Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species.

In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci. Moreover, we demonstrate that the emergence of recessive genetic defects can be monitored by detecting de novo deleterious mutations in the genome of bulls used for artificial insemination. These results demonstrate the attractiveness of cattle as a model species in the post genomic era, particularly to confirm the genetic aetiology of isolated clinical case reports in humans.

Carcass traits of young bulls in dual-purpose cattle: genetic parameters and genetic correlations with veal calf, type and production traits.

The profitability of dual-purpose breeding farms can be increased through genetic improvement of carcass traits. To develop a genetic evaluation of carcass traits of young bulls, breed-specific genetic parameters were estimated in three French dual-purpose breeds. Genetic correlations between these traits and veal calf, type and milk production traits were also estimated. Slaughter performances of 156 226 Montbeliarde, 160 361 Normande and 8691 Simmental young bulls were analyzed with a multitrait animal model. In the three breeds, heritabilities were moderate for carcass weight (0.12 to 0.19±0.01 to 0.04) and carcass conformation (0.21 to 0.26±0.01 to 0.04) and slightly lower for age at slaughter (0.08 to 0.17±0.01 to 0.03). For all three breeds, genetic correlations between carcass weight and carcass conformation were moderate and favorable (0.30 to 0.52±0.03 to 0.13). They were strong and favorable (-0.49 to -0.71±0.05 to 0.15) between carcass weight and age at slaughter. Between age at slaughter and carcass conformation, they were low and unfavorable to moderate and favorable (-0.25 to 0.10±0.06 to 0.18). Heavier young bulls tend to be better conformed and slaughtered earlier. Genetic correlations between corresponding young bulls and veal production traits were moderate and favorable (0.32 to 0.70±0.03 to 0.09), implying that selecting sires for veal calf production leads to select sires producing better young bulls. Genetic correlations between young bull carcass weight and cow size were moderately favorable (0.22 to 0.45±0.04 to 0.10). Young bull carcass conformation had moderate and favorable genetic correlations (0.11 to 0.24±0.04 to 0.10) with cow width but moderate and unfavorable genetic correlations (-0.21 to -0.36±0.03 to 0.08) with cow height. Taller cows tended to produce heavier young bulls and thinner cows to produce less conformed ones. Genetic correlations between carcass traits of young bulls and cow muscularity traits were low to moderate and favorable. Finally, genetic correlations between carcass traits of young bulls and milk production traits were low and unfavorable to moderate and favorable. These results indicate the existence for all three breeds of genetic variability for the genetic improvement of carcass traits of young bulls as well as favorable genetic correlations for their simultaneous selection and no strong unfavorable correlation with milk production traits.

Phenotypic and genetic relationships between growth and feed intake curves and feed efficiency and amino acid requirements in the growing pig.

Improvement of feed efficiency in pigs has been achieved essentially by increasing lean growth rate, which resulted in lower feed intake (FI). The objective was to evaluate the impact of strategies for improving feed efficiency on the dynamics of FI and growth in growing pigs to revisit nutrient recommendations and strategies for feed efficiency improvement. In 2010, three BWs, at 35±2, 63±9 and 107±7 kg, and daily FI during this period were recorded in three French test stations on 379 Large White and 327 French Landrace from maternal pig populations and 215 Large White from a sire population. Individual growth and FI model parameters were obtained with the InraPorc® software and individual nutrient requirements were computed. The model parameters were explored according to feed efficiency as measured by residual feed intake (RFI) or feed conversion ratio (FCR). Animals were separated in groups of better feed efficiency (RFI- or FCR-), medium feed efficiency and poor feed efficiency. Second, genetic relationships between feed efficiency and model parameters were estimated. Despite similar average daily gains (ADG) during the test for all RFI groups, RFI- pigs had a lower initial growth rate and a higher final growth rate compared with other pigs. The same initial growth rate was found for all FCR groups, but FCR- pigs had significantly higher final growth rates than other pigs, resulting in significantly different ADG. Dynamic of FI also differed between RFI or FCR groups. The calculated digestible lysine requirements, expressed in g/MJ net energy (NE), showed the same trends for RFI or FCR groups: the average requirements for the 25% most efficient animals were 13% higher than that of the 25% least efficient animals during the whole test, reaching 0.90 to 0.95 g/MJ NE at the beginning of the test, which is slightly greater than usual feed recommendations for growing pigs. Model parameters were moderately heritable (0.30±0.13 to 0.56±0.13), except for the precocity of growth (0.06±0.08). The parameter representing the quantity of feed at 50 kg BW showed a relatively high genetic correlation with RFI (0.49±0.14), and average protein deposition between 35 and 110 kg had the highest correlation with FCR (-0.76±0.08). Thus, growth and FI dynamics may be envisaged as breeding tools to improve feed efficiency. Furthermore, improvement of feed efficiency should be envisaged jointly with new feeding strategies.

Genetic tools to improve reproduction traits in dairy cattle.

Fertility is a major concern in the dairy cattle industry and has been the subject of numerous studies over the past 20 years. Surprisingly, most of these studies focused on rough female phenotypes and, despite their important role in reproductive success, male- and embryo-related traits have been poorly investigated. In recent years, the rapid and important evolution of technologies in genetic research has led to the development of genomic selection. The generalisation of this method in combination with the achievements of the AI industry have led to the constitution of large databases of genotyping and sequencing data, as well as refined phenotypes and pedigree records. These resources offer unprecedented opportunities in terms of fundamental and applied research. Here we present five such examples with a focus on reproduction-related traits: (1) detection of quantitative trait loci (QTL) for male fertility and semen quality traits; (2) detection of QTL for refined phenotypes associated with female fertility; (3) identification of recessive embryonic lethal mutations by depletion of homozygous haplotypes; (4) identification of recessive embryonic lethal mutations by mining whole-genome sequencing data; and (5) the contribution of high-density single nucleotide polymorphism chips, whole-genome sequencing and imputation to increasing the power of QTL detection methods and to the identification of causal variants.

Genomic prediction in French Charolais beef cattle using high-density single nucleotide polymorphism markers.

The objective of the study was to develop a genomic evaluation for French beef cattle breeds and assess accuracy and bias of prediction for different genomic selection strategies. Based on a reference population of 2,682 Charolais bulls and cows, genotyped or imputed to a high-density SNP panel (777K SNP), we tested the influence of different statistical methods, marker densities (50K versus 777K), and training population sizes and structures on the quality of predictions. Four different training sets containing up to 1,979 animals and a unique validation set of 703 young bulls only known on their individual performances were formed. BayesC method had the largest average accuracy compared to genomic BLUP or pedigree-based BLUP. No gain of accuracy was observed when increasing the density of markers from 50K to 777K. For a BayesC model and 777K SNP panels, the accuracy calculated as the correlation between genomic predictions and deregressed EBV (DEBV) divided by the square root of heritability was 0.42 for birth weight, 0.34 for calving ease, 0.45 for weaning weight, 0.52 for muscular development, and 0.27 for skeletal development. Half of the training set constituted animals having only their own performance recorded, whose contribution only represented 5% of the accuracy. Using DEBV as a response brought greater accuracy than using EBV (+5% on average). Considering a residual polygenic component strongly reduced bias for most of the traits. The optimal percentage of polygenic variance varied across traits. Among the methodologies tested to implement genomic selection in the French Charolais beef cattle population, the most accurate and less biased methodology was to analyze DEBV under a BayesC strategy and a residual polygenic component approach. With this approach, a 50K SNP panel performed as well as a 777K panel.

Genetics of residual feed intake in growing pigs: Relationships with production traits, and nitrogen and phosphorus excretion traits.

Residual feed intake (RFI) is defined as the difference between the observed ADFI and the ADFI predicted from production and maintenance requirements. The objectives of this study were to evaluate RFI as a selection criterion to improve feed efficiency and its potential to reduce N and P excretion in 4 pig breeds. Data were collected between 2000 and 2009 in French central test stations for 2 dam breeds [French Landrace (LR) and Large White (LWD)], and 2 sire breeds [Large White (LWS) and Piétrain (PP)]. Numbers of recorded pigs were 6407, 10,694, 2342, and 2448 for the LR, LWD, LWS, and PP breeds, respectively. All PP animals were genotyped for the halothane mutation. This data set was used to calculate RFI equations for each of the 4 breeds, and to estimate genetic parameters for RFI together with growth, carcass, and meat quality traits, and N and P excretion during the test period (35 to 110 kg BW). The RFI explained 20.1% in PP, 26.5% in LWS, 27.6% in LWD, and 29.5% in LR of the phenotypic variability of ADFI. The PP breed differed from the others in this respect, probably due to a lower impact of the variation of body composition on ADFI. Heritability estimates of RFI ranged from 0.21 ± 0.03 (LWD) to 0.33 ± 0.06 (PP) depending on the breed. Heritabilities of N and P excretion traits ranged from 0.29 ± 0.06 to 0.40 ± 0.06. The RFI showed positive genetic correlations with feed conversion ratio (FCR) and excretion traits, these correlations being greater in the sire breeds (from 0.57 to 0.86) than in the dam breeds (from 0.38 to 0.53). Compared with FCR, RFI had weaker genetic correlations with carcass composition, growth rate, and excretion traits. Estimates of genetic correlations between FCR and excretion traits were very close to 1 for all breeds. Finally, excretion traits were, at the genetic level, correlated positively with ADFI, negatively with growth rate and carcass leanness, whereas the halothane n mutation in PP was shown to reduce N and P excretion levels. To conclude, new selection indexes including RFI can be envisaged to efficiently disentangle the responses to selection on growth rate and body composition from those on feed efficiency, with favorable impacts on N and P excretions, particularly in sire pig breeds. However, the switch from FCR to RFI in selection indexes should not resolve the genetic antagonism between feed efficiency and meat quality.

Genetic correlations between males, females and castrates for residual feed intake, feed conversion ratio, growth rate and carcass composition traits in Large White growing pigs.

Data were collected in the course of a divergent selection experiment for residual feed intake (RFI) of Large White growing pigs. This data set was used to estimate (i) heritability for RFI and genetic correlations of RFI with growth and carcass traits within the three sexes (male, castrate and female) and (ii) genetic correlations between sexes for these traits. Individual feed intake of animals raised in collective pens was measured by single-place electronic feeders on 1121 males (candidates for selection), 508 females and 535 castrates (sibs of candidates). Variance components were estimated using the REML methodology applied to a multitrait animal model. Estimates of heritability for RFI were 0.16 ± 0.04, 0.16 ± 0.08 and 0.23 ± 0.10 for males, females and castrates, respectively. Estimates of genetic correlations between sexes for homologous traits were not significantly different from 1 (0.88 to 0.99 for RFI, 0.79 to 0.99 for growth traits and 0.65 to 0.99 for carcass composition traits). The relatively low genetic correlations between castrates and males or females for backfat thickness (0.65 and 0.69, respectively) suggest the presence of genotype by sex interactions for this trait.