The genetic consequences of dog breed formation - Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels
(2021) In PLoS Genetics 17(9). p.1-34- Abstract
Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents... (More)
Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.
(Less)
- author
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- in
- PLoS Genetics
- volume
- 17
- issue
- 9
- article number
- e1009726
- pages
- 1 - 34
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:34473707
- scopus:85114433751
- ISSN
- 1553-7390
- DOI
- 10.1371/journal.pgen.1009726
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2021 Axelsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- id
- f530a3ba-33a6-4655-bdb3-9023b8fa8606
- date added to LUP
- 2021-12-21 12:49:06
- date last changed
- 2024-04-20 18:11:35
@article{f530a3ba-33a6-4655-bdb3-9023b8fa8606,
abstract = {{<p>Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity. </p>}},
author = {{Axelsson, Erik and Ljungvall, Ingrid and Bhoumik, Priyasma and Conn, Laura Bas and Muren, Eva and Ohlsson, Åsa and Olsen, Lisbeth Høier and Engdahl, Karolina and Hagman, Ragnvi and Hanson, Jeanette and Kryvokhyzha, Dmytro and Pettersson, Mats and Grenet, Olivier and Moggs, Jonathan and Del Rio-Espinola, Alberto and Epe, Christian and Taillon, Bruce and Tawari, Nilesh and Mane, Shrinivas and Hawkins, Troy and Hedhammar, Åke and Gruet, Philippe and Häggström, Jens and Lindblad-Toh, Kerstin}},
issn = {{1553-7390}},
language = {{eng}},
number = {{9}},
pages = {{1--34}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Genetics}},
title = {{The genetic consequences of dog breed formation - Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels}},
url = {{http://dx.doi.org/10.1371/journal.pgen.1009726}},
doi = {{10.1371/journal.pgen.1009726}},
volume = {{17}},
year = {{2021}},
}