second model, the two main conditions were parametrically modulated by the two categories, respectively (SOM, S5.1). The activation of the precuneus was higher for hard dominance-solvable games than for easy ones ( Fig. 4A and table S10). The activation of the insula was higher for the highly focal coordination games than for less focal ones ( Fig. 4B and table S11). Previous studies also found that precuneus activity increased when the number of planned moves increased (40, 41). The higher demand for memory-related imagery and memory retrieval may explain the greater precuneus activation in hard dominance-solvable games. In highly focal coordination games, the participants may have felt quite strongly that the pool students must notice the same salient feature. This may explain why insula activation correlates with NCI.Participants might have disagreed about which games were difficult. We built a third model to investigate whether the frontoparietal activation correlates with how hard a dominance-solvable game is and whether the activation in insula and ACC correlates with how easy a coordination game is. Here, the two main conditions were parametrically modulated by each participant's probability of obtaining a reward in each game (SOM, S2.2 and S5.2). We found a negative correlation between the activation of the precuneus and the participant's probability of obtaining a reward in dominance-solvable games ( Fig. 4C and table S12), which suggests that dominance-solvable games that yielded lower payoffs presented harder mental challenges. In a previous study on working memory, precuneus activity positively correlated with response times, a measure of mental effort (24). Both findings are consistent with the interpretation that subjective measures reflecting harder tasks (higher efforts) correlate with activation in precuneus. A positive correlation between insula activation and the participant's probability of obtaining a reward again suggests that coordination games with a highly salient feature strongly activated the "gut feeling" reported by many participants (Fig. 4D and table S13). A previous study found that the subjective rating of "chills intensity" in music correlates with activation of insula (42). Both findings are consistent with the interpretation that the subjective intensity of how salient a stimulus is correlates with activation in insula.As mentioned, choices were made significantly faster in coordination games than in dominancesolvable games. The results of the second and third models provide additional support for the idea that intuitive and deliberative mental processes have quite different properties. The "slow and effortful" process was more heavily taxed when the dominance-solvable games were harder. The "fast and effortless" process was more strongly activated when coordination was easy.

The Bovine HapMap Consortium* The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.T he emergence of modern civilization was accompanied by adaptation, assimilation, and interbreeding of captive animals. In cattle (Bos taurus), this resulted in the development of individual breeds differing in, for example, milk yield, meat quality, draft ability, and tolerance or resistance to disease and pests. However, despite mapping and diversity studies (1-5) and the identification of mutations affecting some quantitative phenotypes (6-8), the detailed genetic structure and history of cattle are not known.Cattle occur as two major geographic types, the taurine (humpless-European, African, and Asian) and indicine (humped-South Asian, and East African), which diverged >250 thousand years ago (Kya) (3). We sampled individuals representing 14 taurine (n = 376), three indicine (n = 73) (table S1), and two hybrid breeds (n = 48), as well as two individuals each of Bubalus quarlesi and Bubalus bubalis, which diverged from Bos taurus~1.25 to 2.0 Mya (9, 10). All breeds except Red Angus (n = 12) were represented by at least 24 individuals. We preferred individuals that were unrelated for ≥4 generations; however, each breed had one or two sire, dam, and progeny trios to allow assessment of genotype quality.Single-nucleotide polymorphisms (SNPs) that were polymorphic in many populations were primarily derived by comparing whole-genome sequence reads representing five taurine and one indicine breed to the reference genome assembly obtained from a Hereford cow (10) (table S2). This led to the ascertainment of SNPs with high minor allele frequencies (MAFs) within the discovery breeds (table S5). Thus, as expected, with trio progeny removed, SNPs discovered within the taurine breeds had higher average MAFs

Background: Bovine whole genome linkage disequilibrium maps were constructed for eight breeds of cattle. These data provide fundamental information concerning bovine genome organization which will allow the design of studies to associate genetic variation with economically important traits and also provides background information concerning the extent of long range linkage disequilibrium in cattle.

Background: The Bovine HapMap Consortium has generated assay panels to genotype ~30,000 single nucleotide polymorphisms (SNPs) from 501 animals sampled from 19 worldwide taurine and indicine breeds, plus two outgroup species (Anoa and Water Buffalo). Within the larger set of SNPs we targeted 101 high density regions spanning up to 7.6 Mb with an average density of approximately one SNP per 4 kb, and characterized the linkage disequilibrium (LD) and haplotype block structure within individual breeds and groups of breeds in relation to their geographic origin and use.

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Gene mapping and discovery programs have resulted in the detection of numerous DNA "˜markers' for various beef cattle production traits. Prior to commercializing genetic markers, it is important to validate their purported effects on the traits of interest in different breeds and environments, and assess them for correlated responses in associated traits. One of the biggest challenges in achieving this objective is the availability of cattle populations with sufficient phenotypic data to assess the association between various traits and newly discovered genetic markers. Results from such validation studies to date have not been widely published and genetic marker tests sometimes may be commercialized prior to the collection of field validation data. In addition, conflicting reports about some commercially available markers, as well as the recognized occurrence of well-proven bulls with a high EPD for a given trait but carrying two copies of the "wrong"? (unfavorable) marker for that trait, have made some producers wary of investing in DNA-based testing. Producers want to know whether DNA-based tests perform in accordance with the claims of the marketing company and are interested in third-party, independent validation of these tests. The objective of this study was to validate three commercially-available genetic tests (GeneSTAR Quality Grade8, GeneSTAR Tenderness8, and Igenity TenderGENE9).

Background: Analyses of population structure and breed diversity have provided insight into the origin and evolution of cattle. Previously, these studies have used a low density of microsatellite markers, however, with the large number of single nucleotide polymorphism markers that are now available, it is possible to perform genome wide population genetic analyses in cattle. In this study, we used a high-density panel of SNP markers to examine population structure and diversity among eight cattle breeds sampled from Bos indicus and Bos taurus.

Toll-like receptor 4 (TLR4) is a cell-surface receptor that activates innate and adaptive immune responses. Because it recognizes a broad class of pathogen-associated molecular patterns presented by lipopolysaccharides and lipoteichoic acid, TLR4 is a candidate gene for resistance to a large number of diseases. In particular, mouse models suggest TLR4 as a candidate gene for resistance to major agents in bovine respiratory disease and Johne's disease. The coding sequence of bovine TLR4 is divided into three exons, with intron͞exon boundaries and intron sizes similar to those of human TLR4 transcript variant 1. We amplified each exon in 40 individuals from 11 breeds and screened the sequence for singlenucleotide polymorphisms (SNPs). We identified 32 SNPs, 28 of which are in the coding sequence, for an average of one SNP per 90 bp of coding sequence. Eight SNPs were nonsynonymous and potentially alter specificity of pathogen recognition or efficiency of signaling. To evaluate the functional importance of these SNPs, we used codon-substitution models to detect diversifying selection in an extracellular region that may physically interact with ligands. One nonsynonymous SNP is located within this region, and other substitutions are in adjacent regions that may interact with coreceptor molecules. The 32 SNPs were found in 20 haplotypes that can be assigned to geographic ranges of origin. Haplotype-tagging SNP analysis indicated that 12 SNPs need to be genotyped to distinguish these 20 haplotypes. These data provide a basic understanding of bovine TLR4 sequence variation and supply haplotype markers for disease association studies.