Genome-wide association study for endocrine fertility traits using single nucleotide polymorphism arrays and sequence variants in dairy cattle.

Endocrine fertility traits, which are defined from progesterone concentration levels in milk, are interesting indicators of dairy cow fertility because they more directly reflect the cows own reproductive physiology than classical fertility traits, which are more biased by farm management decisions. The aim of this study was to detect quantitative trait loci (QTL) for 7 endocrine fertility traits in dairy cows by performing a genome-wide association study with 85k single nucleotide polymorphisms (SNP), and then fine-map targeted QTL regions, using imputed sequence variants. Two classical fertility traits were also analyzed for QTL with 85k SNP. The association between a SNP and a phenotype was assessed by single-locus regression for each SNP, using a linear mixed model that included a random polygenic effect. A total of 2,447 Holstein Friesian cows with 5,339 lactations with both phenotypes and genotypes were used for association analysis. Heritability estimates ranged from 0.09 to 0.15 for endocrine fertility traits and 0.03 to 0.10 for classical fertility traits. The genome-wide association study identified 17 QTL regions for endocrine fertility traits on Bos taurus autosomes (BTA) 2, 3, 8, 12, 15, 17, 23, and 25. The highest number (5) of QTL regions from the genome-wide association study was identified for the endocrine trait "proportion of samples with luteal activity." Overlapping QTL regions were found between endocrine traits on BTA 2, 3, and 17. For the classical trait calving to first service, 3 QTL regions were identified on BTA 3, 15, and 23, and an overlapping region was identified on BTA 23 with endocrine traits. Fine-mapping target regions for the endocrine traits on BTA 2 and 3 using imputed sequence variants confirmed the QTL from the genome-wide association study, and identified several associated variants that can contribute to an index of markers for genetic improvement of fertility. Several potential candidate genes underlying endocrine fertility traits were also identified in the target regions and are discussed. However, due to high linkage disequilibrium, it was not possible to specify genes or polymorphisms as causal factors for any of the regions.

Tenghe AMM ，Bouwman AC ，Berglund B ，Strandberg E ，de Koning DJ ，Veerkamp RF ... -  《-》

Genome-wide association study of normal and atypical progesterone profiles in Holstein-Friesian dairy cows.

Female fertility has a major role in dairy production and affects the profitability of dairy cattle. The genetic progress obtained by traditional selection can be slow because of the low heritability of classical fertility traits. Endocrine fertility traits based on progesterone concentration in milk have higher heritability and more directly reflect the cow's own reproductive physiology. The aim of our study was to identify genomic regions for 7 endocrine fertility traits in dairy cows by performing a genome-wide association study with 54,000 SNP. The next step was to fine-map targeted genomic regions with significant SNP using imputed sequences to identify potential candidate genes associated with the normal and atypical progesterone profiles. The association between a SNP and a phenotype was assessed by a single SNP analysis, using a linear mixed model that included a random polygenic effect. Phenotypes and genotypes were available for 1,126 primiparous and multiparous Holstein-Friesian cows from research herds in Ireland, the Netherlands, Sweden, and the United Kingdom. In total, 44 significant SNP associated with 7 endocrine fertility traits were identified on Bos taurus autosome (BTA) 1-4, 6, 8-9, 11-12, 14-17, 19, 21-24, and 29. Three chromosomes, BTA8, BTA17, and BTA23, were imputed from 54,000 SNP genotypes to the whole-genome sequence level with Beagle version 4.1. The fine-mapping identified several significant associations with delayed cyclicity, cessation of cyclicity, commencement of luteal activity, and inter-ovulatory interval. These associations may contribute to an index of markers for genetic improvement of fertility. Several potential candidate genes reported to affect reproduction were also identified in the targeted genomic regions. However, due to high linkage disequilibrium, it was not possible to identify putative causal genes or polymorphisms for any of the regions.

Nyman S ，Duchemin SI ，de Koning DJ ，Berglund B ... -  《-》

Genome-wide associations for fertility traits in Holstein-Friesian dairy cows using data from experimental research herds in four European countries.

Genome-wide association studies for difficult-to-measure traits are generally limited by the sample population size with accurate phenotypic data. The objective of this study was to utilise data on primiparous Holstein-Friesian cows from experimental farms in Ireland, the United Kingdom, the Netherlands and Sweden to identify genomic regions associated with traditional measures of fertility, as well as a fertility phenotype derived from milk progesterone profiles. Traditional fertility measures investigated were days to first heat, days to first service, pregnancy rate to first service, number of services and calving interval (CI); post-partum interval to the commencement of luteal activity (CLA) was derived using routine milk progesterone assays. Phenotypic and genotypic data on 37 590 single nucleotide polymorphisms (SNPs) were available for up to 1570 primiparous cows. Genetic parameters were estimated using linear animal models, and univariate and bivariate genome-wide association analyses were undertaken using Bayesian stochastic search variable selection performed using Gibbs sampling. Heritability estimates of the traditional fertility traits varied from 0.03 to 0.16; the heritability for CLA was 0.13. The posterior quantitative trait locus (QTL) probabilities, across the genome, for the traditional fertility measures were all <0.021. Posterior QTL probabilities of 0.060 and 0.045 were observed for CLA on SNPs each on chromosome 2 and chromosome 21, respectively, in the univariate analyses; these probabilities increased when CLA was included in the bivariate analyses with the traditional fertility traits. For example, in the bivariate analysis with CI, the posterior QTL probability of the two aforementioned SNPs were 0.662 and 0.123. Candidate genes in the vicinity of these SNPs are discussed. The results from this study suggest that the power of genome-wide association studies in cattle may be increased by sharing of data and also possibly by using physiological measures of the trait under investigation.

Berry DP ，Bastiaansen JW ，Veerkamp RF ，Wijga S ，Wall E ，Berglund B ，Calus MP ... -  《-》

Genome-wide association mapping for female fertility traits in Danish and Swedish Holstein cattle.

A genome-wide association study was conducted using a mixed model analysis for QTL for fertility traits in Danish and Swedish Holstein cattle. The analysis incorporated 2,531 progeny tested bulls, and a total of 36,387 SNP markers on 29 bovine autosomes were used. Eleven fertility traits were analyzed for SNP association. Furthermore, mixed model analysis was used for association analyses where a polygenic effect was fitted as a random effect, and genotypes at single SNPs were successively included as a fixed effect in the model. The Bonferroni correction for multiple testing was applied to adjust the significance threshold. Seventy-four SNP-trait combinations showed chromosome-wide significance, and five of these were significant genome-wide. Twenty-four QTL regions on 14 chromosomes were detected. Strong evidence for the presence of QTL that affect fertility traits were observed on chromosomes 3, 5, 10, 13, 19, 20, and 24. The QTL intervals were generally smaller than those described in earlier linkage studies. The identification of fertility trait-associated SNPs and mapping of the corresponding QTL in small chromosomal regions reported here will facilitate searches for candidate genes and candidate polymorphisms.

Sahana G ，Guldbrandtsen B ，Bendixen C ，Lund MS ... -  《-》

Genome-wide association study of endo-parasite phenotypes using imputed whole-genome sequence data in dairy and beef cattle.

Quantitative genetic studies suggest the existence of variation at the genome level that affects the ability of cattle to resist to parasitic diseases. The objective of the current study was to identify regions of the bovine genome that are associated with resistance to endo-parasites. Individual cattle records were available for Fasciola hepatica-damaged liver from 18 abattoirs. Deregressed estimated breeding values (EBV) for F. hepatica-damaged liver were generated for genotyped animals with a record for F. hepatica-damaged liver and for genotyped sires with a least one progeny record for F. hepatica-damaged liver; 3702 animals were available. In addition, individual cow records for antibody response to F. hepatica on 6388 genotyped dairy cows, antibody response to Ostertagia ostertagi on 8334 genotyped dairy cows and antibody response to Neospora caninum on 4597 genotyped dairy cows were adjusted for non-genetic effects. Genotypes were imputed to whole-sequence; after edits, 14,190,141 single nucleotide polymorphisms (SNPs) and 16,603,644 SNPs were available for cattle with deregressed EBV for F. hepatica-damaged liver and cows with an antibody response to a parasitic disease, respectively. Association analyses were undertaken using linear regression on one SNP at a time, in which a genomic relationship matrix accounted for the relationships between animals. Genomic regions for F. hepatica-damaged liver were located on Bos taurus autosomes (BTA) 1, 8, 11, 16, 17 and 18; each region included at least one SNP with a p value lower than 10. Five SNPs were identified as significant (q value < 0.05) for antibody response to N. caninum and were located on BTA21 or 25. For antibody response to F. hepatica and O. ostertagi, six and nine quantitative trait loci (QTL) regions that included at least one SNP with a p value lower than 10 were identified, respectively. Gene set enrichment analysis revealed a significant association between functional annotations related to the olfactory system and QTL that were suggestively associated with endo-parasite phenotypes. A number of novel genomic regions were suggestively associated with endo-parasite phenotypes across the bovine genome and two genomic regions on BTA21 and 25 were associated with antibody response to N. caninum.

Twomey AJ ，Berry DP ，Evans RD ，Doherty ML ，Graham DA ，Purfield DC ... -  《-》