Article (Scientific journals)
Non-additive association analysis using proxy phenotypes identifies novel cattle syndromes.
Reynolds, Edwardo G. M.; Neeley, Catherine; Lopdell, Thomas J. et al.
2021In Nature Genetics, 53 (7), p. 949-954
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Keywords :
Alleles; Animals; Biomarkers; Cattle; Cattle Diseases/diagnosis/epidemiology/etiology; Genome-Wide Association Study; Genotype; Inbreeding; Incidence; Loss of Function Mutation; Phenotype; Syndrome
Abstract :
[en] Mammalian species carry ~100 loss-of-function variants per individual(1,2), where ~1-5 of these impact essential genes and cause embryonic lethality or severe disease when homozygous(3). The functions of the remainder are more difficult to resolve, although the assumption is that these variants impact fitness in less manifest ways. Here we report one of the largest sequence-resolution screens of cattle to date, targeting discovery and validation of non-additive effects in 130,725 animals. We highlight six novel recessive loci with impacts generally exceeding the largest-effect variants identified from additive genome-wide association studies, presenting analogs of human diseases and hitherto-unrecognized disorders. These loci present compelling missense (PLCD4, MTRF1 and DPF2), premature stop (MUS81) and splice-disrupting (GALNT2 and FGD4) mutations, together explaining substantial proportions of inbreeding depression. These results demonstrate that the frequency distribution of deleterious alleles segregating in selected species can afford sufficient power to directly map novel disorders, presenting selection opportunities to minimize the incidence of genetic disease.
Disciplines :
Animal production & animal husbandry
Author, co-author :
Reynolds, Edwardo G. M.
Neeley, Catherine
Lopdell, Thomas J.
Keehan, Michael
Dittmer, Keren
Harland, Chad S.
Couldrey, Christine
Johnson, Thomas J. J.
Tiplady, Kathryn
Worth, Gemma
Walker, Mark
Davis, Stephen R.
Sherlock, Richard G.
Carnie, Katie
Harris, Bevin L.
Charlier, Carole  ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Georges, Michel  ;  Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
Spelman, Richard J.
Garrick, Dorian J.
Littlejohn, Mathew D.
More authors (10 more) Less
Language :
English
Title :
Non-additive association analysis using proxy phenotypes identifies novel cattle syndromes.
Publication date :
2021
Journal title :
Nature Genetics
ISSN :
1061-4036
eISSN :
1546-1718
Publisher :
Nature Publishing Group, United Kingdom
Volume :
53
Issue :
7
Pages :
949-954
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
H2020 - 815668 - BovReg - BovReg - Identification of functionally active genomic features relevant to phenotypic diversity and plasticity in cattle
Funders :
CE - Commission Européenne [BE]
Commentary :
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
Available on ORBi :
since 19 November 2021

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