Genome-Wide Association Analyses of Fertility Traits in Beef Heifers

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2021 Feb 5

PMID 33540904

Citations 9

Authors

Morgan R Stegemiller

Gordon K Murdoch

Troy N Rowan

Kimberly M Davenport

Gabrielle M Becker

John B Hall

Brenda M Murdoch

Affiliations

Soon will be listed here.

Abstract

The ability of livestock to reproduce efficiently is critical to the sustainability of animal agriculture. Antral follicle count (AFC) and reproductive tract scores (RTS) can be used to estimate fertility in beef heifers, but the genetic mechanisms influencing variation in these measures are not well understood. Two genome-wide association studies (GWAS) were conducted to identify the significant loci associated with these traits. In total, 293 crossbred beef heifers were genotyped on the Bovine GGP 50K chip and genotypes were imputed to 836,121 markers. A GWAS was performed with the AFC phenotype for 217 heifers with a multi-locus mixed model, conducted using the year, age at time of sampling and principal component analysis groupings as the covariates. The RTS GWAS was performed with 289 heifers using an additive correlation/trend test comparing prepubertal to pubertal heifers. The loci on chromosomes 2, 3 and 23 were significant in the AFC GWAS and the loci on chromosomes 2, 8, 10 and 11 were significant in the RTS GWAS. The significant region on chromosome 2 was similar between both analyses. These regions contained genes associated with cell proliferation, transcription, apoptosis and development. This study proposes candidate genes for beef cattle fertility, although future research is needed to elucidate the precise mechanisms.

Citing Articles

Genome-Wide Association Integrating a Transcriptomic Meta-Analysis Suggests That Genes Related to Fat Deposition and Muscle Development Are Closely Associated with Growth in Huaxi Cattle.

Liu C, Ren T, Ruan P, Huang Y, Ceccobelli S, Huang D Vet Sci. 2025; 12(2).

PMID: 40005876 PMC: 11860805. DOI: 10.3390/vetsci12020109.

Beef Cattle Genome Project: Advances in Genome Sequencing, Assembly, and Functional Genes Discovery.

Gao Z, Lu Y, Chong Y, Li M, Hong J, Wu J Int J Mol Sci. 2024; 25(13).

PMID: 39000250 PMC: 11240973. DOI: 10.3390/ijms25137147.

Puberty classifications in beef heifers are moderately to highly heritable and associated with candidate genes related to cyclicity and timing of puberty.

Hess M, Mersha A, Ference S, Nafziger S, Keane J, Fuller A Front Genet. 2024; 15:1405456.

PMID: 38939530 PMC: 11208629. DOI: 10.3389/fgene.2024.1405456.

Genome-wide association study identifies genomic regions associated with key reproductive traits in Korean Hanwoo cows.

Haque M, Lee Y, Ha J, Jin S, Park B, Kim N BMC Genomics. 2024; 25(1):496.

PMID: 38778305 PMC: 11112828. DOI: 10.1186/s12864-024-10401-3.

Mapping Expression Quantitative Trait Loci Targeting Candidate Genes for Pregnancy in Beef Cows.

Diniz W, Afonso J, Kertz N, Dyce P, Banerjee P Biomolecules. 2024; 14(2).

PMID: 38397387 PMC: 10886872. DOI: 10.3390/biom14020150.

References

Neupane M, Geary T, Kiser J, Burns G, Hansen P, Spencer T . Loci and pathways associated with uterine capacity for pregnancy and fertility in beef cattle. PLoS One. 2017; 12(12):e0188997. PMC: 5724891. DOI: 10.1371/journal.pone.0188997. View

MURANO S, Thweatt R, Shmookler Reis R, Jones R, Moerman E, Goldstein S . Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence. Mol Cell Biol. 1991; 11(8):3905-14. PMC: 361182. DOI: 10.1128/mcb.11.8.3905-3914.1991. View

Das S, Forer L, Schonherr S, Sidore C, Locke A, Kwong A . Next-generation genotype imputation service and methods. Nat Genet. 2016; 48(10):1284-1287. PMC: 5157836. DOI: 10.1038/ng.3656. View

Xu Y, Johansson M, Karlsson A . Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria. J Biol Chem. 2007; 283(3):1563-1571. DOI: 10.1074/jbc.M707997200. View

Segura V, Vilhjalmsson B, Platt A, Korte A, Seren U, Long Q . An efficient multi-locus mixed-model approach for genome-wide association studies in structured populations. Nat Genet. 2012; 44(7):825-30. PMC: 3386481. DOI: 10.1038/ng.2314. View

Jimenez-Krassel F, Scheetz D, Neuder L, Pursley J, Ireland J . A single ultrasound determination of ≥25 follicles ≥3 mm in diameter in dairy heifers is predictive of a reduced productive herd life. J Dairy Sci. 2017; 100(6):5019-5027. DOI: 10.3168/jds.2016-12277. View

Shkolnik K, Tadmor A, Ben-Dor S, Nevo N, Galiani D, Dekel N . Reactive oxygen species are indispensable in ovulation. Proc Natl Acad Sci U S A. 2011; 108(4):1462-7. PMC: 3029775. DOI: 10.1073/pnas.1017213108. View

Fortes M, Reverter A, Nagaraj S, Zhang Y, Jonsson N, Barris W . A single nucleotide polymorphism-derived regulatory gene network underlying puberty in 2 tropical breeds of beef cattle. J Anim Sci. 2011; 89(6):1669-83. DOI: 10.2527/jas.2010-3681. View

Fan H, Liu Z, Shimada M, Sterneck E, Johnson P, Hedrick S . MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science. 2009; 324(5929):938-41. PMC: 2847890. DOI: 10.1126/science.1171396. View

10.

Gandhi V, Samuels D . Enzyme kinetics of the mitochondrial deoxyribonucleoside salvage pathway are not sufficient to support rapid mtDNA replication. PLoS Comput Biol. 2011; 7(8):e1002078. PMC: 3150320. DOI: 10.1371/journal.pcbi.1002078. View

11.

Jimenez-Krassel F, Folger J, Ireland J, Smith G, Hou X, Davis J . Evidence that high variation in ovarian reserves of healthy young adults has a negative impact on the corpus luteum and endometrium during estrous cycles in cattle. Biol Reprod. 2009; 80(6):1272-81. DOI: 10.1095/biolreprod.108.075093. View

12.

Jensen L, Whitehead A . Pellino2 activates the mitogen activated protein kinase pathway. FEBS Lett. 2003; 545(2-3):199-202. DOI: 10.1016/s0014-5793(03)00533-7. View

13.

Martin L, Brinks J, Bourdon R, Cundiff L . Genetic effects on beef heifer puberty and subsequent reproduction. J Anim Sci. 1992; 70(12):4006-17. DOI: 10.2527/1992.70124006x. View

14.

Fang G, Liu J, Wang Q, Huang X, Yang R, Pang Y . MicroRNA-223-3p Regulates Ovarian Cancer Cell Proliferation and Invasion by Targeting SOX11 Expression. Int J Mol Sci. 2017; 18(6). PMC: 5486031. DOI: 10.3390/ijms18061208. View

15.

Salilew-Wondim D, Wang Q, Tesfaye D, Schellander K, Hoelker M, Hossain M . Polycystic ovarian syndrome is accompanied by repression of gene signatures associated with biosynthesis and metabolism of steroids, cholesterol and lipids. J Ovarian Res. 2015; 8:24. PMC: 4414284. DOI: 10.1186/s13048-015-0151-5. View

16.

Reynolds M, Chibisa G, Ahmadzadeh A, Hall J . Reproductive development and fertility traits among heifers in different residual feed intake groups. Transl Anim Sci. 2020; 2(Suppl 1):S175-S179. PMC: 7200874. DOI: 10.1093/tas/txy039. View

17.

Abedini A, Zamberlam G, Lapointe E, Tourigny C, Boyer A, Paquet M . WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. FASEB J. 2015; 30(4):1534-47. PMC: 4799500. DOI: 10.1096/fj.15-280313. View

18.

Silva-Santos K, Siloto L, Santos G, Morotti F, Marcantonio T, Seneda M . Comparison of antral and preantral ovarian follicle populations between Bos indicus and Bos indicus-taurus cows with high or low antral follicles counts. Reprod Domest Anim. 2013; 49(1):48-51. DOI: 10.1111/rda.12222. View

19.

Diaczok D, Divall S, Matsuo I, Wondisford F, Wolfe A, Radovick S . Deletion of Otx2 in GnRH neurons results in a mouse model of hypogonadotropic hypogonadism. Mol Endocrinol. 2011; 25(5):833-46. PMC: 3082331. DOI: 10.1210/me.2010-0271. View

20.

Shynlova O, Bortolini M, Alarab M . Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause. Int Braz J Urol. 2013; 39(2):257-67. DOI: 10.1590/S1677-5538.IBJU.2013.02.15. View