TY - JOUR

T1 - Genome-wide association study with imputed whole-genome sequence variants including large deletions for female fertility in 3 Nordic dairy cattle breeds

AU - Mesbah-Uddin, Md

AU - Guldbrandtsen, Bernt

AU - Capitan, Aurélien

AU - Lund, Mogens Sandø

AU - Boichard, Didier

AU - Sahana, Goutam

N1 - Publisher Copyright: © 2022 American Dairy Science Association

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - dairy cattle

KW - deletion

KW - fertility

KW - genome-wide association study

U2 - 10.3168/jds.2021-20655

DO - 10.3168/jds.2021-20655

M3 - Journal article

C2 - 34955274

AN - SCOPUS:85121683735

VL - 105

SP - 1298

EP - 1313

JO - Journal of Dairy Science

JF - Journal of Dairy Science

SN - 0022-0302

IS - 2

ER -