Evaluation of the potential use of a meta-population for genomic selection in autochthonous beef cattle populations.

This study investigated the potential application of genomic selection under a multi-breed scheme in the Spanish autochthonous beef cattle populations using a simulation study that replicates the structure of linkage disequilibrium obtained from a sample of 25 triplets of sire/dam/offspring per population and using the BovineHD Beadchip. Purebred and combined reference sets were used for the genomic evaluation and several scenarios of different genetic architecture of the trait were investigated. The single-breed evaluations yielded the highest within-breed accuracies. Across breed accuracies were found low but positive on average confirming the genetic connectedness between the populations. If the same genotyping effort is split in several populations, the accuracies were lower when compared with single-breed evaluation, but showed a small advantage over small-sized purebred reference sets over the accuracies of subsequent generations. Besides, the genetic architecture of the trait did not show any relevant effect on the accuracy with the exception of rare variants, which yielded slightly lower results and higher loss of predictive ability over the generations.

Genomic differentiation between Asturiana de los Valles, Avileña-Negra Ibérica, Bruna dels Pirineus, Morucha, Pirenaica, Retinta and Rubia Gallega cattle breeds.

The Spanish local beef cattle breeds have most likely common origin followed by a process of differentiation. This particular historical evolution has most probably left detectable signatures in the genome. The objective of this study was to identify genomic regions associated with differentiation processes in seven Spanish autochthonous populations (Asturiana de los Valles (AV), Avileña-Negra Ibérica (ANI), Bruna dels Pirineus (BP), Morucha (Mo), Pirenaica (Pi), Retinta (Re) and Rubia Gallega (RG)). The BovineHD 777K BeadChip was used on 342 individuals (AV, n=50; ANI, n=48; BP, n=50; Mo, n=50; Pi, n=48; Re, n=48; RG, n=48) chosen to be as unrelated as possible. We calculated the fixation index (F ST ) and performed a Bayesian analysis named SelEstim. The output of both procedures was very similar, although the Bayesian analysis provided a richer inference and allowed us to calculate significance thresholds by generating a pseudo-observed data set from the estimated posterior distributions. We identified a very large number of genomic regions, but when a very restrictive significance threshold was applied these regions were reduced to only 10. Among them, four regions can be highlighted because they comprised a large number of single nucleotide polymorphisms and showed extremely high signals (Kullback-Leiber divergence (KLD)>6). They are located in BTA 2 (5 575 950 to 10 152 228 base pairs (bp)), BTA 5 (17 596 734 to 18 850 702 bp), BTA 6 (37 853 912 to 39 441 548 bp) and BTA 18 (13 345 515 to 15 243 838 bp) and harbor, among others, the MSTN (Myostatin), KIT-LG (KIT Ligand), LAP3 (leucine aminopeptidase 3), NAPCG (non-SMC condensing I complex, subunit G), LCORL (ligand dependent nuclear receptor corepressor-like) and MC1R (Melanocortin 1 receptor) genes. Knowledge on these genomic regions allows to identify potential targets of recent selection and helps to define potential candidate genes associated with traits of interest, such as coat color, muscle development, fertility, growth, carcass and immunological response.

Bayesian analysis of parent-specific transmission ratio distortion in seven Spanish beef cattle breeds.

Transmission ratio distortion (TRD) is the departure from the expected Mendelian ratio in offspring, a poorly investigated biological phenomenon in livestock species. Given the current availability of specific parametric methods for the analysis of segregation data, this study focused on the screening of TRD in 602 402 single nucleotide polymorphisms covering all autosomal chromosomes in seven Spanish beef cattle breeds. On average, 0.13% (n = 786) and 0.01% (n = 29) of genetic markers evidenced sire- or dam-specific TRD respectively. There were no single nucleotide polymorphisms accounting for both sire- and dam-specific TRD at the same time, and only one marker (rs43147474) accounted for (sire-specific) TRD in all seven breeds. It must be noted that rs43147474 is located in the fourth intronic region of the GTP-binding protein 10 gene, and this locus has been previously linked to the maintenance of mitochondria and nucleolar architectures. Alternatively, other candidate genes surround this hot-spot for sire-specific TRD in the cattle genome, and they are related to embryonic and postnatal lethality as well as prostate cancer, among others. This research characterized the distribution of TRD in the bovine genome, highlighting heterogeneous results when comparing across breeds.

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip.

Linkage disequilibrium (LD) and persistence of phase are fundamental approaches for exploring the genetic basis of economically important traits in cattle, including the identification of QTL for genomic selection and the estimation of effective population size () to determine the size of the training populations. In this study, we have used the Illumina BovineHD chip in 168 trios of 7 Spanish beef cattle breeds to obtain an overview of the magnitude of LD and the persistence of LD phase through the physical distance between markers. Also, we estimated the time of divergence based on the persistence of the LD phase and calculated past from LD estimates using different alternatives to define the recombination rate. Estimates of average (as a measure of LD) for adjacent markers were close to 0.52 in the 7 breeds and decreased with the distance between markers, although in long distances, some LD still remained (0.07 and 0.05 for markers 200 kb and 1 Mb apart, respectively). A panel with a lower boundary of 38,000 SNP would be necessary to launch a successful within-breed genomic selection program. Persistence of phase, measured as the pairwise correlations between estimates of in 2 breeds at short distances (10 kb), was in the 0.89 to 0.94 range and decreased from 0.33 to 0.52 to a range of 0.01 to 0.08 when marker distance increased from 200 kb to 1 Mb, respectively. The magnitude of the persistence of phase between the Spanish beef breeds was similar to those found in dairy breeds. For across-breed genomic selection, the size of the SNP panels must be in the range of 50,000 to 83,000 SNP. Estimates of past showed values ranging from 26 to 31 for 1 generation ago in all breeds. The divergence among breeds occurred between 129 and 207 generations ago. The results of this study are relevant for the future implementation of within- and across-breed genomic selection programs in the Spanish beef cattle populations. Our results suggest that a reduced subset of the SNP panel would be enough to achieve an adequate precision of the genomic predictions.

Genetic diversity and divergence among Spanish beef cattle breeds assessed by a bovine high-density SNP chip.

The availability of SNP chips for massive genotyping has proven to be useful to genetically characterize populations of domestic cattle and to assess their degree of divergence. In this study, the Illumina BovineHD BeadChip genotyping array was used to describe the genetic variability and divergence among 7 important autochthonous Spanish beef cattle breeds. The within-breed genetic diversity, measured as the marker expected heterozygosity, was around 0.30, similar to other European cattle breeds. The analysis of molecular variance revealed that 94.22% of the total variance was explained by differences within individuals whereas only 4.46% was the result of differences among populations. The degree of genetic differentiation was small to moderate as the pairwise fixation index of genetic differentiation among breeds (F) estimates ranged from 0.026 to 0.068 and the Nei's D genetic distances ranged from 0.009 to 0.016. A neighbor joining (N-J) phylogenetic tree showed 2 main groups of breeds: Pirenaica, Bruna dels Pirineus, and Rubia Gallega on the one hand and Avileña-Negra Ibérica, Morucha, and Retinta on the other. In turn, Asturiana de los Valles occupied an independent and intermediate position. A principal component analysis (PCA) applied to a distance matrix based on marker identity by state, in which the first 2 axes explained up to 17.3% of the variance, showed a grouping of animals that was similar to the one observed in the N-J tree. Finally, a cluster analysis for ancestries allowed assigning all the individuals to the breed they belong to, although it revealed some degree of admixture among breeds. Our results indicate large within-breed diversity and a low degree of divergence among the autochthonous Spanish beef cattle breeds studied. Both N-J and PCA groupings fit quite well to the ancestral trunks from which the Spanish beef cattle breeds were supposed to derive.

Monitoring changes in the demographic and genealogical structure of the main Spanish local beef breeds.

Demographic and pedigree analyses describe the structure and dynamics of livestock populations. We studied information recorded in the herdbooks of Asturiana de los Valles (AV; N = 458,806), Avileña-Negra Ibérica (ANI; N = 204,623), Bruna dels Pirineus (BP; N = 62,138), Morucha (Mo; N = 65,350), Pirenaica (Pi; N = 217,428), Retinta (Re; N = 135,300), and Rubia Gallega (RG; N = 235,511) beef breeds from their creation until 2009. All breeds have increased in the number of registered cows in recent years. In all breeds, herds do not behave as isolated entities and a high rate of exchange of breeding males between herds exists. A percentage of herds (12-52%) make some type of selection and sell bulls to other herds. There were large differences in average number of progeny per bull, ranging from 15.6 (AV) to 373.7 animals (RG, with a high incidence of AI). Generation interval estimates ranged from 4.7 (AV) to 7.6 (RG) yr in the sire pathway and from 5.95 (AV) to 7.8 (Mo) yr in the dam pathway. Density of pedigrees varied among breeds, with Pi, ANI, and Re having the more dense pedigrees, with average completeness indexes of more than 96% in the first generation and 80% when 6 generations were considered. A general increase in average inbreeding was observed in all breeds in the years analyzed. For animals born in 2009, average inbreeding coefficients ranged from 0.6 (BP) to 7.2% (Re) when all animals were considered and from 3.6 (Pi) to 17.6% (BP) when only inbred animals were considered. Due to the lack of completeness of pedigrees in most populations, inbreeding coefficients may be considered as a lower bound of the true parameters. The proportion of inbred animals tended to increase in the periods analyzed in all breeds. Differences between inbreeding and coancestry rates (except in RG) suggest the presence of population structure. Effective population size (Ne) based on the inbreeding rate estimated by regression ranged from 43 to 378 for Re and BP, whereas Ne estimates based on coancestry were greater, with a range of 100 for RG to 9,985 for BP. These facts suggest that an adequate mating policy can help to monitor inbreeding so as not to lose genetic variability. Effective number of ancestors in 2009 for 6 of the breeds ranged from 42 (RG) to 220 (AV), with BP having much a greater value, and was lower than was the effective number of founders in all breeds, suggesting the existence of bottlenecks.

Multi-trait and random regression approaches for addressing the wide range of weaning ages in Asturiana de los Valles beef cattle for genetic parameter estimation.

Weaning weight (WW) records of 24,066 Asturiana de los Valles beef cattle, including the progeny of 557 sires and 10,653 dams, were analyzed using a multitrait animal model (MAM) and a random regression model (RRM) in order to estimate the variance components and the breeding value of the animals. Three definitions of WW were used: early weaning (EW) for animals weaned before the age of 180 d; standard weaning (SW) for animals weaned between 180 and 240 d old; and late weaning (LW) for animals weaned between the ages of 240 and 365 d. The heritabilities (h(2)) were high (from 0.49 to 0.63), which fully agrees with previous estimates for this breed. The genetic correlations between EW and SW were 0.86, and lower between EW and LW at 0.543 to 0.622, using MAM and RRM models, respectively. Ranking of sires displayed changes depending on age at weaning of their offspring, which could explain the modest genetic progress reached using MAM evaluation. The first 2 eigenvalues of the random regression coefficient matrix explained 66 and 30% of the genetic variance, which implies important genetic variation underlying the form of the growth curve of the animals during the weaning period. The evaluation of sires according to the official method, as currently carried out by the breeders' association (WW adjusted previously to the age of 180 d), does not exploit the genetic differences in response to their production system where the calf is weaned at variable ages.

Asymptotic variances of QTL estimators with selective DNA pooling.

Investigation on QTL-marker linkage usually requires a great number of observed recombinations, inferred from combined analysis of phenotypes and genotypes. To avoid costly individual genotyping, inferences on QTL position and effects can instead make use of marker allele frequencies. DNA pooling of selected samples makes allele frequency estimation feasible for studies involving large sample sizes. Linkage studies in outbred populations have traditionally exploited half-sib family designs; within the animal production context, half-sibships provide large families that are highly suitable for DNA pooling. Estimators for QTL position and effect have been proposed that make use of information from flanking markers. We present formulas derived by the delta method for the asymptotic variance of these estimators.

Simulating complex traits influenced by genes with fuzzy-valued effects in pedigreed populations.

MOTIVATION: Methods involving fuzzy theory have been rarely applied to genetics. We present an open platform for experimentation with fuzzy numbers as a tool to represent imprecise phenotypes in genetic modeling. RESULTS: A C++ library for simulation of genetic information transmission is introduced. The study of genetic linkage was its first goal, though a design so general as possible has been meant. Fuzzy-valued phenotypes are handled by means of fuzzy numbers. AVAILABILITY: ftp://carleos.etsiig.uniovi.es/pub/falin ftp://fisher.ciencias.uniovi.es/pub/falin ftp://bellman.ciencias.uniovi.es/pub/falin Licensed under the GNU General Public License version 2 (see http://www.gnu.org/licenses/gpl.html).

Genetic parameters for linear udder traits of dairy ewes.

An animal model was used to estimate the repeatabilities and genetic parameters of linear udder traits of Churra ewes (5265 records from 2015 ewes). In addition, the phenotypic correlations were examined between log SCC and udder traits. Heritabilities of udder depth (0.16), udder attachment (0.17), teat placement (0.24), teat size (0.18), and udder shape (0.24) were similar to those for dairy cattle, making it feasible to use data from the proposed linear system in a breeding program to improve the machine milkability of ewes. Genetic correlations among udder traits were generally favorable, implying that selection for improvement of one trait would result in improvement of others. A notable exception was the genetic correlation between teat placement and teat size of 0.62. Vertical placement of teats was associated with larger teats. Also, genetic correlations between udder and yield traits (milk and protein yields) were small, except for udder depth and teat placement. These exceptions predict worsening udder morphology from selection based solely on milk yield. Phenotypic correlations between udder traits and log SCC indicate that present handling routines led to a greater likelihood of infections for deep udders with large teats.

Discharge patterns of neurons in the rostral superior colliculus of cat: activity related to fixation of visual and auditory targets.

Neurons in the rostral superior colliculus (SC) of alert cats exhibit quasi-sustained discharge patterns related to the fixation of visual targets. Because some SC neurons also respond to auditory stimuli, we investigated whether there is a population of neurons in the rostral SC which is active in relation to fixation of both auditory and visual targets. We identified cells which were active with visual fixation and which continued to discharge if the fixation stimulus was briefly extinguished. The population of neurons exhibited similar discharge characteristics when the fixation stimulus was auditory. Few neurons were significantly more active during fixation of visual targets than during fixation of auditory targets. Most fixation neurons showed a diminished discharge rate during spontaneous (self-generated) saccadic eye movements away from a visual fixation stimulus, regardless of the direction of the saccade. This diminished discharge rate (or pause) typically began, on average, 12.2 ms before saccade onset and the duration of the pause was longer than the duration of the saccade. These observations are consistent with the hypothesis that increased discharge of these neurons is related to active fixation and that reductions in their activity are important for the generation of saccades. However, the lack of a precise relationship between pause duration and saccade duration implies that these neurons would be unlikely to project directly to the saccadic burst generator. The mean interval from the beginning of the pauses of fixation neurons to the beginning of the saccades away from fixation targets is also shorter than has been found in brainstem omnipause neurons. By analogy with the concept of a receptive field, a gaze position error field depicts the range of gaze position error for which a cell is active. Although fixation neurons appear to encode the magnitude and direction of the error between visual targets and the visual axis, visual error fields at the end of fixating eye movements were significantly larger than those at stimulus onset. For auditory stimuli, this difference was not significant. These observations are compatible with a number of recent experiments indicating that neural signals of eye position are damped or delayed with respect to current eye position.

Express saccades in cat: effects of task and target modality.

Saccadic eye movements to visual, auditory, and bimodal targets were measured in four adult cats. Bimodal targets were visual and auditory stimuli presented simultaneously at the same location. Three behavioral tasks were used: a fixation task and two saccadic tracking tasks (gap and overlap task). In the fixation task, a sensory stimulus was presented at a randomly selected location, and the saccade to fixate that stimulus was measured. In the gap and overlap tasks, a second target (hereafter called the saccade target) was presented after the cat had fixated the first target. In the gap task, the fixation target was switched off before the saccade target was turned on; in the overlap task, the saccade target was presented before the fixation target was switched off. All tasks required the cats to redirect their gaze toward the target (within a specified degree of accuracy) within 500 ms of target onset, and in all tasks target positions were varied randomly over five possible locations along the horizontal meridian within the cat's oculomotor range. In the gap task, a significantly greater proportion of saccadic reaction times (SRTs) were less than 125 ms, and mean SRTs were significantly shorter than in the fixation task. With visual targets, saccade latencies were significantly shorter in the gap task than in the overlap task, while, with bimodal targets, saccade latencies were similar in the gap and overlap tasks. On the fixation task, SRTs to auditory targets were longer than those to either visual or bimodal targets, but on the gap task, SRTs to auditory targets were shorter than those to visual or bimodal targets. Thus, SRTs reflected an interaction between target modality and task. Because target locations were unpredictable, these results demonstrate that cats, as well as primates, can produce very short latency goal-directed saccades.

Effects of eye position on saccadic eye movements and on the neuronal responses to auditory and visual stimuli in cat superior colliculus.

Many neurons in the deeper layers of the superior colliculus (SC) respond to multiple sensory inputs--visual, auditory, and somatic--as well as provide signals essential for saccadic eye movements to targets in different modalities. When the eyes and pinnae are in primary position, the neural map of auditory space is in rough topographic alignment with the map of visual space, and if the auditory map is based solely on headpinna coordinates, any changes in eye position in the orbit will cause misalignment of the maps. We investigated the effects of eye position on the response of sound-sensitive neurons in the SC of cats because previous work on cats and on monkeys had suggested the possibility of species differences in the representation of auditory signals in the SC. We also investigated the effects of eye position on the accuracy of saccades to auditory, visual, and bimodal stimuli. All studies were conducted in alert, trained cats with the head restrained in a fixed position. Neuronal and behavioral responses were studied during periods when the eyes were steadily directed to different positions relative to the position of the sound. Cats showed partial compensation for eye position in making saccades, regardless of the modality of the target, and they showed similar patterns of error in saccades to auditory and visual targets. These behavioral data are consistent with coding the location of visual and auditory targets in the same coordinate system. In the vast majority of intermediate-layer neurons, eye position significantly affected the number of spikes evoked by sound stimuli. For most of these neurons, changes in eye position produced significant shifts in the speaker location producing maximal response. In some neurons, eye position significantly facilitated the magnitude of neuronal response evoked by sounds from a variety of speaker locations. Because few pinna movements could be detected, in is unlikely that these changes in neuronal response could be due to changes in the position of the pinnae. Our results indicate that the deep layers of the SC contain an eye-centered representation of sound location. Because eye position did not affect the percentage of neurons exhibiting multimodal integration, visual and auditory maps appear to remain integrated in the SC even when the eyes are directed eccentrically.(ABSTRACT TRUNCATED AT 400 WORDS)

Genetic parameters of test day measures for somatic cell count, milk yield, and protein percentage of milking ewes.

Records from monthly test days for milk yield, natural log-transformed SCC, and protein percentage of 10,171 records of 3832 Spanish Churra ewes in 24 herds were analyzed to estimate genetic parameters. Heritabilities and genetic and phenotypic correlations for test day records were estimated using multivariate REML with an animal model, accounting for the effects of litter size, test day within herd group, age at lambing, and month in milk. Heritabilities for test day records of milk, log SCC, and protein percentage were .34, .04, and .13, respectively. Genetic correlations of test day measures of SCC with milk yield and protein percentage were -.37 and .37, respectively; phenotypic correlations were -.05 and .19. Considered as a random effect, test day within herd accounted for 28 and 17% of the total variance of test day milk yield and test day SCC, respectively. The correlation between milk yield and SCC because of the test day within herd, the covariation factor, was estimated to be -.16. Results indicate a moderately high heritability for milk yield, a low heritability for SCC, and moderate, negative genetic relationships between measures of SCC in milk and milk yield.

Factors influencing variation of test day milk yield, somatic cell count, fat, and protein in dairy sheep.

Between January and July 1992, 8403 monthly test day records were obtained from 3202 ewes from 22 Churra dairy flocks in the Castilla-León region of Spain. Variables measured were milk yield, SCC, and fat and protein percentages; means were 912 ml, 1501 x 10(3) cells/ml, 6.76%, and 6.28%. Analysis of variance showed significant effects of flock, stage of lactation, parity, and type of birth on milk yield, SCC, and composition. Variability in SCC among flocks was high and ranged from 420 to 2719 x 10(3) cells/ml. During lactation, SCC and fat and protein percentages showed increases of 31.2, 37.6, and 20.3%. Twin birth ewes had higher SCC (8.6%) and yield (4.4%) than single birth ewes. However, fat and protein fell 1.7 and .8% in twin birth ewes. The parity effect was highly significant for yield, SCC, and fat; first lactation was always lower. A statistical model similar to that for dairy cattle was used to predict milk yield on the basis of flock, ewes within the flock, lactation stage, parity number, type of birth, and SCC. The model predicted 73% of the variation in milk yield.

A defective visual pathway in children with reading disability.

BACKGROUND: The possibility that reading disability in children is associated with visual problems is in dispute. We sought to test the existence of this association by using electrophysiologic techniques to measure the processing of visual information in the magnicellular and parvicellular visual pathways of the brain. METHODS: Visual evoked potentials were measured with scalp electrodes in children 8 to 11 years old who were normal readers and in those with reading disability. The potentials were measured for targets with low (0.5 cycle per degree of visual angle) and high (4.5 cycles per degree) spatial frequency, surrounded by either a steady background or a uniform-field flickering 12 times per second. A flickering field normally reduces the amplitude and increases the latency of a transient potential evoked by a low-spatial-frequency target, which preferentially excites the magnicellular visual pathway, but has little effect on the response to a high-spatial-frequency target. RESULTS: With a steady background, the latencies of the early components (N1 and P1) of the visual evoked potentials were longer in the reading-disabled children than in the normal readers when the low-spatial-frequency target was used, but not when the high-spatial-frequency target was used. In normal readers, the flickering background increased the latency and reduced the amplitude of the early components, whereas in the reading-disabled children only the amplitude was affected. No differences were observed in either group with the high-spatial-frequency target. CONCLUSIONS: The pattern of results suggests that the response of the magnicellular visual pathway is slowed in reading-disabled children, who do not, however, have a general slowing of the visual response. The possibility that there is a cause-and-effect relation between these findings and reading disability will require further study.

Use of the Fossomatic method to determine somatic cell counts in sheep milk.

The Fossomatic method for SCC was compared with the direct microscopic method in 85 half-udder samples of sheep milk. The correlation coefficient was .986. The repeatability of the Fossomatic method showed average variation coefficients less than 5%. The carry-over effect between samples was less than 5%. The effect of the storage method (fresh milk, refrigerated at 4 degrees C and frozen at -19 degrees C) and the sample age were studied in 48 samples of foremilk and strippings. The storage method had a significant effect on the SCC variation. The average fresh, refrigerated, and frozen sample counts were 125,000, 110,000, and 82,000 cells/ml for foremilk and 201,000, 192,000, and 145,000 cells/ml for strippings, respectively. The effect of age on the refrigerated samples was also significant; counts were reduced by about 14% from d 1 to 7 in both types of milk. The effect of age on the frozen sample varied. These results suggest standardization of age and storage conditions of the milk samples to reduce variation of SCC. The milk must not be frozen.

The perceived duration of gratings.

Since visible persistence of grating patterns increases with spatial frequency, it is often inferred that the perceived duration of a grating is also longer at higher spatial frequencies. However, other work has demonstrated that the perceived onset of a grating is also delayed at higher spatial frequencies. Thus it is impossible to infer the subjective duration from the results of visible persistence studies alone. In order to estimate perceived duration in the present study, reaction times (RTs) to grating onsets and offsets were measured for a range of spatial frequencies. The results indicate that although the perceived duration (ie the difference between offset and onset RTs) was consistently longer than the physical duration, the estimates of perceived duration did not vary with changes in spatial frequency. Differences between the present results and earlier findings are interpreted in the context of the different methods used to measure perceived offset.

Electroretinograms and visual evoked potentials in long-term monocularly deprived cats.

The effects of long-term monocular lid-suture deprivation on visual-evoked cortical potentials (VEPs) and flash- and pattern-evoked electroretinograms (FERGs and PERGs, respectively) were assessed in the cat. VEPs were virtually eliminated when recorded with the deprived eye, indicating that the lid suture produced a severe amblyopia in that eye. In contrast, FERGs and PERGs were more similar for both deprived and nondeprived eyes and comparable to those recorded in normal animals. The current findings demonstrate that long-term deprivation (3-4 yr) does not produce systematic changes in the electroretinogram.