Single-step genome-wide association analyses for milk urea concentration in Walloon Holstein cows.

The aims of this study were to conduct a single-step genome-wide association to identify genomic regions associated with milk urea (MU) and to estimate genetic correlations between MU and milk yield (MY), milk composition (calcium content [CC], fat percentage [FP], protein percentage [PP], and casein percentage [CNP]), and cheese-making properties (CMP; coagulation time [CT], curd firmness after 30 min from rennet addition [a30], and titratable acidity [TA]). The used data have been collected from 2015 to 2020 on 78,073 first-parity (485,218 test-day records) and 48,766 second-parity (284,942 test-day records) Holstein cows distributed in 671 herds in the Walloon Region of Belgium. Data of 565,533 SNP located on 29 BTA of 6,617 animals (1,712 males) were used. Random regression test-day models were used to estimate genetic parameters through the Bayesian Gibbs sampling method. The SNP solutions were estimated using a single-step genomic BLUP approach. The proportion of the total additive genetic variance explained by windows of 50 consecutive SNPs (with an average size of ∼216 kb) was calculated, and the top-3 genomic regions explaining the largest rate of the genetic variance were considered promising regions and used to identify potential candidate genes. Mean (SD) MU was 25.38 (8.02) mg/dL and 25.03 (8.06) mg/dL in the first and second lactation, respectively. Mean heritability estimates for daily MU were 0.21 and 0.23 for the first and second lactation, respectively. The genetic correlations estimated between MU and MY, milk composition, and CMP were quite low (ranged from -0.10 [CC] to 0.10 [TA] and -0.05 [CT] to 0.13 [TA] for the first and second lactations, respectively). The top-3 regions associated with MU were located from 80.61 to 80.74 Mb on BTA6, 103.26 to 103.41 Mb on BTA11, and 1.59 to 2.15 Mb on BTA14. Genes including KCNT1, MROH1, SHARPIN, TSSK5, CPSF1, HSF1, TONSL, DGAT1, SCX, and MAF1 were identified as positional candidate genes for MU. The findings of this study can be used for a better understanding of the genomic architecture underlying MU in Holstein cattle.

Single-step genome-wide association analyses for selected infrared-predicted cheese-making traits in Walloon Holstein cows.

This study aimed to perform genome-wide association study to identify genomic regions associated with milk production and cheese-making properties (CMP) in Walloon Holstein cows. The studied traits were milk yield, fat percentage, protein percentage, casein percentage (CNP), calcium content, somatic cell score (SCS), coagulation time, curd firmness after 30 min from rennet addition, and titratable acidity. The used data have been collected from 2014 to 2020 on 78,073 first-parity (485,218 test-day records), 48,766 second-parity (284,942 test-day records), and 21,948 third-parity (105,112 test-day records) Holstein cows distributed in 671 herds in the Walloon Region of Belgium. Data of 565,533 single nucleotide polymorphisms (SNP), located on 29 Bos taurus autosomes (BTA) of 6,617 animals (1,712 males), were used. Random regression test-day models were used to estimate genetic parameters through the Bayesian Gibbs sampling method. The SNP solutions were estimated using a single-step genomic BLUP approach. The proportion of the total additive genetic variance explained by windows of 50 consecutive SNPs (with an average size of ∼216 KB) was calculated, and regions accounting for at least 1.0% of the total additive genetic variance were used to search for positional candidate genes. Heritability estimates for the studied traits ranged from 0.10 (SCS) to 0.53 (CNP), 0.10 (SCS) to 0.50 (CNP), and 0.12 (SCS) to 0.49 (CNP) in the first, second, and third parity, respectively. Genome-wide association analyses identified 6 genomic regions (BTA1, BTA14 [4 regions], and BTA20) associated with the considered traits. Genes including the SLC37A1 (BTA1), SHARPIN, MROH1, DGAT1, FAM83H, TIGD5, MROH6, NAPRT, ADGRB1, GML, LYPD2, JRK (BTA14), and TRIO (BTA20) were identified as positional candidate genes for the studied CMP. The findings of this study help to unravel the genomic background of a cow's ability for cheese production and can be used for the future implementation and use of genomic evaluation to improve the cheese-making traits in Walloon Holstein cows.

Single-step genome-wide association for selected milk fatty acids in Dual-Purpose Belgian Blue cows.

The aim of this study was to estimate genetic parameters and identify genomic regions associated with selected individual and groups of milk fatty acids (FA) predicted by milk mid-infrared spectrometry in Dual-Purpose Belgian Blue cows. The used data were 69,349 test-day records of milk yield, fat percentage, and protein percentage along with selected individual and groups FA of milk (g/dL milk) collected from 2007 to 2020 on 7,392 first-parity (40,903 test-day records), and 5,185 second-parity (28,446 test-day records) cows distributed in 104 herds in the Walloon Region of Belgium. Data of 28,466 SNPs, located on 29 Bos taurus autosomes (BTA), of 1,699 animals (639 males and 1,060 females) were used. Random regression test-day models were used to estimate genetic parameters through the Bayesian Gibbs sampling method. The SNP solutions were estimated using a single-step genomic best linear unbiased prediction approach. The proportion of genetic variance explained by each 25-SNP sliding window (with an average size of ~2 Mb) was calculated, and regions accounting for at least 1.0% of the total additive genetic variance were used to search for candidate genes. Average daily heritability estimated for the included milk FA traits ranged from 0.01 (C4:0) to 0.48 (C12:0) and 0.01 (C4:0) to 0.42 (C12:0) in the first and second parities, respectively. Genetic correlations found between milk yield and the studied individual milk FA, except for C18:0, C18:1 trans, C18:1 cis-9, were positive. The results showed that fat percentage and protein percentage were positively genetically correlated with all studied individual milk FA. Genome-wide association analyses identified 11 genomic regions distributed over 8 chromosomes [BTA1, BTA4, BTA10, BTA14 (4 regions), BTA19, BTA22, BTA24, and BTA26] associated with the studied FA traits, though those found on BTA14 partly overlapped. The genomic regions identified differed between parities and lactation stages. Although these differences in genomic regions detected may be due to the power of quantitative trait locus detection, it also suggests that candidate genes underlie the phenotypic expression of the studied traits may vary between parities and lactation stages. These findings increase our understanding about the genetic background of milk FA and can be used for the future implementation of genomic evaluation to improve milk FA profile in Dual-Purpose Belgian Blue cows.

Detailed analysis of mortality rates in the female progeny of 1,001 Holstein bulls allows the discovery of new dominant genetic defects.

Reducing juvenile mortality in cattle is important for both economic and animal welfare reasons. Previous studies have revealed a large variability in mortality rates between breeds and sire progeny groups, with some extreme cases due to dominant mutations causing various syndromes among the descendants of mosaic bulls. The purpose of this study was to monitor sire-family calf mortality within the French and Walloon Holstein populations, and to use this information to detect genetic defects that might have been overlooked by lack of specific symptoms. In a population of heifers born from 1,001 bulls between 2017 and 2020, the average sire-family mortality rates were of 11.8% from birth to 1 year of age and of 4.2, 2.9, 3.1, and 3.2% for the perinatal, postnatal, preweaning, and postweaning subperiods, respectively. After outlining the 5 worst bulls per category, we paid particular attention to the bulls Mo and Pa, because they were half-brothers. Using a battery of approaches, including necropsies, karyotyping, genetic mapping, and whole-genome sequencing, we described 2 new independent genetic defects in their progeny and their molecular etiology. Mo was found to carry a de novo reciprocal translocation between chromosomes BTA26 and BTA29, leading to increased embryonic and juvenile mortality because of aneuploidy. Clinical examination of 2 calves that were monosomic for a large proportion of BTA29, including an orthologous segment deleted in human Jacobsen syndrome, revealed symptoms shared between species. In contrast, Pa was found to be mosaic for a dominant de novo nonsense mutation of GATA 6 binding protein (GATA6), causing severe cardiac malformations. In conclusion, our results highlight the power of monitoring juvenile mortality to identify dominant genetic defects due to de novo mutation events.

Genome-wide association study for selected cheese-making properties in Dual-Purpose Belgian Blue cows.

This study aimed to estimate genetic parameters and identify genomic region(s) associated with selected cheese-making properties (CMP) in Dual-Purpose Belgian Blue (DPBB) cows. Edited data were 46,301 test-day records of milk yield, fat percentage, protein percentage, casein percentage, milk calcium content (CC), coagulation time (CT), curd firmness after 30 min from rennet addition (a30), and milk titratable acidity (MTA) collected from 2014 to 2020 on 4,077 first-parity (26,027 test-day records), and 3,258 second-parity DPBB cows (20,274 test-day records) distributed in 124 herds in the Walloon Region of Belgium. Data of 28,266 SNP, located on 29 Bos taurus autosomes (BTA) of 1,699 animals were used. Random regression test-day models were used to estimate genetic parameters through the Bayesian Gibbs sampling method. The SNP solutions were estimated using a single-step genomic BLUP approach. The proportion of the total additive genetic variance explained by windows of 25 consecutive SNPs (with an average size of ∼2 Mb) was calculated, and regions accounting for at least 1.0% of the total additive genetic variance were used to search for candidate genes. Heritability estimates for the included CMP ranged from 0.19 (CC) to 0.50 (MTA), and 0.24 (CC) to 0.41 (MTA) in the first and second parity, respectively. The genetic correlation estimated between CT and a30 varied from -0.61 to -0.41 and from -0.55 to -0.38 in the first and second lactations, respectively. Negative genetic correlations were found between CT and milk yield and composition, while those estimated between curd firmness and milk composition were positive. Genome-wide association analyses results identified 4 genomic regions (BTA1, BTA3, BTA7, and BTA11) associated with the considered CMP. The identified genomic regions showed contrasting results between parities and among the different stages of each parity. It suggests that different sets of candidate genes underlie the phenotypic expression of the considered CMP between parities and lactation stages of each parity. The findings of this study can be used for future implementation and use of genomic evaluation to improve the cheese-making traits in DPBB cows.

Myostatin mutation causing double muscling could affect increased psoroptic mange sensitivity in dual purpose Belgian Blue cattle.

Belgian Blue cattle are known for their high degree of muscling and good carcass qualities. This high degree of muscling is mainly caused by a mutation in the myostatin gene (MSTN). Although the MSTN mutation is considered as fixed in the Belgian Blue breed, segregation is occurring in a sub-population bred for dual purpose. In the latter population, we observed an association between the mutation in MSTN and susceptibility to psoroptic mange, a skin disease caused by Psoroptes ovis mites that heavily plagues Belgian Blue cattle. In total, 291 animals were sampled and screened for their susceptibility for mange lesions and their MSTN genotype. Via linear mixed modelling, we observed that homozygous mutant animals had a significant increase in the size of mange lesions (+2.51% lesion extent) compared to homozygous wild type. These findings were confirmed with zero-inflated modelling, an animal model and odds analysis. Risk ratios for developing severe mange lesions were 5.9 times as high for homozygous mutant animals. All analyses confirmed an association between the MSTN genotype and psoroptic mange lesion size.

Bayesian single-step genomic evaluations combining local and foreign information in Walloon Holsteins.

Most dairy cattle populations found in different countries around the world are small to medium sized and use many artificial insemination bulls imported from different foreign countries. The Walloon population in the southern part of Belgium is a good example for such a small-scale population. Wallonia has also a very active community of Holstein breeders requesting high level genetic evaluation services. Single-step Genomic BLUP (ssGBLUP) methods allow the simultaneous use of genomic, pedigree and phenotypic information and could reduce potential biases in the estimation of genomically enhanced breeding values (GEBV). Therefore, in the context of implementing a Walloon genomic evaluation system for Holsteins, it was considered as the best option. However, in contrast to multi-step genomic predictions, natively ssGBLUP will only use local phenotypic information and is unable to use directly important other sources of information coming from abroad, for example Multiple Across Country Evaluation (MACE) results as provided by the Interbull Center (Uppsala, Sweden). Therefore, we developed and implemented single-step Genomic Bayesian Prediction (ssGBayes), as an alternative method for the Walloon genomic evaluations. The ssGBayes method approximated the correct system of equations directly using estimated breeding values (EBV) and associated reliabilities (REL) without any explicit deregression step. In the Walloon genomic evaluation, local information refers to Walloon EBV and REL and foreign information refers to MACE EBV and associated REL. Combining simultaneously all available genotypes, pedigree, local and foreign information in an evaluation can be achieved but adding contributions to left-hand and right-hand sides subtracting double-counted contributions. Correct propagation of external information avoiding double counting of contributions due to relationships and due to records can be achieved. This ssGBayes method computed more accurate predictions for all types of animals. For example, for genotyped animals with low Walloon REL (<0.25) without MACE results but sired by genotyped bulls with MACE results, the average increase of REL for the studied traits was 0.38 points of which 0.08 points could be traced to the inclusion of MACE information. For other categories of genotyped animals, the contribution by MACE information was also high. The Walloon genomic evaluation system passed for the first time the Interbull GEBV tests for several traits in July 2013. Recent experiences reported here refer to its use in April 2016 for the routine genomic evaluations of milk production, udder health and type traits. Results showed that the proposed methodology should also be of interest for other, similar, populations.