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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

Axelsson, Erik and Ljungvall, Ingrid and Bhoumik, Priyasma and Conn, Laura Bas and Muren, Eva and Ohlsson, Åsa and Olsen, Lisbeth Hoier 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 (2021). 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. PLOS GENETICS. 17
[Research article]

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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 similar to 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.

Authors/Creators:Axelsson, Erik and Ljungvall, Ingrid and Bhoumik, Priyasma and Conn, Laura Bas and Muren, Eva and Ohlsson, Åsa and Olsen, Lisbeth Hoier 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
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
Series Name/Journal:PLOS GENETICS
Year of publishing :2021
Volume:17
Number of Pages:34
Publisher:PUBLIC LIBRARY SCIENCE
ISSN:1553-7404
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 402 Animal and Dairy Science > Animal and Dairy Science.
URN:NBN:urn:nbn:se:slu:epsilon-p-113588
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-113588
Additional ID:
Type of IDID
DOI10.1371/journal.pgen.1009726
Web of Science (WoS)000692132200003
ID Code:25364
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:16 Sep 2021 13:25
Metadata Last Modified:16 Sep 2021 13:31

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