 1474-7596

IS - 8

ER -

Berglund J, Nevalainen E, Molin AM, Perloski M, LUPA consortium, Andre C et al. Novel origins of copy number variation in the dog genome. Genome Biology. 2012;13(8):R73. https://doi.org/10.1186/gb-2012-13-8-r73