Opportunities for genomic selection of cheese-making traits in Montbéliarde cows.

As part of the From'MIR project, traits related to the composition and cheese-making properties (CMP) of milk were predicted from 6.6 million mid-infrared spectra taken from 410,622 Montbéliarde cows (19,862 with genotypes). Genome-wide association studies of imputed whole-genome sequences highlighted candidate SNPs that were then added to the EuroG10K BeadChip, which is routinely used in genomic selection. In the present study, we (1) assessed the reliability of single-step genomic BLUP breeding values (ssEBVs) for cheese yields, coagulation traits, and casein and calcium content generated from test-day records of the first 3 lactations, (2) estimated realized genetic trends for these traits over the last decade, and (3) simulated different cheese-making breeding objectives and estimated the responses for CMP as well as for other traits currently selected in the Montbéliarde breed. To estimate the reliability of ssEBVs, the available data were split into 2 independent training and validation sets that respectively contained cows with the oldest and the most recent lactation data. The training set included 155,961 cows (12,850 with genotypes) and was used to predict ssEBVs of 2,125 genotyped cows in the validation set. We first tested 4 models that included either lactation (LACT) or test-day (TD) records from the first (1) or the first 3 (3) lactations, giving equal weight to all 50K SNP effects. Mean reliabilities were 61%, 62%, 63%, and 64% for the LACT1, LACT3, TD1, and TD3 models, respectively. Using the most accurate model (TD3), we then compared the reliabilities of 3 scenarios with: SNPs from the Illumina BovineSNP50 BeadChip only, equally weighted (50K); 50K SNPs plus additional candidate SNPs, equally weighted (50K+); and 50K and candidate SNPs with additional weight given to 7 to 14 candidate SNPs, depending on the trait (CAND). The 50K+ and CAND scenarios led to similar mean reliabilities (67%) and both outperformed the 50K scenario (64%), whereas the CAND scenario generated the less biased ssEBVs. To assess genetic trends, SNP effects were estimated with a single-step GBLUP based on the TD3 model and the 50K scenario applied to the whole population (2.6 million performance records from 190,261 cows and 423,348 animals in the pedigree, of which 21,874 were genotyped) and then applied to 50K genotypes of 21,171 males and 311,761 females. We detected a positive genetic trend for all CMP during the last decade, probably due to selection for an increase in milk protein and fat content in Montbéliarde cows. Finally, we compared the selection responses to 3 different breeding objectives: the current Montbéliarde total merit index (TMI) and 2 alternative scenarios that gave a weight of 70% to TMI and the remaining 30% to either milk casein content (TMI-COMP) or a combination of 3 CMP (TMI-Cheese). The TMI-Cheese scenario yielded the best responses for all the CMP analyzed, whereas values in the TMI-COMP scenario were intermediate, with a slight effect on other traits currently included in TMI. Based on these results, a program of genomic evaluation for CMP predicted from mid-infrared spectra was designed and implemented for the Montbéliarde breed.

Improved dairy cattle mating plans at herd level using genomic information.

From 2012 to 2018, 223 180 Montbéliarde females were genotyped in France and the number of newly genotyped females increased at a rate of about 33% each year. With female genotyping information, farmers have access to the genomic estimated breeding values of the females in their herd and to their carrier status for genetic defects or major genes segregating in the breed. This information, combined with genomic coancestry, can be used when planning matings in order to maximize the expected on-farm profit of future female offspring. We compared different mating allocation approaches for their capacity to maximize the expected genetic gain while limiting expected progeny inbreeding and the probability to conceive an offspring homozygous for a lethal recessive allele. Three mate allocation strategies (random mating (RAND), sequential mating (gSEQ€) and linear programing mating (gLP€)) were compared on 160 actual Montbéliarde herds using male and female genomic information. Then, we assessed the benefit of using female genomic information by comparing matings planned using only female pedigree information with the equivalent strategy using genomic information. We measured the benefit of adding genomic expected inbreeding and risk of conception of an offspring homozygous for a lethal recessive allele to Net merit in mating plans. The influence of three constraints was tested: by relaxing the constraint on availability of a particular semen type (sexed or conventional) for bulls, by adding an upper limit of 8.5% coancestry between mate pairs or by using a more stringent maximum use of a bull in a herd (5% vs 10%). The use of genomic information instead of pedigree information improved the mate allocation method in terms of progeny expected genetic merit, genetic diversity and risk to conceive an offspring homozygous for a lethal recessive allele. Optimizing mate allocation using linear programming and constraining coancestry to a maximum of 8.5% per mate pair reduced the average coancestry with a small impact on expected Net Merit. In summary, for male and female selection pathways, using genomic information is more efficient than using pedigree information to maximize genetic gain while constraining the expected inbreeding of the progeny and the risk to conceive an offspring homozygous for a lethal recessive allele. This study also underlines the key role of semen type (sexed vs conventional) and the associated constraints on the mate allocation algorithm to maximize genetic gain while maintaining genetic diversity and limiting the risk to conceive an offspring homozygous for a lethal recessive allele.

Short communication: Confirmation of candidate causative variants on milk composition and cheesemaking properties in Montbéliarde cows.

In a previous study, we identified candidate causative variants located in 24 functional candidate genes for milk protein and fatty acid composition in Montbéliarde, Normande, and Holstein cows. We designed these variants on the custom part of the EuroG10K BeadChip (Illumina Inc., San Diego, CA), which is routinely used for genomic selection analyses in French dairy cattle. To validate the effects of these candidate variants on milk composition and to estimate their effects on cheesemaking properties, a genome-wide association study was performed on milk protein, fatty acid and mineral composition, as well as on 9 cheesemaking traits (3 laboratory cheese yields, 5 coagulation traits, and milk pH). All the traits were predicted from midinfrared spectra in the Montbéliarde cow population of the Franche-Comté region. A total of 194 candidate variants located in 24 genes and 17 genomic regions were imputed on 19,862 cows with phenotypes and genotyped with either the BovineSNP50 (Illumina Inc.) or the EuroG10K BeadChip. We then tested the effect of each SNP in a mixed linear model including random polygenic effects estimated with a genomic relationship matrix. We confirm here the effects of candidate causative variants located in 17 functional candidate genes on both cheesemaking properties and milk composition traits. In each candidate gene, we identified the most plausible causative variant: 4 are missense in the ALPL, SLC26A4, CSN3, and SCD genes, 7 are located in 5'UTR (AGPAT6), 3' untranslated region (GPT), or upstream (CSN1S1, CSN1S2, PAEP, DGAT1, and PICALM) regions, and 6 are located in introns of the SLC37A1, MGST1, CSN2, BRI3BP, FASN, and ANKH genes.

Genetic parameters for cheese-making properties and milk composition predicted from mid-infrared spectra in a large data set of Montbéliarde cows.

Cheese-making properties of pressed cooked cheeses (PCC) and soft cheeses (SC) were predicted from mid-infrared (MIR) spectra. The traits that were best predicted by MIR spectra (as determined by comparison with reference measurements) were 3 measures of laboratory cheese yield, 5 coagulation traits, and 1 acidification trait for PCC (initial pH; pH0PPC). Coefficients of determination of these traits ranged between 0.54 and 0.89. These 9 traits as well as milk composition traits (fatty acid, protein, mineral, lactose, and citrate content) were then predicted from 1,100,238 MIR spectra from 126,873 primiparous Montbéliarde cows. Using this data set, we estimated the corresponding genetic parameters of these traits by REML procedures. A univariate or bivariate repeatability animal model was used that included the fixed effects of herd × test day × spectrometer, stage of lactation, and year × month of calving as well as the random additive genetic, permanent environmental, and residual effects. Heritability estimates varied between 0.37 and 0.48 for the 9 cheese-making property traits analyzed. Coagulation traits were the ones with the highest heritability (0.42 to 0.48), whereas cheese yields and pH0 PPC had the lowest heritability (0.37 to 0.39). Strong favorable genetic correlations, with absolute values between 0.64 and 0.97, were found between different measures of cheese yield, between coagulation traits, between cheese yields and coagulation traits, and between coagulation traits measured for PCC and SC. In contrast, the genetic correlations between milk pH0 PPC and CY or coagulation traits were weak (-0.08 to 0.09). The genetic relationships between cheese-making property traits and milk composition were moderate to high. In particular, high levels of proteins, fatty acids, Ca, P, and Mg in milk were associated with better cheese yields and improved coagulation. Proteins in milk were strongly genetically correlated with coagulation traits and, to a lesser extent, with cheese yields, whereas fatty acids in milk were more genetically correlated with cheese yields than with coagulation traits. This study, carried out on a large scale in Montbéliarde cows, shows that MIR predictions of cheese yields and milk coagulation properties are sufficiently accurate to be used for genetic analyses. Cheese-making traits, as predicted from MIR spectra, are moderately heritable and could be integrated into breeding objectives without additional phenotyping cost, thus creating an opportunity for efficient improvement via selection.

Short communication: Genetic parameters for milk protein composition predicted using mid-infrared spectroscopy in the French Montbéliarde, Normande, and Holstein dairy cattle breeds.

Genetic parameters for the major milk proteins were estimated in the 3 main French dairy cattle breeds (i.e. Montbéliarde, Normande, and Holstein) as part of the PhénoFinlait program. The 6 major milk protein contents as well as the total protein content (PC) were estimated from mid-infrared spectrometry on 133,592 test-day milk samples from 20,434 cows in first lactation. Lactation means, expressed as a percentage of milk (protein contents) or of protein (protein fractions), were analyzed with an animal mixed model including fixed environmental effects (herd, year × month of calving, and spectrometer) and a random genetic effect. Genetic parameter estimates were very consistent across breeds. Heritability estimates (h2) were generally higher for protein fractions than for protein contents. They were moderate to high for αS1-casein, αS2-casein, ß-casein, κ-casein, and α-lactalbumin (0.25 < h2 < 0.72). In each breed, ß-lactoglobulin was the most heritable trait (0.61 < h2 < 0.86). Genetic correlations (rg) varied depending on how the percentage was expressed. The PC was strongly positively correlated with protein contents but almost genetically independent from protein fractions. Protein fractions were generally in opposition, except between κ-casein and α-lactalbumin (0.39 < rg < 0.46) and κ-casein and αS2-casein (0.36 < rg < 0.49). Between protein contents, rg estimates were positive, with highest values found between caseins (0.83 < rg < 0.98). In the 3 breeds, ß-lactoglobulin was negatively correlated with caseins (-0.75 < rg < -0.08), in particular with κ-casein (-0.75 < rg < -0.55). These results, obtained from a large panel of cows of the 3 main French dairy cattle breeds, show that routinely collected mid-infrared spectra could be used to modify milk protein composition by selection.

Whole-genome scan to detect quantitative trait loci associated with milk protein composition in 3 French dairy cattle breeds.

In the context of the PhénoFinLait project, a genome-wide analysis was performed to detect quantitative trait loci (QTL) that affect milk protein composition estimated using mid-infrared spectrometry in the Montbéliarde (MO), Normande (NO), and Holstein (HO) French dairy cattle breeds. The 6 main milk proteins (α-lactalbumin, ß-lactoglobulin, and αS1-, αS2-, ß-, and κ-caseins) expressed as grams per 100g of milk (% of milk) or as grams per 100g of protein (% of protein) were estimated in 848,068 test-day milk samples from 156,660 cows. Genotyping was performed for 2,773 MO, 2,673 NO, and 2,208 HO cows using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). Individual test-day records were adjusted for environmental effects and then averaged per cow to define the phenotypes analyzed. Quantitative trait loci detection was performed within each breed using a linkage disequilibrium and linkage analysis approach. A total of 39 genomic regions distributed on 20 of the 29 Bos taurus autosomes (BTA) were significantly associated with milk protein composition at a genome-wide level of significance in at least 1 of the 3 breeds. The 9 most significant QTL were located on BTA2 (133 Mbp), BTA6 (38, 47, and 87 Mbp), BTA11 (103 Mbp), BTA14 (1.8 Mbp), BTA20 (32 and 58 Mbp), and BTA29 (8 Mbp). The BTA6 (87 Mbp), BTA11, and BTA20 (58 Mbp) QTL were found in all 3 breeds, and they had highly significant effects on κ-casein, ß-lactoglobulin, and α-lactalbumin, expressed as a percentage of protein, respectively. Each of these QTL explained between 13% (BTA14) and 51% (BTA11) of the genetic variance of the trait. Many other QTL regions were also identified in at least one breed. They were located on 14 additional chromosomes (1, 3, 4, 5, 7, 15, 17, 19, 21, 22, 24, 25, 26, and 27), and they explained 2 to 8% of the genetic variance of 1 or more protein composition traits. Concordance analyses, performed between QTL status and sequence-derived polymorphisms from 13 bulls, revealed previously known causal polymorphisms in LGB (BTA11) and GHR (BTA20 at 32 Mbp) and excluded some other previously described mutations. These results constitute a first step in identifying causal mutations and using routinely collected mid-infrared predictions in future genomic selection programs to improve bovine milk protein composition.

Review: Towards the agroecological management of ruminants, pigs and poultry through the development of sustainable breeding programmes. II. Breeding strategies.

Agroecology uses ecological processes and local resources rather than chemical inputs to develop productive and resilient livestock and crop production systems. In this context, breeding innovations are necessary to obtain animals that are both productive and adapted to a broad range of local contexts and diversity of systems. Breeding strategies to promote agroecological systems are similar for different animal species. However, current practices differ regarding the breeding of ruminants, pigs and poultry. Ruminant breeding is still an open system where farmers continue to choose their own breeds and strategies. Conversely, pig and poultry breeding is more or less the exclusive domain of international breeding companies which supply farmers with hybrid animals. Innovations in breeding strategies must therefore be adapted to the different species. In developed countries, reorienting current breeding programmes seems to be more effective than developing programmes dedicated to agroecological systems that will struggle to be really effective because of the small size of the populations currently concerned by such systems. Particular attention needs to be paid to determining the respective usefulness of cross-breeding v. straight breeding strategies of well-adapted local breeds. While cross-breeding may offer some immediate benefits in terms of improving certain traits that enable the animals to adapt well to local environmental conditions, it may be difficult to sustain these benefits in the longer term and could also induce an important loss of genetic diversity if the initial pure-bred populations are no longer produced. As well as supporting the value of within-breed diversity, we must preserve between-breed diversity in order to maintain numerous options for adaptation to a variety of production environments and contexts. This may involve specific public policies to maintain and characterize local breeds (in terms of both phenotypes and genotypes), which could be used more effectively if they benefited from the scientific and technical resources currently available for more common breeds. Last but not least, public policies need to enable improved information concerning the genetic resources and breeding tools available for the agroecological management of livestock production systems, and facilitate its assimilation by farmers and farm technicians.

Review: Towards the agroecological management of ruminants, pigs and poultry through the development of sustainable breeding programmes: I-selection goals and criteria.

Agroecology uses natural processes and local resources rather than chemical inputs to ensure production while limiting the environmental footprint of livestock and crop production systems. Selecting to achieve a maximization of target production criteria has long proved detrimental to fitness traits. However, since the 1990s, developments in animal breeding have also focussed on animal robustness by balancing production and functional traits within overall breeding goals. We discuss here how an agroecological perspective should further shift breeding goals towards functional traits rather than production traits. Breeding for robustness aims to promote individual adaptive capacities by considering diverse selection criteria which include reproduction, animal health and welfare, and adaptation to rough feed resources, a warm climate or fluctuating environmental conditions. It requires the consideration of genotype×environment interactions in the prediction of breeding values. Animal performance must be evaluated in low-input systems in order to select those animals that are adapted to limiting conditions, including feed and water availability, climate variations and diseases. Finally, we argue that there is no single agroecological animal type, but animals with a variety of profiles that can meet the expectations of agroecology. The standardization of both animals and breeding conditions indeed appears contradictory to the agroecological paradigm that calls for an adaptation of animals to local opportunities and constraints in weakly artificialized systems tied to their physical environment.

Prediction of fatty acid profiles in cow, ewe, and goat milk by mid-infrared spectrometry.

Mid-infrared (MIR) spectrometry was used to estimate the fatty acid (FA) composition in cow, ewe, and goat milk. The objectives were to compare different statistical approaches with wavelength selection to predict the milk FA composition from MIR spectra, and to develop equations for FA in cow, goat, and ewe milk. In total, a set of 349 cow milk samples, 200 ewe milk samples, and 332 goat milk samples were both analyzed by MIR and by gas chromatography, the reference method. A broad FA variability was ensured by using milk from different breeds and feeding systems. The methods studied were partial least squares regression (PLS), first-derivative pretreatment + PLS, genetic algorithm + PLS, wavelets + PLS, least absolute shrinkage and selection operator method (LASSO), and elastic net. The best results were obtained with PLS, genetic algorithm + PLS and first derivative + PLS. The residual standard deviation and the coefficient of determination in external validation were used to characterize the equations and to retain the best for each FA in each species. In all cases, the predictions were of better quality for FA found at medium to high concentrations (i.e., for saturated FA and some monounsaturated FA with a coefficient of determination in external validation >0.90). The conversion of the FA expressed in grams per 100mL of milk to grams per 100g of FA was possible with a small loss of accuracy for some FA.

Evolution of the genetic variability of eight French dairy cattle breeds assessed by pedigree analysis.

A pedigree analysis was performed on eight French dairy cattle breeds to assess their change in genetic variability since a first analysis completed in 1996. The Holstein, Normande and Montbéliarde breeds are selected internationally with over hundreds of thousands cows registered in the performance recording system. Three breeds are internationally selected but with limited numbers of cows in France (Brown Swiss, French Simmental and French Red Pied). The last two remaining breeds (Abondance and Tarentaise) are raised at regional level. The effective numbers of ancestors of cows born between 2004 and 2007 varied between 15 (Abondance and Tarentaise) and 51 (French Red Pied). The effective population sizes (classical approach) varied between 53 (Abondance) and 197 (French Red Pied). This article also compares the genetic variability of the ex situ (collections of the French National Cryobank) and in situ populations. The results were commented in regard to the recent history of gene flows in the different breeds as well as the existence of more or less stringent bottlenecks. Our results showed that whatever the size of the breeds, their genetic diversity impoverished quite rapidly since 1996 and they all could be considered as quite poor from a genetic diversity point of view. It shows the need for setting up cryobanks as gene reservoirs as well as sustainable breeding programmes that include loss of genetic diversity as an integrated control parameter.

New phenotypes for new breeding goals in dairy cattle.

Cattle production faces new challenges regarding sustainability with its three pillars - economic, societal and environmental. The following three main factors will drive dairy cattle selection in the future: (1) During a long period, intensive selection for enhanced productivity has deteriorated most functional traits, some reaching a critical point and needing to be restored. This is especially the case for the Holstein breed and for female fertility, mastitis resistance, longevity and metabolic diseases. (2) Genomic selection offers two new opportunities: as the potential genetic gain can be almost doubled, more traits can be efficiently selected; phenotype recording can be decoupled from selection and limited to several thousand animals. (3) Additional information from other traits can be used, either from existing traditional recording systems at the farm level or from the recent and rapid development of new technologies and precision farming. Milk composition (i.e. mainly fatty acids) should be adapted to better meet human nutritional requirements. Fatty acids can be measured through a new interpretation of the usual medium infrared spectra. Milk composition can also provide additional information about reproduction and health. Modern milk recorders also provide new information, that is, on milking speed or on the shape of milking curves. Electronic devices measuring physiological or activity parameters can predict physiological status like estrus or diseases, and can record behavioral traits. Slaughterhouse data may permit effective selection on carcass traits. Efficient observatories should be set up for early detection of new emerging genetic defects. In the near future, social acceptance of cattle production could depend on its capacity to decrease its ecological footprint. The first solution consists in increasing survival and longevity to reduce replacement needs and the number of nonproductive animals. At the individual level, selection on rumen activity may lead to decreased methane production and concomitantly to improved feed efficiency. A major effort should be dedicated to this new field of research and particularly to rumen flora metagenomics. Low input in cattle production is very important and tomorrow's cow will need to adapt to a less intensive production environment, particularly lower feed quality and limited care. Finally, global climate change will increase pathogen pressure, thus more accurate predictors for disease resistance will be required.

Posttraumatic retroperitoneal rupture of the right colon simulating a retroperitoneal hematoma.

OBJECTIVE: This case illustrates the diagnostic problems encountered in a patient with posttraumatic retroperitoneal abscess caused by perforation of the posterior wall of the cecum, simulating a retroperitoneal hematoma. Because standard diagnostic techniques failed to make early diagnosis, delayed laparotomy and right colectomy with primary repair were performed. The mechanism of the lesion is uncertain but could be a compressive force and direct injury to the cecum by the seat belt. CONCLUSION: Blunt colonic injuries are rare and difficult to diagnose. Septic signs are unexpected in case of posttraumatic retroperitoneal hematoma and should suggest the diagnosis of retroperitoneal colonic perforation.

Extracorporeal shock-wave lithotripsy to remove calcified ureteral stents.

A patient was seen with a large calcification of the renal end of a silicone catheter placed to intubate a cutaneous ureterostomy. Because of the stone, withdrawal of the catheter was impossible, and the patient presented with obstruction and dilatation of the renal cavities along with febrile bacteriuria and renal failure. Extracorporeal shock-wave lithotripsy, done under intravenous sedation, was found to be an effective noninvasive method to treat such a complication of long-term urinary drainage.

Genitourinary tumors and HIV1 infection.

4 patients with solid genitourinary tumors and HIV1 infection have been treated in our institution over the last 2 years. Two patients had seminoma, 1 renal adenocarcinoma and 1 renal angiosarcoma. All had deeply impaired immunity with a low CD4 level. 3 had or developed a true AIDS syndrome according to the WHO and CDC criterias of 1988. The remaining patient was seropositive and died less than 3 months following the diagnosis of renal angiosarcoma. He is the first reported case of renal sarcoma in a patient infected with HIV1. 2 patients were homosexuals, and the 2 others were drug addicts. Along with other reported cases, our cases underline the association between the depression of immunity due to HIV and the onset of solid genitourinary tumors.

[Does rectal examination modify the blood level of specific prostatic antigen? A study of 40 cases]. / Le toucher rectal modifie-t-il le taux sérique de l'antigène prostatique spécifique? Etude sur quarante cas.

Prostatic specific antigen has become an essential laboratory parameter in prostatic cancer; it may rise transiently after various manipulations of prostatic tissue. We decided to investigate a possible modification in PSA after rectal examination. The PSA level, studied before and after rectal examination in 40 patients, confirmed the almost constant rise in PSA after thorough rectal examination. The biokinetic features of PSA are also discussed as they are important to determine the time of PSA assay after a transient rise.

[Urogenital tumors and HIV-1 infection]. / Tumeur urogénitale et infection à HIV 1.

Four patients with solid genito-urinary tumors and HIV 1 infection have been treated in our institution over the last 2 years, including 2 with seminoma, 1 with renal adenocarcinoma and 1 with renal angiosarcoma. All had severely impaired immunity with a low CD4 level. Three had or developed a true AIDS syndrome according to the WHO and CDC criteria (1988). The remaining patient was seropositive and died less than 3 months following the diagnosis of renal angiosarcoma, he is the first reported case of renal sarcoma in a patient infected with HIV 1. Two patients were homosexuals and the other 2 were drug addicts. Along with other reported cases, our cases may underline the association between depression of immunity due to HIV and onset of solid genito-urinary tumors.

Splenectomy performed upon thirty-seven patients with hairy cell leukemia.

Thirty-seven patients with hairy cell leukemia underwent splenectomy. The postoperative course was uneventful for 34 patients. Improvement of peripheral cytopenia was obtained in the majority of patients. Survival time of patients who underwent splenectomy was significantly longer than for patients who did not undergo this procedure. Splenectomy is a habitually effective form of treatment for hairy cell leukemia, although not completely free of risks.