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Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle

Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp–773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the db...

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Autores principales: Mesbah-Uddin, Md, Guldbrandtsen, Bernt, Iso-Touru, Terhi, Vilkki, Johanna, De Koning, Dirk-Jan, Boichard, Didier, Lund, Mogens Sandø, Sahana, Goutam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824824/
https://www.ncbi.nlm.nih.gov/pubmed/28985340
http://dx.doi.org/10.1093/dnares/dsx037
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author Mesbah-Uddin, Md
Guldbrandtsen, Bernt
Iso-Touru, Terhi
Vilkki, Johanna
De Koning, Dirk-Jan
Boichard, Didier
Lund, Mogens Sandø
Sahana, Goutam
author_facet Mesbah-Uddin, Md
Guldbrandtsen, Bernt
Iso-Touru, Terhi
Vilkki, Johanna
De Koning, Dirk-Jan
Boichard, Didier
Lund, Mogens Sandø
Sahana, Goutam
author_sort Mesbah-Uddin, Md
collection PubMed
description Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp–773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the dbVar database. Breakpoint sequence analyses revealed that majority (24 of 29 tested) of the deletions contain microhomology/homology at breakpoint, and therefore, most likely generated by microhomology-mediated end joining. We observed higher differentiation among breeds for deletions in some genic-regions, such as ABCA12, TTC1, VWA3B, TSHR, DST/BPAG1, and CD1D. The genes overlapping deletions are on average evolutionarily less conserved compared with known mouse lethal genes (P-value = 2.3 × 10(−6)). We report 167 natural gene knockouts in cattle that are apparently nonessential as live homozygote individuals are observed. These genes are functionally enriched for immunoglobulin domains, olfactory receptors, and MHC classes (FDR = 2.06 × 10(−22), 2.06 × 10(−22), 7.01 × 10(−6), respectively). We also demonstrate that deletions are enriched for health and fertility related quantitative trait loci (2-and 1.5-fold enrichment, Fisher’s P-value = 8.91 × 10(−10) and 7.4 × 10(−11), respectively). Finally, we identified and confirmed the breakpoint of a ∼525 KB deletion on Chr23:12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8), causing stillbirth in Nordic Red Cattle.
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spelling pubmed-58248242018-02-28 Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle Mesbah-Uddin, Md Guldbrandtsen, Bernt Iso-Touru, Terhi Vilkki, Johanna De Koning, Dirk-Jan Boichard, Didier Lund, Mogens Sandø Sahana, Goutam DNA Res Full Papers Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp–773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the dbVar database. Breakpoint sequence analyses revealed that majority (24 of 29 tested) of the deletions contain microhomology/homology at breakpoint, and therefore, most likely generated by microhomology-mediated end joining. We observed higher differentiation among breeds for deletions in some genic-regions, such as ABCA12, TTC1, VWA3B, TSHR, DST/BPAG1, and CD1D. The genes overlapping deletions are on average evolutionarily less conserved compared with known mouse lethal genes (P-value = 2.3 × 10(−6)). We report 167 natural gene knockouts in cattle that are apparently nonessential as live homozygote individuals are observed. These genes are functionally enriched for immunoglobulin domains, olfactory receptors, and MHC classes (FDR = 2.06 × 10(−22), 2.06 × 10(−22), 7.01 × 10(−6), respectively). We also demonstrate that deletions are enriched for health and fertility related quantitative trait loci (2-and 1.5-fold enrichment, Fisher’s P-value = 8.91 × 10(−10) and 7.4 × 10(−11), respectively). Finally, we identified and confirmed the breakpoint of a ∼525 KB deletion on Chr23:12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8), causing stillbirth in Nordic Red Cattle. Oxford University Press 2018-02 2017-09-08 /pmc/articles/PMC5824824/ /pubmed/28985340 http://dx.doi.org/10.1093/dnares/dsx037 Text en © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Full Papers
Mesbah-Uddin, Md
Guldbrandtsen, Bernt
Iso-Touru, Terhi
Vilkki, Johanna
De Koning, Dirk-Jan
Boichard, Didier
Lund, Mogens Sandø
Sahana, Goutam
Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
title Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
title_full Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
title_fullStr Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
title_full_unstemmed Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
title_short Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
title_sort genome-wide mapping of large deletions and their population-genetic properties in dairy cattle
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824824/
https://www.ncbi.nlm.nih.gov/pubmed/28985340
http://dx.doi.org/10.1093/dnares/dsx037
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