Genome wide signatures of positive selection: The comparison of independent samples and the identification of regions associated to traits

<p>Abstract</p> <p>Background</p> <p>The goal of genome wide analyses of polymorphisms is to achieve a better understanding of the link between genotype and phenotype. Part of that goal is to understand the selective forces that have operated on a population.</p> <p>Results</p> <p>In this study we compared the signals of selection, identified through population divergence in the Bovine HapMap project, to those found in an independent sample of cattle from Australia. Evidence for population differentiation across the genome, as measured by F_ST, was highly correlated in the two data sets. Nevertheless, 40% of the variance in F_STbetween the two studies was attributed to the differences in breed composition. Seventy six percent of the variance in F_STwas attributed to differences in SNP composition and density when the same breeds were compared. The difference between F_STof adjacent loci increased rapidly with the increase in distance between SNP, reaching an asymptote after 20 kb. Using 129 SNP that have highly divergent F_STvalues in both data sets, we identified 12 regions that had additive effects on the traits residual feed intake, beef yield or intramuscular fatness measured in the Australian sample. Four of these regions had effects on more than one trait. One of these regions includes the <it>R3HDM1 </it>gene, which is under selection in European humans.</p> <p>Conclusion</p> <p>Firstly, many different populations will be necessary for a full description of selective signatures across the genome, not just a small set of highly divergent populations. Secondly, it is necessary to use the same SNP when comparing the signatures of selection from one study to another. Thirdly, useful signatures of selection can be obtained where many of the groups have only minor genetic differences and may not be clearly separated in a principal component analysis. Fourthly, combining analyses of genome wide selection signatures and genome wide associations to traits helps to define the trait under selection or the population group in which the QTL is likely to be segregating. Finally, the F_STdifference between adjacent loci suggests that 150,000 evenly spaced SNP will be required to study selective signatures in all parts of the bovine genome.</p

Genome wide signatures of positive selection: The comparison of independent samples and the identification of regions associated to traits

The goal of genome wide analyses of polymorphisms is to achieve a better understanding of the link between genotype and phenotype. Part of that goal is to understand the selective forces that have operated on a population

Haplotypes that include the integrin alpha 11 gene are associated with tick burden in cattle

Background: Infestations on cattle by the ectoparasite Boophilus (Rhipicephalus) microplus (cattle tick) impact negatively on animal production systems. Host resistance to tick infestation has a low to moderate heritability in the range 0.13 - 0.64 in Australia. Previous studies identified a QTL on bovine chromosome 10 (BTA10) linked to tick burden in cattle.Results: To confirm these associations, we collected genotypes of 17 SNP from BTA10, including three obtained by sequencing part of the ITGA11 (Integrin alpha 11) gene. Initially, we genotyped 1,055 dairy cattle for the 17 SNP, and then genotyped 557 Brahman and 216 Tropical Composite beef cattle for 11 of the 17 SNP. In total, 7 of the SNP were significantly (P < 0.05) associated with tick burden tested in any of the samples. One SNP, ss161109814, was significantly (P < 0.05) associated with tick burden in both the taurine and the Brahman sample, but the favourable allele was different. Haplotypes for three and for 10 SNP were more significantly (P < 0.001) associated with tick burden than SNP analysed individually. Some of the common haplotypes with the largest sample sizes explained between 1.3% and 1.5% of the residual variance in tick burden.Conclusions: These analyses confirm the location of a QTL affecting tick burden on BTA10 and position it close to the ITGA11 gene. The presence of a significant association in such widely divergent animals suggests that further SNP discovery in this region to detect causal mutations would be warranted

Variation at the Calpain 3 gene is associated with meat tenderness in zebu and composite breeds of cattle

<p>Abstract</p> <p>Background</p> <p>Quantitative Trait Loci (QTL) affecting meat tenderness have been reported on Bovine chromosome 10. Here we examine variation at the Calpain 3 (<it>CAPN3</it>) gene in cattle, a gene located within the confidence interval of the QTL, and which is a positional candidate gene based on the biochemical activity of the protein.</p> <p>Results</p> <p>We identified single nucleotide polymorphisms (SNP) in the genomic sequence of the <it>CAPN3 </it>gene and tested three of these in a sample of 2189 cattle. Of the three SNP genotyped, the <it>CAPN3:c.1538+225G>T </it>had the largest significant additive effect, with an allele substitution effect in the Brahman of <it>α </it>= -0.144 kg, SE = 0.060, <it>P </it>= 0.016, and the polymorphism explained 1.7% of the residual phenotypic variance in that sample of the breed. Significant haplotype substitution effects were found for all three breeds, the Brahman, the Belmont Red, and the Santa Gertrudis. For the common haplotype, the haplotype substitution effect in the Brahman was <it>α </it>= 0.169 kg, SE = 0.056, <it>P </it>= 0.003. The effect of this gene was compared to Calpastatin in the same sample. The SNP show negligible frequencies in taurine breeds and low to moderate minor allele frequencies in zebu or composite animals.</p> <p>Conclusion</p> <p>These associations confirm the location of a QTL for meat tenderness in this region of bovine chromosome 10. SNP in or near this gene may be responsible for part of the overall difference between taurine and zebu breeds in meat tenderness, and the greater variability in meat tenderness found in zebu and composite breeds. The evidence provided so far suggests that none of these tested SNP are causative mutations.</p

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds

status: publishe

Variation at CPE but not CEBPA appears to be associated with intramuscular fat deposition in the longissimus muscle of cattle

An important step in the localisation of quantitative trait loci is the confirmation of trait-marker associations in independent studies. In this report, we test three single nucleotide polymorphisms (SNP) of two genes for associations to intramuscular fat (IMF) measurements in cattle. We genotyped SNP of carboxypeptidase E (CPE) and ccaat/enhancer binding protein, (CEBPA) in a sample of a total of 813 cattle of taurine, composite and indicine breeds. All three polymorphisms showed significant differences between breeds, with the widest range found in CEBPA:g.271A > C where the A allele frequency ranged from P ≤ 0.07 in Brahman to 0.88 in Shorthorn. The taurine breeds showed high linkage disequilibrium between the pair of CPE SNP, with all four breeds showing r ≤ 1.0. The Brahman and Santa Gertrudis showed r ≤ 0.17. Both CPE:g.445C > T and CPE:g.601C > T SNP showed significant allele substitution effects to IMF in animals of taurine ancestry, with an allele substitution effect of ≤ 0.22, P ≤ 0.020 for CPE:g.445C > T, explaining 0.4% of the phenotypic variance

The structure of a cattle stud determined using a medium density single nucleotide polymorphism array

Genetic progress depends on accurate knowledge of the genetic composition of a population or herd including level of inbreeding and parentage. However, in many circumstances, such as at an individual property level, the relationships between animals may be unknown, or at best, only partly known. In this study, we used DNA from 938 animals and genotypes from ~54 000 single nucleotide polymorphisms (SNP) to determine the genetic structure of a stud from Central Queensland. Animals on the study were bred using multi-sire mating in mobs of composite tropically adapted cattle of the Senepol, Belmont and Bonsmara breeds. Following genotyping using an array of 54 000 SNP, we were able to separate animals into breed groups using principal components and show that ~400 SNP were sufficient to separate animals into stable groups if the sample was genetically diverse. However, precise principal component values were only achieved when a few thousand SNP were used. We characterised the pedigree relationships between individuals using a genome relationship matrix. At least 3000 SNP were required to calculate accurate relationship coefficients between individuals. Around 19% of paired comparisons between animals showed similarity equivalent to sharing a great-grandparent or 1/64 shared ancestry. Approximately 8% of the individuals showed more than 10% inbreeding. To demonstrate the utility of calculating the relationship coefficients, we counted the tick burden on each animal at more than one time and then calculated the heritability of tick burden of h2 = 0.46 (±0.08). There was no significant genetic difference in tick burden between Belmont and Bonsmara cattle compared with Senepol on this property once a genetic relationship matrix was included to account for co-ancestry of individuals