Genome-Wide Association Analyses of Fertility Traits in Beef Heifers

Stegemiller, Morgan R.; Murdoch, Gordon K.; Rowan, Troy N.; Davenport, Kimberly M; Becker, Gabrielle M.; Hall, J. B.; Murdoch, Brenda M.

doi:10.3390/genes12020217

Cited by 16 publications

(25 citation statements)

References 62 publications

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“…This SNP lies within NLGN4X, a neuronal cell surface protein with links to autism and Asperger syndrome. None of the regions identified in the current study overlap with other AFC GWAS results, although only literature reports for beef (Stegemiller et al, 2021) or Nellore cattle could be found (Oliveira Júnior et al, 2019;Grigoletto et al, 2020). The potential of a genomic marker for AFC is useful, as measuring AFC is time consuming and difficult in a nonresearch capacity.…”

Section: Discussionmentioning

confidence: 48%

“…Determination of pathways involved may highlight key networks of genes influencing fertility and prenatal reproductive development. Genetic variation has been identified that is associated with AFC in beef heifers on chromosomes 2, 3, and 23 (Stegemiller et al, 2021). In Nellore cattle, regions of interest included chromosomes 1 and 26, which accounted for 6.2 and 7.3% of the total additive genetic variance, respectively (Grigoletto et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Investigating anogenital distance and antral follicle count as novel markers of fertility within a herd of cows with positive or negative genetic merit for fertility traits

Grala

Price

Kuhn-Sherlock

et al. 2021

Journal of Dairy Science

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Using early-in-life markers of reproductive characteristics may enhance the speed and success of genetic improvement in fertility. We investigated 2 phenotypes that can be measured early in life and are moderately heritable to determine their association with traditional measures of reproductive success and genetic variation under a seasonal-calving, pasture-based system. Cows were bred to be divergent in the New Zealand Fertility Breeding Value, which estimates genetic merit for fertility. Cows consisted of 2 groups with an average positive (+5%) or negative (−5%) genetic merit for fertility traits and were expected to have large diversity in reproductive outcomes. Calves were genotyped at 41 ± 3.1 d of age (mean ± SD; n = 538), and antral follicle counts (AFC) were measured when they were postpubertal heifers before their first breeding (416 ± 15 d old; 92-d range; n = 520). The anogenital distance (AGD) was measured in 478 primiparous cows of this same population 50 to 60 d after the breeding start date when they were 881 ± 25 d old (145-d range). The AGD was shorter in animals with a positive genetic merit for fertility traits (based on parent averages). An indicator of herd reproductive success in a seasonalcalving system (recalving by 6 wk in lactation 2) was chosen for logistic regression with cross-validation, and if significant, a cut-off was calculated that categorized animals into groups. Both linear and quadratic regression was undertaken, and the model with the greatest sensitivity for detection of nonpregnant cows used. The AGD linear model was significant with a sensitivity of 64% and a specificity of 48%. This model resulted in a cut-off of 102 mm, which we used to classify cows as short (≤102 mm) or long (>102 mm) AGD animals. Primiparous cows with a short AGD were more likely to be pregnant within the first 3 and 6 wk of mating, and become pregnant as a primiparous cow, than those with a long AGD. The time from calving to conception was 20 d earlier in short AGD compared with long-AGD cows. None of the models tested for AFC were significant; therefore cows were categorized into 3 groups based on previous work in seasonal systems. However, associations between fertility phenotypes and AFC group were limited. Genomic regions of interest for AGD and AFC did not overlap, indicating phenotypes were genetically independent. Overall, AGD appears as a promising early marker of fertility in seasonal grazing systems.

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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Investigating anogenital distance and antral follicle count as novel markers of fertility within a herd of cows with positive or negative genetic merit for fertility traits

Grala

Price

Kuhn-Sherlock

et al. 2021

Journal of Dairy Science

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“…After filtering, 575,053 genotypes from 22 animals were used for association analysis conducted in PLINK [45] using Fisher’s exact test. Locus association was inferred at alpha = 1×10 -5 , as reported by The Wellcome Trust Case Control Consortium [56] for case-control studies and previous GWAS analyses of reproductive traits in cows or heifers [4, 25, 32].…”

Section: Methodsmentioning

confidence: 99%

“…Another potential avenue for the identification of infertile heifers is the use of molecular phenotyping [24]. The pioneering efforts focused on genome-wide association studies (GWAS) to identify genetic markers associated with heifer fertility [4,12,[25][26][27][28][29][30][31][32][33][34][35][36][37][38], but only a few seem to be reproducible across populations [37]. More recent efforts have also focused on transcriptome [39][40][41] and metabolome [42] datasets characterizing these molecules in blood samples.…”

Section: Introductionmentioning

confidence: 99%

A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

Marrella

Biase

2022

Preprint

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Background: Infertility or subfertility is a critical barrier to sustainable cattle production, including in heifers. The development of heifers that do not produce a calf within an optimum window of time is a critical factor for the profitability and sustainability of the cattle industry. The early identification of heifers with optimum fertility using molecular phenotyping is a promising approach to improving sustainability in beef and dairy cattle production. Results: Using a high-density single nucleotide polymorphism (SNP) chip, we collected genotypic data from 575,053 SNPs. We also produced quantitative transcriptome data for 12,445 genes (12,105 protein-coding genes, 228 long non-coding RNAs, and 112 pseudogenes) and proteome data for 213 proteins. We identified two SNPs significantly associated with heifer fertility (rs110918927, chr12: 85648422, P = 6.7x10-7; and rs109366560, chr11:37666527, P = 2.6x10-5). We identified two genes with differential transcript abundance (eFDR ≤ 0.002) between the two groups (Fertile and Sub-Fertile): Adipocyte Plasma Membrane Associated Protein (APMAP, 1.16 greater abundance in the Fertile group) and Dynein Axonemal Intermediate Chain 7 (DNAI7, 1.23 greater abundance in the Sub-Fertile group). Our analysis revealed that the protein Alpha-ketoglutarate-dependent dioxygenase FTO was more abundant in the plasma collected from Fertile heifers relative to their Sub-Fertile counterparts (FDR < 0.05). Interestingly, two proteins did not reach the significance threshold in the model accounting for all samples (Apolipoprotein C-II, APOC2 (FDRglmm = 0.06) and Lymphocyte cytosolic protein 1, LCP1 (FDRglmm = 0.06)), but both proteins were less abundant in the plasma of Fertile Holstein heifers (P < 0.05). Lastly, an integrative analysis of the three datasets identified a series of features (SNPs, gene transcripts, and proteins) that can be useful for the discrimination of heifers based on their fertility. When all features were utilized together, 21 out of 22 heifers were classified correctly based on their fertility category. Conclusions: Our multi-omics analyses confirm the complex nature of female fertility. Very importantly, our results also highlight differences in the molecular profile of heifers associated with fertility that transcend the constraints of breed-specific genetic background.

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“…Speidel et al found some quantitative traits loci (QTL) that are presumed to be associated with heifer pregnancy and stayability [38]. Some additional fertility traits that have been studied include antral follicular count (AFC) and reproductive tract score (RTS), with a sample size of 293 heifers [39]. Even though all those studies were able to find some loci and candidate genes associated with reproduction, the researchers concluded that validation studies were needed as they were not sure about the results.…”

Section: Previously Studied Reproductive Traits At the Genetic Levelmentioning

confidence: 99%

Genomics of heifer pregnancy, days open, and days to conception in Red Angus heifers

Tuyishimire¹

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Although it is challenging to collect information on reproductive traits, fertility traits are believed to play a significant role in the growth of the beef industry and bring revenue to the producers. It has been challenging to make genetic improvement of fertility traits because of scarce records and their low heritability. The joint analyses of economic and indicator traits provided much information for the analysis of other production traits, resulting in favorable improvement. The same method can be applied to reproductive traits to increase prediction accuracy. Furthermore, the ubiquity of high-throughput genotypes and the development of advanced computational methods give hope that there is a possibility of determining the genetic influence on fertility traits. The advancement in phenotypic collection technology eases the keeping of records on both economic and indicator fertility traits. Also, it allows the development of new traits to be analyzed while reducing the cost of data availability. Heifer Pregnancy (HP) - the ability for a heifer to conceive by the end of the breeding season; Days Open (DO) - days of breeding season a heifer remained open; and Days to Conception (DC) -- the number of days it took for a heifer to get pregnant, are easy to measure fertility traits with enough information to make beef reproductive genetic improvement in the industry. The objective of the current study is to identify DNA markers tagging genes influencing HP, DC, and DC among 18,039 Red Angus heifers, find the genetic relationship among those traits, and creating the genomic predictions of days to conception and days open. The results show a small heritability of 0.119 to 0.131, 0.10 to 0.102, and 0.0749 to 0.112 for HP, DO, and DC, respectively. The DC model resulted in higher accuracy than other models. There was a high correlation between HP and DO (r = - 0.61 and 0.85 from the linear model and the liability scale model, respectively). The de-regressed estimated breeding value (EBV) genomewide association (GWAS) yielded 58 and 2 significant SNPs at suggestive significant level (pvalue [less than] 1.0e-05) for HP and DC, respectively. This study found GRID2 and ZMIZ1 genes to be associated with heifer pregnancy, and it has been speculated that the central nervous system related genes ontology and the hormones it controls might suggest the physiology behind some of the reproductive differences. The present study confirms the low heritability status of fertility traits and shows the possibilities of genetic enhancement based on the obtained accuracies. The identified genes and gene terms will serve as starting points for future studies that might focus on different phenotypes while reducing the cost of phenotyping and improving the accuracy of fertility traits genomic predictions.

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Genome-Wide Association Analyses of Fertility Traits in Beef Heifers

Cited by 16 publications

References 62 publications

Investigating anogenital distance and antral follicle count as novel markers of fertility within a herd of cows with positive or negative genetic merit for fertility traits

Investigating anogenital distance and antral follicle count as novel markers of fertility within a herd of cows with positive or negative genetic merit for fertility traits

A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

Genomics of heifer pregnancy, days open, and days to conception in Red Angus heifers

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