Genome-wide association study with imputed whole-genome sequence variants including large deletions for female fertility in 3 Nordic dairy cattle breeds

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Fertility is an economically important trait in livestock. Poor fertility in dairy cattle can be due to loss-of-function variants affecting any essential gene that causes early embryonic mortality in homozygotes. To identify fertility-associated quantitative trait loci, we performed single-marker association analyses for 8 fertility traits in Holstein, Jersey, and Nordic Red Dairy cattle using imputed whole-genome sequence variants including SNPs, indels, and large deletion. We then performed stepwise selection of independent markers from GWAS loci using conditional and joint association analyses. From single-marker analyses for fertility traits, we reported genome-wide significant associations of 30,384 SNPs, 178 indels, and 3 deletions in Holstein; 23,481 SNPs, 189 indels, and 13 deletions in Nordic Red; and 17 SNPs in Jersey cattle. Conditional and joint association analyses identified 37 and 23 independent associations in Holstein and Nordic Red Dairy cattle, respectively. Fertility-associated GWAS loci were enriched for developmental and cellular processes (Gene Ontology enrichment, false discovery rate < 0.05). For these quantitative trait loci regions (top marker and 500 kb of surrounding regions), we proposed several candidate genes with functional annotations corresponding to embryonic lethality and various fertility-related phenotypes in mouse and cattle. The inclusion of these top markers in future releases of the custom SNP chip used for genomic evaluations will enable their validation in independent populations and improve the accuracy of genomic predictions.

OriginalsprogEngelsk
TidsskriftJournal of Dairy Science
Vol/bind105
Udgave nummer2
Sider (fra-til)1298-1313
Antal sider16
ISSN0022-0302
DOI
StatusUdgivet - 2022
Eksternt udgivetJa

Bibliografisk note

Funding Information:
We are grateful to the Nordic Cattle Genetic Evaluation (NAV), Aarhus, Denmark, for providing the phenotypic data used in this study and Viking Genetics, Randers, Denmark, for providing blood and semen samples for genotyping. This research was supported by the Center for Genomic Selection in Animals and Plants (GenSAP) funded by Innovation Fund Denmark (grant 0603-00519B; Aarhus, Denmark). Md Mesbah-Uddin benefited from a joint grant from the European Commission within the framework of the Erasmus-Mundus joint doctorate “EGS-ABG.” Authors also acknowledge the 1000 Bull Genomes Project and its partners for sharing genomic information. Authors are also grateful to the Genotoul bioinformatics platform Toulouse Midi-Pyrenees (Bioinfo Genotoul) for providing computing and storage resources. This study was part of Md Mesbah-Uddin's PhD thesis formally submitted to GSST, Aarhus University, Denmark, and ABIES, AgroParisTech, France. The authors have not stated any conflicts of interest.

Publisher Copyright:
© 2022 American Dairy Science Association

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