Mathematical modelling of magnetoencephalographic data

Heethaar, R.M. [Promotor]Munck, J.C. de [Copromotor

Effects of data structure on the estimation of covariance functions to describe genotype by environment interactions in a reaction norm model

Covariance functions have been proposed to predict breeding values and genetic (co)variances as a function of phenotypic within herd-year averages (environmental parameters) to include genotype by environment interaction. The objective of this paper was to investigate the influence of definition of environmental parameters and non-random use of sires on expected breeding values and estimated genetic variances across environments. Breeding values were simulated as a linear function of simulated herd effects. The definition of environmental parameters hardly influenced the results. In situations with random use of sires, estimated genetic correlations between the trait expressed in different environments were 0.93, 0.93 and 0.97 while simulated at 0.89 and estimated genetic variances deviated up to 30% from the simulated values. Non random use of sires, poor genetic connectedness and small herd size had a large impact on the estimated covariance functions, expected breeding values and calculated environmental parameters. Estimated genetic correlations between a trait expressed in different environments were biased upwards and breeding values were more biased when genetic connectedness became poorer and herd composition more diverse. The best possible solution at this stage is to use environmental parameters combining large numbers of animals per herd, while losing some information on genotype by environment interaction in the data

Inbreeding depression due to recent and ancient inbreeding in Dutch Holstein–Friesian dairy cattle

International audienceBackground : Inbreeding decreases animal performance (inbreeding depression), but not all inbreeding is expected to be equally harmful. Recent inbreeding is expected to be more harmful than ancient inbreeding, because selection decreases the frequency of deleterious alleles over time. Selection efficiency is increased by inbreeding, a process called purging. Our objective was to investigate effects of recent and ancient inbreeding on yield, fertility and udder health traits in Dutch Holstein–Friesian cows.Methods : In total, 38,792 first-parity cows were included. Pedigree inbreeding ( FPED ) was computed and 75 k geno-type data were used to compute genomic inbreeding, among others based on regions of homozygosity (ROH) in the genome ( FROH).Results : Inbreeding depression was observed, e.g. a 1% increase in FROH was associated with a 36.3 kg (SE = 2.4) decrease in 305-day milk yield, a 0.48 day (SE =0.15) increase in calving interval and a 0.86 unit (SE =0.28) increase in somatic cell score for day 150 through to 400. These effects equalled −0.45, 0.12 and 0.05% of the trait means, respec-tively. When FPED was split into generation-based components, inbreeding on recent generations was more harmful than inbreeding on more distant generations for yield traits. When FPED was split into new and ancestral components, based on whether alleles were identical-by-descent for the first time or not, new inbreeding was more harmful than ancestral inbreeding, especially for yield traits. For example, a 1% increase in new inbreeding was associated with a 2.42 kg (SE =0.41) decrease in 305-day fat yield, compared to a 0.03 kg (SE =0.71) increase for ancestral inbreeding. There were no clear differences between effects of long ROH (recent inbreeding) and short ROH (ancient inbreeding).Conclusions : Inbreeding depression was observed for yield, fertility and udder health traits. For yield traits and based on pedigree, inbreeding on recent generations was more harmful than inbreeding on distant generations and there was evidence of purging. Across all traits, long and short ROH contributed to inbreeding depression. In future work, inbreeding depression and purging should be assessed in more detail at the genomic level, using higher density information and genomic time series

Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.</p&gt

Trends in genome-wide and region-specific genetic diversity in the Dutch-Flemish Holstein-Friesian breeding program from 1986 to 2015

Background: In recent decades, Holstein-Friesian (HF) selection schemes have undergone profound changes, including the introduction of optimal contribution selection (OCS; around 2000), a major shift in breeding goal composition (around 2000) and the implementation of genomic selection (GS; around 2010). These changes are expected to have influenced genetic diversity trends. Our aim was to evaluate genome-wide and region-specific diversity in HF artificial insemination (AI) bulls in the Dutch-Flemish breeding program from 1986 to 2015. Methods: Pedigree and genotype data (~ 75.5 k) of 6280 AI-bulls were used to estimate rates of genome-wide inbreeding and kinship and corresponding effective population sizes. Region-specific inbreeding trends were evaluated using regions of homozygosity (ROH). Changes in observed allele frequencies were compared to those expected under pure drift to identify putative regions under selection. We also investigated the direction of changes in allele frequency over time. Results: Effective population size estimates for the 1986-2015 period ranged from 69 to 102. Two major breakpoints were observed in genome-wide inbreeding and kinship trends. Around 2000, inbreeding and kinship levels temporarily dropped. From 2010 onwards, they steeply increased, with pedigree-based, ROH-based and marker-based inbreeding rates as high as 1.8, 2.1 and 2.8% per generation, respectively. Accumulation of inbreeding varied substantially across the genome. A considerable fraction of markers showed changes in allele frequency that were greater than expected under pure drift. Putative selected regions harboured many quantitative trait loci (QTL) associated to a wide range of traits. In consecutive 5-year periods, allele frequencies changed more often in the same direction than in opposite directions, except when comparing the 1996-2000 and 2001-2005 periods. Conclusions: Genome-wide and region-specific diversity trends reflect major changes in the Dutch-Flemish HF breeding program. Introduction of OCS and the shift in breeding goal were followed by a drop in inbreeding and kinship and a shift in the direction of changes in allele frequency. After introduction of GS, rates of inbreeding and kinship increased substantially while allele frequencies continued to change in the same direction as before GS. These results provide insight in the effect of breeding practices on genomic diversity and emphasize the need for efficient management of genetic diversity in GS schemes.</p

Genetic parameters for social effects on survival in cannibalistic layers: Combining survival analysis and a linear animal model

<p>Abstract</p> <p>Background</p> <p>Mortality due to cannibalism in laying hens is a difficult trait to improve genetically, because censoring is high (animals still alive at the end of the testing period) and it may depend on both the individual itself and the behaviour of its group members, so-called associative effects (social interactions). To analyse survival data, survival analysis can be used. However, it is not possible to include associative effects in the current software for survival analysis. A solution could be to combine survival analysis and a linear animal model including associative effects. This paper presents a two-step approach (2STEP), combining survival analysis and a linear animal model including associative effects (LAM).</p> <p>Methods</p> <p>Data of three purebred White Leghorn layer lines from Institut de Sélection Animale B.V., a Hendrix Genetics company, were used in this study. For the statistical analysis, survival data on 16,780 hens kept in four-bird cages with intact beaks were used. Genetic parameters for direct and associative effects on survival time were estimated using 2STEP. Cross validation was used to compare 2STEP with LAM. LAM was applied directly to estimate genetic parameters for social effects on observed survival days.</p> <p>Results</p> <p>Using 2STEP, total heritable variance, including both direct and associative genetic effects, expressed as the proportion of phenotypic variance, ranged from 32% to 64%. These results were substantially larger than when using LAM. However, cross validation showed that 2STEP gave approximately the same survival curves and rank correlations as LAM. Furthermore, cross validation showed that selection based on both direct and associative genetic effects, using either 2STEP or LAM, gave the best prediction of survival time.</p> <p>Conclusion</p> <p>It can be concluded that 2STEP can be used to estimate genetic parameters for direct and associative effects on survival time in laying hens. Using 2STEP increased the heritable variance in survival time. Cross validation showed that social genetic effects contribute to a large difference in survival days between two extreme groups. Genetic selection targeting both direct and associative effects is expected to reduce mortality due to cannibalism in laying hens.</p

Effects of ocean acidification on invertebrate settlement at volcanic CO<inf>2</inf> vents

We present the first study of the effects of ocean acidification on settlement of benthic invertebrates and microfauna. Artificial collectors were placed for 1 month along pH gradients at CO2 vents off Ischia (Tyrrhenian Sea, Italy). Seventy-nine taxa were identified from six main taxonomic groups (foraminiferans, nematodes, polychaetes, molluscs, crustaceans and chaetognaths). Calcareous foraminiferans, serpulid polychaetes, gastropods and bivalves showed highly significant reductions in recruitment to the collectors as pCO2 rose from normal (336-341 ppm, pH 8.09-8.15) to high levels (886-5,148 ppm) causing acidified conditions near the vents (pH 7.08-7.79). Only the syllid polychaete Syllis prolifera had higher abundances at the most acidified station, although a wide range of polychaetes and small crustaceans was able to settle and survive under these conditions. A few taxa (Amphiglena mediterranea, Leptochelia dubia, Caprella acanthifera) were particularly abundant at stations acidified by intermediate amounts of CO2 (pH 7. 41-7.99). These results show that increased levels of CO2 can profoundly affect the settlement of a wide range of benthic organisms. © 2010 Springer-Verlag