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Background: Major advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies., Results: We present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250× more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use., Conclusions: We demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species., (© The Author(s) 2020. Published by Oxford University Press.)

Embryonic stem cells (ESCs) are derived from the inner cell mass of preimplantation blastocysts. For decades, attempts to efficiently derive ESCs in animal livestock species have been unsuccessful, but this goal has recently been achieved in cattle. Together with the recent reconstitution of the germ cell differentiation processes from ESCs in mice, these achievements open new avenues for the development of promising technologies oriented toward improving health, animal production, and the environment. In this article, we present a strategy that will notably accelerate genetic improvement in livestock populations by reducing the generational interval, namely in vitro breeding (IVB). IVB combines genomic selection, a widely used strategy for genetically improving livestock, with ESC derivation and in vitro differentiation of germ cells from pluripotent stem cells. We also review the most recent findings in the fields on which IVB is based. Evidence suggests this strategy will be soon within reach., (© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Parameters of bone geometry such as width, length, and cross-sectional area are major determinants of bone strength. Although these traits are highly heritable, few genes influencing bone geometry have been identified. Here, we dissect a major quantitative trait locus (QTL) influencing femur size. This QTL was originally identified in an F2 cross between the C57BL/6J-hg/hg (HG) and CAST/EiJ strains and was referred to as femur length in high growth mice 2 ( Feml2 ). Feml2 was located on chromosome (Chr.) 9 at ∼20 cM. Here, we show that the HG.CAST-( D9Mit249-D9Mit133 )/Ucd congenic strain captures Feml2 In an F2 congenic cross, we fine-mapped the location of Feml2 to an ∼6 Mbp region extending from 57.3 to 63.3 Mbp on Chr. 9. We have identified candidates by mining the complete genome sequence of CAST/EiJ and through allele-specific expression (ASE) analysis of growth plates in C57BL/6J × CAST/EiJ F1 hybrids. Interestingly, we also find that the refined location of Feml2 overlaps a cluster of six independent genome-wide associations for human height. This work provides the foundation for the identification of novel genes affecting bone geometry., (Copyright © 2017 Sabik et al.)

Epizootic bovine abortion (EBA), or "foothill abortion," is the leading cause of beef cattle abortion in California and has also been reported in Nevada and Oregon. In the 1970s, the soft-shelled tick Ornithodoros coriaceus , or "pajaroello tick," was confirmed as the disease-transmitting vector. In 2005, a novel Deltaproteobacterium was discovered as the etiologic agent of EBA (aoEBA), recently named Pajaroellobacter abortibovis This organism cannot be grown in culture using traditional microbiological techniques; it can only be grown in experimentally-infected severe combined immunodeficient (SCID) mice. The objectives of this study were to perform a de novo genome assembly for P. abortibovis and identify and validate potential antigenic proteins as candidates for future recombinant vaccine development. DNA and RNA were extracted from spleen tissue collected from experimentally-infected SCID mice following exposure to P. abortibovis This combination of mouse and bacterial DNA was sequenced and aligned to the mouse genome. Mouse sequences were subtracted from the sequence pool and the remaining sequences were de novo assembled at 50x coverage into a 1.82 Mbp complete closed circular Deltaproteobacterial genome containing 2250 putative protein-coding sequences. Phylogenetic analysis of P. abortibovis predicts that this bacterium is most closely related to the organisms of the order Myxococcales, referred to as Myxobacteria. In silico prediction of vaccine candidates was performed using a reverse vaccinology approach resulting in the identification and ranking of the top 10 candidate proteins that are likely to be antigenic. Immunologic testing of these candidate proteins confirmed antigenicity of seven of the nine expressed protein candidates using serum from P. abortibovis immunized mice., (Copyright © 2017 Welly et al.)

Transmission ratio distortion (TRD) is the departure from the expected genotypic frequencies under Mendelian inheritance. This departure can be due to multiple physiological mechanisms during gametogenesis, fertilization, fetal and embryonic development, and early neonatal life. Although a few TRD loci have been reported in mouse, inheritance patterns have never been evaluated for TRD. In this article, we developed a Bayesian binomial model accounting for additive and dominant deviation TRD mechanisms. Moreover, this model was used to perform genome-wide scans for TRD quantitative trait loci (QTL) on six F2 mouse crosses involving between 296 and 541 mice and between 72 and 1854 genetic markers. Statistical significance of each model was checked at each genetic marker with Bayes factors. Genome scans revealed overdominance TRD QTL located in mouse chromosomes 1, 2, 12, 13, and 14 and additive TRD QTL in mouse chromosomes 2, 3, and 15, although these results did not replicate across mouse crosses. This research contributes new statistical tools for the analysis of specific genetic patterns involved in TRD in F2 populations, our results suggesting a relevant incidence of TRD phenomena in mouse with important implications for both statistical analyses and biological research.

Great interest was aroused by reports, based on microsatellite markers, of high levels of statistically significant long-range and nonsyntenic linkage disequilibrium (LD) in livestock. Simulation studies showed that this could result from population family structure. In contrast, recent SNP-based studies of livestock populations report much lower levels of LD. In this study we show, on the basis of microsatellite data from four cattle populations, that high levels of long-range LD are indeed obtained when using the multi-allelic D' measure of LD. Long-range and nonsyntenic LD are exceedingly low, however, when evaluated by the standardized chi-square measure of LD, which stands in relation to the predictive ability of LD. Furthermore, specially constructed study populations provided no evidence for appreciable LD resulting from family structure at the grandparent level. We propose that the high statistical significance and family structure effects observed in the earlier studies are due to the use of large sample sizes, which accord high statistical significance to even slight deviations from asymptotic expectations under the null hypothesis. Nevertheless, even after taking sample size into account, our results indicate that microsatellites testify to the presence of usable LD at considerably wider separation distances than SNPs, suggesting that use of SNP haplotypes may considerably increase the usefulness of a given fixed SNP array.

The mutational input of genetic variance per generation (sigma(m)(2)) is the lower limit of the genetic variability in inbred strains of mice, although greater values could be expected due to the accumulation of new mutations in successive generations. A mixed-model analysis using Bayesian methods was applied to estimate sigma(m)(2) and the across-generation accumulated genetic variability on litter size in 46 generations of a C57BL/6J inbred strain. This allowed for a separate inference on sigma(m)(2) and on the additive genetic variance in the base population (sigma(a)(2)). The additive genetic variance in the base generation was 0.151 and quickly decreased to almost null estimates in generation 10. On the other hand, sigma(m)(2) was moderate (0.035) and the within-generation mutational variance increased up to generation 14, then oscillating between 0.102 and 0.234 in remaining generations. This pattern suggested the existence of a continuous uploading of genetic variability for litter size (h(2)=0.045). Relevant genetic drift was not detected in this population. In conclusion, our approach allowed for separate estimation of sigma(a)(2) and sigma(m)(2) within the mixed-model framework, and the heritability obtained highlighted the significant and continuous influence of new genetic variability affecting the genetic stability of inbred strains.

Previous speed congenic analysis has suggested that the expression of growth and obesity quantitative trait loci (QTL) on distal mouse chromosomes (MMU) 2 and 11, segregating between the CAST/EiJ (CAST) and C57BL/6J-hg/hg (HG) strains, is dependent on sex. To confirm, fine map, and further evaluate QTL x sex interactions, we constructed congenic by recipient F2 crosses for the HG.CAST-(D2Mit329-D2Mit457)N(6) (HG2D) and HG.CAST-(D11Mit260-D11Mit255)N(6) (HG11) congenic strains. Over 700 F2 mice were densely genotyped and phenotyped for a panel of 40 body and organ weight, skeletal length, and obesity-related traits at 9 weeks of age. Linkage analysis revealed 20 QTL affecting a representative subset of phenotypes in HG2DF2 and HG11F2 mice. The effect of sex was quantified by comparing two linear models: the first model included sex as an additive covariate and the second incorporated sex as an additive and an interactive covariate. Of the 20 QTL, 8 were sex biased, sex specific, or sex antagonistic. Most traits were regulated by single QTL; however, two closely linked loci were identified for five traits in HG2DF2 mice. Additionally, the confidence intervals for most QTL were significantly reduced relative to the original mapping results, setting the stage for quantitative trait gene (QTG) discovery. These results highlight the importance of assessing the contribution of sex in complex trait analyses.

The high growth (hg) mutation increases body size in mice by 30-50%. Given the complexity of the genetic regulation of animal growth, it is likely that the effect of this major locus is mediated by other quantitative trait loci (QTL) with smaller effects within a web of gene interactions. In this article, we extend our functional mapping model to characterize modifier QTL that interact with the hg locus during ontogenetic growth. Our model is derived within the maximum-likelihood context, incorporated by mathematical aspects of growth laws and implemented with the EM algorithm. In an F2 population founded by a congenic high growth (HG) line and non-HG line, a highly additive effect due to the hg gene was detected on growth trajectories. Three QTL located on chromosomes 2 and X were identified to trigger significant additive and/or dominant effects on the process of growth. The most significant finding made from our model is that these QTL interact with the hg locus to affect the shapes of the growth process. Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals.

Various genes related to early events in human gustation have recently been discovered, yet a thorough understanding of taste transduction is hampered by gaps in our knowledge of the signaling chain. As a first step toward gaining additional insight, the expression specificity of genes in human taste tissue needs to be determined. To this end, a fungiform papillae cDNA library has been generated and analyzed. For validation of the library, taste-related gene probes were used to detect known molecules. Subsequently, DNA sequence analysis was performed to identify further candidates. Of 987 clones sequenced, clustering results in 288 contigs. Comparison of these contigs with genomic databases reveals that 207 contigs (71.9%) match known genes, 16 (5.6%) match hypothetical genes, eight (2.8%) match repetitive sequences and 57 (19.8%) have no or low similarity to annotated genes. The results indicate that despite a high level of redundancy, this human fungiform cDNA library contains specific taste markers and is valuable for investigation of both known and novel taste-related genes.

Animals with extreme body growth frequently experience poor reproductive performance, but the cause for this association has not been clearly established. A line of mice homozygous for the high growth (hg) mutation, a mutation that has a major effect on post-weaning growth, exhibits several reproductive deficits including an abnormally high incidence of luteal failure. The objective of the present study was to investigate luteal failure in high-growth (HG) mice during pregnancy and to determine whether the cause of the apparent luteal failure resides in the ovary or the hypothalamic-pituitary unit. In HG females with a demonstrated history of infertility, progesterone injections (1 mg s.c. daily) beginning on Day 1 postcoitum (p.c.) increased the proportion of animals pregnant at Day 17 of gestation. Twice-daily injections of 100 microgram of ovine prolactin (PRL) in alkaline saline given to another group of females beginning on Day 1 p.c. increased the proportion of HG females that were pregnant on Day 6 of gestation compared with saline-injected HG females, although PRL did not increase the pregnancy rate in HG females when compared with a group of noninjected control females. When ovaries from HG females were transplanted into ovariectomized congenic C57 hosts, the C57 graft hosts displayed normal estrous cycles, and upon mating the majority of graft hosts became pregnant. In contrast, when ovaries from C57 females were transplanted into ovariectomized HG hosts, the HG graft hosts displayed normal estrous cycles, but upon mating most were unable to maintain pregnancy. These results suggest that the hypothalamic-pituitary unit of the HG female provides an inadequate signal to the ovaries to maintain pregnancy. Luteal failure in HG females may be due to insufficient PRL as required for establishment and early maintenance of the CL during pregnancy in mice.

The high growth locus (hg) causes a major increase in weight gain and body size in mice. As a first step to map-based cloning of hg, we developed a genetic map of the hg-containing region using interval mapping of 403 F2 from a C57BL/6J-hghg x CAST/EiJ cross. The maximum likelihood position of hg was at the chromosome 10 marker D10Mit41 (LOD = 24.8) in the F2 females and 1.5 cM distal to D10Mit41 (LOD = 9.56) in the F2 males with corresponding LOD 2 support intervals of 3.7 and 5.4 cM, respectively. The peak LOD scores were significantly higher than the estimated empirical threshold LOD values. The localization of hg by interval mapping was supported by a test cross of F2 mice recombinant between the LOD 2 support interval and the flanking marker. The interval mapping and test-cross results indicate that hg is not allelic with candidate genes Igf1 or decorin (Dcn), a gene that was mapped close to hg in this study. The hg inheritance was recessive in females, although we could not reject recessive or additive inheritance in males. Possible causes for sex differences in peak LOD scores and for the distortion of transmission ratios observed in F2 males are discussed. The genetic map of the hg region will facilitate further fine mapping and cloning of hg, and allow searches for a homologous quantitative trait locus affecting growth in humans and domestic animals.

Growth rate, body composition, cell number, cell size, and the activity of four dehydrogenase enzymes were studied from 10 to 25 days of age in one control (1C) and three lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for large 21-day pupae weight.-Selected lines were two- to three-fold larger in size than the control line throughout development. No major differences in percent of protein were detected among the lines but at any particular age, the selected lines were found to have a higher fat content than the control line. The differences in fat content were closely correlated with development such that all the lines reached very similar levels of percent of fat just prior to pupation. Water content showed an inverse relation to percent of fat.-Selection was observed to have caused major changes in the cellular response to growth. The selected lines had an average of from 17% to 48% larger cells (measured as protein/DNA) and were found to have from 37 to 62% more cells (measured as total DNA) than the control line at all ages from 10 to 19 days of age. In addition, the selected lines had a higher RNA content at all ages studied and higher RNA:DNA ratios at the young ages. In contrast the enzyme activities of ICDH and LDH were 60% lower. The results are interpreted as indicating that a more efficient metabolic machinery had evolved in the rapidly growing selected lines.

Food consumption, feed efficiency, metabolic rate and glucose utilization were studied throughout development in one control (1C) and three selected lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for 21-day pupae weight. Growth rate, body composition, cellular growth and the activity of four dehydrogenase enzymes in the same lines have been reported (Medrano and Gall 1976).-Larva of selected lines consumed 1.2 times as much food as the control and gained an average of 2.9 times as much weight. The rapid growth of the selected lines was associated with a gross feed efficiency 20 to 30% above that for the control line. There was also a small but consistent improvement in the conversion of digested food. Average digestibility was higher for selected lines.-There was little apparent differentiation between the control and selected lines in metabolic rate/individual, but the rate measured on a per-unit weight basis was two- to three-fold greater for the control during the active growth stages. Respiratory quotients (R.Q.) of 1.0, indicative of carbohydrate oxidation, were observed through larval growth in all lines. Pupae at 21 days showed R.Q. values greater than 1.0, which were interpreted as resulting from a phenomenon in insects in which CO(2) is released by pupae, in large bursts at irregular intervals. The rate constant of glucose oxidation, measured as the rate of C(14) labelled CO(2) respired during 2- to 6-hour incubation periods, was two- to three-fold higher in the control. In addition, the control line larvae expired 5% to 17% more of the ingested C(14) as CO(2). It was apparent that control line individuals maintained a much more active turnover of metabolites but without an effective retention of carbon as body substances. The results are discussed in support of the hypothesis that selection for large body size resulted in improved control mechanisms that influence the biological efficiency of growth in Tribolium.