Vivi Raundahl Gregersen

Preliminary investigation on reliability of genomic estimated breeding values in the Danish Holstein population

This study investigated the reliability of genomic estimated breeding values (GEBV) in the Danish Holstein population. The data in the analysis included 3,330 bulls with both published conventional EBV and single nucleotide polymorphism (SNP) markers. After data editing, 38,134 SNP markers were available. In the analysis, all SNP were fitted simultaneously as random effects in a Bayesian variable selection model, which allows heterogeneous variances for different SNP markers. The response variables were the official EBV. Direct GEBV were calculated as the sum of individual SNP effects. Initial analyses of 4 index traits were carried out to compare models with different intensities of shrinkage for SNP effects; that is, mixture prior distributions of scaling factors (standard deviation of SNP effects) assuming 5, 10, 20, or 50% of SNP having large effects and the others having very small or no effects, and a single prior distribution common for all SNP. It was found that, in general, the model with a common prior distribution of scaling factors had better predictive ability than any mixture prior models. Therefore, a common prior model was used to estimate SNP effects and breeding values for all 18 index traits. Reliability of GEBV was assessed by squared correlation between GEBV and conventional EBV (r(2)(GEBV, EBV)), and expected reliability was obtained from prediction error variance using a 5-fold cross validation. Squared correlations between GEBV and published EBV (without any adjustment) ranged from 0.252 to 0.700, with an average of 0.418. Expected reliabilities ranged from 0.494 to 0.733, with an average of 0.546. Averaged over 18 traits, r(2)(GEBV, EBV) was 0.13 higher and expected reliability was 0.26 higher than reliability of conventional parent average. The results indicate that genomic selection can greatly improve the accuracy of preselection for young bulls compared with traditional selection based on parent average information.

Effectiveness of microsatellite and SNP markers for parentage and identity analysis in species with low genetic diversity: the case of European bison

The European bison (Bison bonasus) has recovered successfully after a severe bottleneck about 90 years ago but has been left with low genetic variability that may substantially hinder parentage and identity analysis. According to pedigree analysis, over 80% of the genes in the contemporary population descend from just two founder animals and inbreeding coefficients averaged almost 0.5, whereas microsatellite heterozygosity does not exceed 0.3. We present a comparison of the effectiveness of 17 microsatellite and 960 single nucleotide polymorphism (SNP) markers for paternity and identity analysis in the European bison. Microsatellite-based paternity and identity analysis was unsuccessful because of low marker heterozygosity and is not a practical approach in this species. Simulations using SNP markers suggest that 80–90 randomly selected loci, or just 50–60 of the most heterozygous loci, would be sufficient to ensure successful paternity and identity analysis in this species. For the purpose of standardizing future analysis, a panel of 50–60 bovine SNPs characterized by high heterozygosity and an even distribution in the genome could be selected. This panel of markers could be typed using VeraCode (Illumina) or similar SNP genotyping systems. The low cost of these SNP genotyping methods compared with a 16 locus microsatellite survey means that off-the-shelf SNP genotyping systems developed for domestic species represent powerful tools for genetic analysis in related species, and can be effective even in bottlenecked species in which heterozygosity of other markers such as microsatellites may be very low.

Genome-wide association scan and phased haplotype construction for quantitative trait loci affecting boar taint in three pig breeds

BackgroundBoar taint is the undesirable smell and taste of pork meat derived from some entire male pigs. The main causes of boar taint are the two compounds androstenone and skatole (3-methyl-indole). The steroid androstenone is a sex pheromone produced in the testis of the boars. Skatole is produced from tryptophan by bacteria in the intestine of the pigs. In many countries pigs are castrated as piglets to avoid boar taint, however, this is undesirable for animal welfare reasons. Genetic variations affecting the level of boar taint have previously been demonstrated in many breeds. In the study presented in this paper, markers and haplotypes, which can be applied to DNA-based selection schemes in order to reduce or eliminate the boar taint problem, are identified.ResultsApproximately 30,000 SNPs segregating in 923 boars from three Danish breeds; Duroc, Landrace, and Yorkshire, were used to conduct genome wide association studies of boar taint compounds. At 46 suggestive quantitative trait loci (QTL), 25 haplotypes and three single markers with effects were identified. Furthermore, 40% of the haplotypes mapped to previously identified regions. Haplotypes were also analysed for effects of slaughter weight and meat content. The most promising haplotype was identified on Sus scrofa chromosome 1. The gain in fixed effect of having this haplotype on level of androstenone in Landrace was identified to be high (1.279 μg/g). In addition, this haplotype explained 16.8% of the phenotypic variation within the trait. The haplotype was identified around the gene CYB5A which is known to have an indirect impact on the amount of androstenone. In addition to CYB5A, the genes SRD5A2, LOC100518755, and CYP21A2 are candidate genes for other haplotypes affecting androstenone, whereas, candidate genes for the indolic compounds were identified to be SULT1A1 and CYP2E1.ConclusionsDespite the small sample size, a total of 25 haplotypes and three single markers were identified including genomic regions not previously reported. The haplotypes that were analysed showed large effects on trait level. However, little overlap of QTL between breeds was observed.

Quantitative trait loci analysis of swine meat quality traits.

A QTL study was performed in large half-sib families to characterize the genetic background of variation in pork quality traits as well as to examine the possibilities of including QTL in a marker-assisted selection scheme. The quality traits included ultimate pH in LM and the semimembranosus, drip loss, and the Minolta color measurements L*, a*, and b* representing meat lightness, redness, and yellowness, respectively. The families consist of 3,883 progenies of 12 Duroc boars that were evaluated to identify the QTL. The linkage map consists of 462 SNP markers on 18 porcine autosomes. Quantitative trait loci were mapped using a linear mixed model with fixed factors (sire, sex, herd, month, sow age) and random factors (polygenic effect, QTL effects, and litter). Chromosome-wide and genome-wide significance thresholds were determined by Peiphos approach, and 95% Bayes credibility intervals were estimated from a posterior distribution of the QTL position. In total, 31 QTL for the 6 meat quality traits were found to be significant at the 5% chromosome-wide level, among which 11 QTL were significant at the 5% genome-wide level and 5 of these were significant at the 0.1% genome-wide level. Segregation of the identified QTL in different families was also investigated. Most of the identified QTL segregated in 1 or 2 families. For the QTL affecting ultimate pH in LM and semimembranosus and L* and b* value on SSC6, the positions of the QTL and the shapes of the likelihood curves were almost the same. In addition, a strong correlation of the estimated effects of these QTL was found between the 4 traits, indicating that the same genes control these traits. A similar pattern was seen on SSC15 for the QTL affecting ultimate pH in the 2 muscles and drip loss. The results from this study will be helpful for fine mapping and identifying genes affecting meat quality traits, and tightly linked markers may be incorporated into marker-assisted selection programs.

Bovine chromosomal regions affecting rheological traits in acid-induced skim milk gels

The production of fermented milk products has increased worldwide during the last decade and is expected to continue to increase during the coming decade. The quality of these products may be optimized through breeding practices; however, the relations between cow genetics and technological properties of acid milk gels are not fully known. Therefore, the aim of this study was to identify chromosomal regions affecting acid-induced coagulation properties and possible candidate genes. Skim milk samples from 377 Swedish Red cows were rheologically analyzed for acid-induced coagulation properties using low-amplitude oscillation measurements. The resulting traits, including gel strength, coagulation time, and yield stress, were used to conduct a genome-wide association study. Single nucleotide polymorphisms (SNP) were identified using the BovineHD SNPChip (Illumina Inc., San Diego, CA), resulting in almost 621,000 segregating markers. The genome was scanned for putative quantitative trait loci (QTL) regions, haplotypes based on highly associated SNP were inferred, and the additive genetic effects of haplotypes within each QTL region were analyzed using mixed models. A total of 8 genomic regions were identified, with large effects of the significant haplotype explaining between 4.8 and 9.8% of the phenotypic variance of the studied traits. One major QTL was identified to overlap between gel strength and yield stress, the QTL identified with the most significant SNP closest to the gene coding for κ-casein (CSN3). In addition, a chromosome-wide significant region affecting yield stress on BTA 11 was identified to be colocated with PAEP, coding for β-lactoglobulin. Furthermore, the coagulation properties of the genetic variants within the 2 genes were compared with the coagulation properties identified by the patterns of the haplotypes within the regions, and it was discovered that the haplotypes were more diverse and in one case slightly better at explaining the phenotypic variance. Besides these significant QTL comprising the 2 milk proteins, 3 additional genes are proposed as possible candidates, namely RAB22A, CDH13, and STAT1, and all have previously been found to be expressed in the mammary gland. To our knowledge, this is the first attempt to map QTL regions for acid-induced coagulation properties.

Quantitative trait loci analysis of osteochondrosis traits in the elbow joint of pigs.

Osteochondrosis is a growth disorder in the cartilage of young animals and is characterised by lesions found in the cartilage and bone. This study identified quantitative trait loci (QTLs) associated with six osteochondrosis lesion traits in the elbow joint of finishing pigs. The traits were: thickening of the cartilage, lesion in the subchondral bone, irregular cartilage surface, fissure under the cartilage, an irregular sagittal central groove and depression of the proximal edge of the radius. The study comprised 7172 finishing pigs from crossing 12 Duroc boars with 600 crossbred Landrace × Large White sows and included 462 single nucleotide polymorphism markers. The results showed 18 QTLs exceeding the 5% genome-wide threshold. The QTLs associated with lesions in the medial part of the condylus humeri (assumed to be the four main osteochondrosis traits) were, in most cases, at common locations, whereas the QTLs associated with depression of the proximal edge of the radius in general were on the same chromosomes but at separate locations. The detected QTLs explain a large part of the genetic variation, which is promising for incorporating osteochondrosis into a breeding programme using marker-assisted selection.

Depauperate genetic variability detected in the American and European bison using genomic techniques

A total of 929 polymorphic SNPs in EB (out of 54, 000 SNPs screened using a BovineSNP50 Illumina Genotyping BeadChip), and 1, 524 and 1, 403 polymorphic SNPs in WB and PB, respectively, were analysed. EB, WB and PB have all undergone recent drastic reductions in population size. Accordingly, they exhibited extremely depauperate genomes, deviations from genetic equilibrium and a genome organization consisting of a mosaic of haplotype blocks: regions with low haplotype diversity and high levels of linkage disequilibrium. No evidence for positive or stabilizing selection was found in EB, WB and PB, likely reflecting drift overwhelming selection. We suggest that utilization of genome-wide screening technologies, followed by utilization of less expensive techniques (e.g. VeraCode and Fluidigm EP1), holds large potential for genetic monitoring of populations. Additionally, these techniques will allow radical improvements of breeding practices in captive or managed populations, otherwise hampered by the limited availability of polymorphic markers. This result in improved possibilities for 1) estimating genetic relationships among individuals and 2) designing breeding strategies which attempt to preserve or reduce polymorphism in ecologically relevant genes and/or entire blocks.ReviewersThis article was reviewed by: Fyodor Kondrashov and Shamil Sunyaev

Identification of QTL for dorso-caudal chronic pleuritis in 12 crossbred porcine families.

Pleuropneumonia is a major problem in pig production. At the time of slaughter, chronic pleuritis (CP) developed from pleuropneumonia is a common finding, and breeding for a reduced incidence of CP using marker-assisted selection (MAS) would be advantageous. Before applying MAS, quantitative trait loci (QTL) or markers associated with the prevalence of CP should be identified. In this study, 7470 pigs from crosses between 12 Danish Duroc boars and 604 sows (Danish Landrace × Danish Large White) were evaluated for CP located on the dorso-caudal part of the lungs. Quantitative trait loci were identified within boar families using both a Binomial logistic regression method and a chi-square test of association. Significant QTL for CP were detected on Sus scrofa chromosomes (SSC) 2, 8, 12, 13, 14 and 18 using both methods. One QTL on SSC 8 was also detected across families. For the QTL identified within families, the odds-ratio of having CP was approximately twice as high for the unfavourable allele compared to the favourable one. These QTL and closely linked markers show promise for the development of gene-specific markers associated with a reduced incidence of CP located on the dorso-caudal part of the lungs.

Phylogenetic relationships among the European and American bison and seven cattle breeds reconstructed using the BovineSNP50 Illumina Genotyping BeadChip.

Here we present the first attempt to use the BovineSNP50 Illumina Genotyping BeadChip for genome-wide screening of European bison Bison bonasus bonasus (EB), two subspecies of American bison: the plains bison Bison bison bison (PB), the wood bison Bison bison athabascae (WB) and seven cattle Bos taurus breeds. Our aims were to (1) reconstruct their evolutionary relationships, (2) detect any genetic signature of past bottlenecks and to quantify the consequences of bottlenecks on the genetic distances amongst bison subspecies and cattle, and (3) detect loci under positive or stabilizing selection. A Bayesian clustering procedure (STRUCTURE) detected ten genetically distinct clusters, with separation among all seven cattle breeds and European and American bison, but no separation between plain and wood bison. A linkage disequilibrium based program (LDNE) was used to estimate the effective population size (Ne) for the cattle breeds; Ne was generally low, relative to the census size of the breeds (cattle breeds: mean Ne = 299.5, min Ne = 18.1, max Ne = 755.0). BOTTLENECK 1.2 detected signs of population bottlenecks in EB, PB and WB populations (sign test and standardized sign test: p = 0.0001). Evidence for loci under selection was found in cattle but not in bison. All extant wild populations of bison have shown to have survived severe bottlenecks, which has likely had large effects on genetic diversity within and differentiation among groups.

Genomic regions associated with ventro-cranial chronic pleuritis in pig

Ventro-cranial chronic pleuritis can be a result of pleuropneumonia and enzootic pneumonia. These diseases cause severe losses in intensive pig production worldwide, but host resistance is difficult to breed for. It could be beneficial to use marker-assisted selection, and a step towards this is to identify genomic regions associated with the trait. For this purpose, 7304 pigs from 11 boar families were analysed for associations between single nucleotide polymorphisms and ventro-cranial chronic pleuritis. The pigs were genotyped by the use of the iSelect Custom 7 K porcine SNP Chip. Quantitative trait loci (QTL), significant at the chromosome-wide level, were identified on Sus scrofa chromosomes (SSC) 2, 4, 11, 12 and 13 in four different boar families. The QTL on SSC 4 in family G was also significant at the genome-wide threshold according to Bonferroni correction. We have identified a number of candidate genes, but the causative mutations still need to be identified. Markers closely associated with the resistance traits have a strong potential for use in breeding towards animals with improved characteristics concerning ventro-cranial chronic pleuritis.