On the value of the phenotypes in the genomic era

AbstractGenetic improvement programs around the world rely on the collection of accurate phenotypic data. These phenotypes have an inherent value that can be estimated as the contribution of an additional record to genetic gain. Here, the contribution of phenotypes to genetic gain was calculated using traditional progeny testing (PT) and 2 genomic selection (GS) strategies that, for simplicity, included either males or females in the reference population. A procedure to estimate the theoretical economic contribution of a phenotype to a breeding program is described for both GS and PT breeding programs through the increment in genetic gain per unit of increase in estimated breeding value reliability obtained when an additional phenotypic record is added. The main factors affecting the value of a phenotype were the economic value of the trait, the number of phenotypic records already available for the trait, and its heritability. Furthermore, the value of a phenotype was affected by several other factors, including the cost of establishing the breeding program and the cost of phenotyping and genotyping. The cost of achieving a reliability of 0.60 was assessed for different reference populations for GS. Genomic reference populations of more sires with small progeny group sizes (e.g., 20 equivalent daughters) had a lower cost than those reference populations with either large progeny group sizes for fewer genotyped sires, or female reference populations, unless the heritability was large and the cost of phenotyping exceeded a few hundred dollars; then, female reference populations were preferable from an economic perspective

Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-kappa B activation

Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development of neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) has emerged as an anti-inflammatory molecule by inhibiting NF-κB activity in various cell types, but its effect in BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a was upregulated in microvessels of MS-active lesions and the spinal cord of mice with experimental autoimmune encephalomyelitis. In vitro, TNFα and IFNγ treatment of human cerebral microvascular endothelial cells (hCMEC/D3) led to upregulation of miR-146a. Brain endothelial overexpression of miR-146a diminished, whereas knockdown of miR-146a augmented cytokine-stimulated adhesion of T cells to hCMEC/D3 cells, nuclear translocation of NF-κB, and expression of adhesion molecules in hCMEC/D3 cells. Furthermore, brain endothelial miR-146a modulates NF-κB activity upon cytokine activation through targeting two novel signaling transducers, RhoA and nuclear factor of activated T cells 5, as well as molecules previously identified, IL-1 receptor-associated kinase 1, and TNF receptor-associated factor 6. We propose brain endothelial miR-146a as an endogenous NF-κB inhibitor in BECs associated with decreased leukocyte adhesion during neuroinflammation. </p

Use of partial least squares regression to impute SNP genotypes in Italian Cattle breeds

Background The objective of the present study was to test the ability of the partial least squares regression technique to impute genotypes from low density single nucleotide polymorphisms (SNP) panels i.e. 3K or 7K to a high density panel with 50K SNP. No pedigree information was used. Methods Data consisted of 2093 Holstein, 749 Brown Swiss and 479 Simmental bulls genotyped with the Illumina 50K Beadchip. First, a single-breed approach was applied by using only data from Holstein animals. Then, to enlarge the training population, data from the three breeds were combined and a multi-breed analysis was performed. Accuracies of genotypes imputed using the partial least squares regression method were compared with those obtained by using the Beagle software. The impact of genotype imputation on breeding value prediction was evaluated for milk yield, fat content and protein content. Results In the single-breed approach, the accuracy of imputation using partial least squares regression was around 90 and 94% for the 3K and 7K platforms, respectively; corresponding accuracies obtained with Beagle were around 85% and 90%. Moreover, computing time required by the partial least squares regression method was on average around 10 times lower than computing time required by Beagle. Using the partial least squares regression method in the multi-breed resulted in lower imputation accuracies than using single-breed data. The impact of the SNP-genotype imputation on the accuracy of direct genomic breeding values was small. The correlation between estimates of genetic merit obtained by using imputed versus actual genotypes was around 0.96 for the 7K chip. Conclusions Results of the present work suggested that the partial least squares regression imputation method could be useful to impute SNP genotypes when pedigree information is not available

Design of a Bovine Low-Density SNP Array Optimized for Imputation

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle

Paratuberculosis sero-status and milk production, SCC and calving interval in Irish dairy herds

The objective of this study was to investigate the impact of paratuberculosis sero-status on milk yield, fat, protein, somatic cell count and calving interval in Irish dairy herds. Serum from all animals over 12 months of age (n = 2,602) in 34 dairy herds was tested for antibodies to Mycobacterium avium subsp. paratuberculosis using an ELISA. Herds were categorised by sero-status into positive, non-negative and negative, where a positive herd contained two or more positive cows, a non-negative herd contained only one positive cow and a negative herd contained no positive cows. Data at animal, parity and herd-level were analysed by multiple regression using general linear models. Positive herds (mean herd size = 129 cows) and non-negative herds (81 cows) were larger than negative herds (72 cows) (P < 0.01). Negative herds had the highest economic breeding index (EBI), while positive herds had the highest estimated breeding value (EBV) for milk yield. There was no significant effect of paratuberculosis sero-status at animal, parity or herd-level on milk yield, milk fat or protein production, somatic cell count score (SCCS) or calving interval. Negative herds tended to have a lower SCCS than positive and nonnegative herds (P = 0.087). This study only examined the effects of paratuberculosis sero-status but did not examine the clinical effects of Johne's disease at the farm or dairy industry levels

Purging of inbreeding depression within the Irish Holstein-Friesian population

The objective of this study was to investigate whether inbreeding depression in milk production or fertility performance has been partially purged due to selection within the Irish Holstein-Friesian population. Classical, ancestral (i.e., the inbreeding of an individual's ancestors according to two different formulae) and new inbreeding coefficients (i.e., part of the classical inbreeding coefficient that is not accounted for by ancestral inbreeding) were computed for all animals. The effect of each coefficient on 305-day milk, fat and protein yield as well as calving interval, age at first calving and survival to second lactation was investigated. Ancestral inbreeding accounting for all common ancestors in the pedigree had a positive effect on 305-day milk and protein yield, increasing yields by 4.85 kg and 0.12 kg, respectively. However, ancestral inbreeding accounting only for those common ancestors, which contribute to the classical inbreeding coefficient had a negative effect on all milk production traits decreasing 305-day milk, fat and protein yields by -8.85 kg, -0.53 kg and -0.33 kg, respectively. Classical, ancestral and new inbreeding generally had a detrimental effect on fertility and survival traits. From this study, it appears that Irish Holstein-Friesians have purged some of their genetic load for milk production through many years of selection based on production alone, while fertility, which has been less intensely selected for in the population demonstrates no evidence of purging

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

A Validated Genome Wide Association Study to Breed Cattle Adapted to an Environment Altered by Climate Change

Continued production of food in areas predicted to be most affected by climate change, such as dairy farming regions of Australia, will be a major challenge in coming decades. Along with rising temperatures and water shortages, scarcity of inputs such as high energy feeds is predicted. With the motivation of selecting cattle adapted to these changing environments, we conducted a genome wide association study to detect DNA markers (single nucleotide polymorphisms) associated with the sensitivity of milk production to environmental conditions. To do this we combined historical milk production and weather records with dense marker genotypes on dairy sires with many daughters milking across a wide range of production environments in Australia. Markers associated with sensitivity of milk production to feeding level and sensitivity of milk production to temperature humidity index on chromosome nine and twenty nine respectively were validated in two independent populations, one a different breed of cattle. As the extent of linkage disequilibrium across cattle breeds is limited, the underlying causative mutations have been mapped to a small genomic interval containing two promising candidate genes. The validated marker panels we have reported here will aid selection for high milk production under anticipated climate change scenarios, for example selection of sires whose daughters will be most productive at low levels of feeding