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BackgroundHumplessBos tauruscattle are one of the earliest domestic cattle in Africa, followed by the arrival of humpedBos indicuscattle. The diverse indigenous cattle breeds of Africa are derived from these migrations, with most appearing to be hybrids betweenBos taurusandBos indicus. The present study examines the patterns of admixture, diversity, and relationships among African cattle breeds.MethodsData for ~ 40 k SNPs was obtained from previous projects for 4089 animals representing 35 African indigenous, 6 EuropeanBos taurus, 4Bos indicus,and 5 African crossbred cattle populations. Genetic diversity and population structure were assessed using principal component analyses (PCA), admixture analyses, and Wright’sFstatistic. The linkage disequilibrium and effective population size (Ne) were estimated for the pure cattle populations.ResultsThe first two principal components differentiatedBos indicusfrom EuropeanBos taurus, and AfricanBos taurusfrom other breeds. PCA and admixture analyses showed that, except for recently admixed cattle, all indigenous breeds are either pure AfricanBos taurusor admixtures of AfricanBos taurusandBos indicus.The African zebu breeds had highest proportions ofBos indicusancestry ranging from 70 to 90% or 60 to 75%, depending on the admixture model. Other indigenous breeds that were not 100% AfricanBos taurus, ranged from 42 to 70% or 23 to 61%Bos indicusancestry. The AfricanBos tauruspopulations showed substantial genetic diversity, and other indigenous breeds show evidence of having more than one African taurine ancestor.Neestimates based onr2andr2adjshowed a decline inNefrom a large population at 2000 generations ago, which is surprising for the indigenous breeds given the expected increase in cattle populations over that period and the lack of structured breeding programs.ConclusionAfrican indigenous cattle breeds have a large genetic diversity and are either pure AfricanBos taurusor admixtures of AfricanBos taurusandBos indicus.This provides a rich resource of potentially valuable genetic variation, particularly for adaptation traits, and to support conservation programs. It also provides challenges for the development of genomic assays and tools for use in African populations.

Background Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. Case presentation A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child’s passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. Conclusion The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

Understanding the genetic structure of adaptation and productivity in challenging environments is necessary for designing breeding programs that suit such conditions. Crossbred dairy cattle in East Africa resulting from over 60 years of crossing exotic dairy breeds with indigenous cattle plus inter se matings form a highly variable admixed population. This population has been subject to natural selection in response to environmental stresses, such as harsh climate, low-quality feeds, poor management, and strong disease challenge. Here, we combine two complementary sets of analyses, genome-wide association (GWA) and signatures of selection (SoS), to identify genomic regions that contribute to variation in milk yield and/or contribute to adaptation in admixed dairy cattle of Kenya. Our GWA separates SNP effects due to ancestral origin of alleles from effects due to within-population linkage disequilibrium. The results indicate that many genomic regions contributed to the high milk production potential of modern dairy breeds with no region having an exceptional effect. For SoS, we used two haplotype-based tests to compare haplotype length variation within admixed and between admixed and East African Shorthorn Zebu cattle populations. The integrated haplotype score (iHS) analysis identified 16 candidate regions for positive selection in the admixed cattle while the between population Rsb test detected 24 divergently selected regions in the admixed cattle compared to East African Shorthorn Zebu. We compare the results from GWA and SoS in an attempt to validate the most significant SoS results. Only four candidate regions for SoS intersect with GWA regions using a low stringency test. The identified SoS candidate regions harbored genes in several enriched annotation clusters and overlapped with previously found QTLs and associations for different traits in cattle. If validated, the GWA and SoS results indicate potential for SNP-based genomic selection for genetic improvement of smallholder crossbred cattle.

To understand farmers’ preference and perceptions of breed attributes, breeding and feeding practices, 419 households in western Kenya were interviewed in a cross-sectional survey. Respondents scored their preference for cattle breeds, traits and breeding methods on a scale of 1 (most preferred) to 5 (least preferred). Preferences were compared using multinomial logistic regression models on weighted scores. The Ayrshire breed was most preferred followed by the Friesian. Using hardship tolerance as a reference trait, the Friesian was preferred 4.86 times more for high milk production and Ayrshire, Jersey and Guernsey breeds 4.61, 4.60 and 4.18 times (p 68%) of respondents used natural mating, because it was readily available and cheaper. The current study highlights the importance of taking into account farmers’ objectives and the production environment when designing breed improvement programmes and recommends packaging of breeding together with feeding interventions.

African livestock breeds are numerous and diverse, and typically well adapted to the harsh environment conditions under which they perform. They have been used over centuries to provide livelihoods as well as food and nutritional security. However, African livestock systems are dynamic, with many small- and medium-scale systems transforming, to varying degrees, to become more profitable. In these systems the women and men livestock keepers are often seeking new livestock breeds or genotypes - typically those that increase household income through having enhanced productivity in comparison to traditional breeds while maintaining adaptedness. In recent years genomic approaches have started to be utilized in the identification and development of such breeds, and in this article we describe a number of examples to this end from sub-Saharan Africa. These comprise case studies on: (a) dairy cattle in Kenya and Senegal, as well as sheep in Ethiopia, where genomic approaches aided the identification of the most appropriate breed-type for the local productions systems; (b) a cross-breeding program for dairy cattle in East Africa incorporating genomic selection as well as other applications of genomics; (c) ongoing work toward creating a new cattle breed for East Africa that is both productive and resistant to trypanosomiasis; and (d) the use of African cattle as resource populations to identify genomic variants of economic or ecological significance, including a specific case where the discovery data was from a community based breeding program for small ruminants in Ethiopia. Lessons learnt from the various case studies are highlighted, and the concluding section of the paper gives recommendations for African livestock systems to increasingly capitalize on genomic technologies.

The ability to generate transgenic animals has existed for over 30 years, and from those early days many predicted that the technology would have beneficial applications in agriculture. Numerous transgenic agricultural animals now exist, however to date only one product from a transgenic animal has been approved for the food chain, due in part to cumbersome regulations. Recently, new techniques such as precision breeding have emerged, which enables the introduction of desired traits without the use of transgenes. The rapidly growing human population, environmental degradation, and concerns related to zoonotic and pandemic diseases have increased pressure on the animal agriculture sector to provide a safe, secure and sustainable food supply. There is a clear need to adopt transgenic technologies as well as new methods such as gene editing and precision breeding to meet these challenges and the rising demand for animal products. To achieve this goal, cooperation, education, and communication between multiple stakeholders-including scientists, industry, farmers, governments, trade organizations, NGOs and the public-is necessary. This report is the culmination of concepts first discussed at an OECD sponsored conference and aims to identify the main barriers to the adoption of animal biotechnology, tactics for navigating those barriers, strategies to improve public perception and trust, as well as industry engagement, and actions for governments and trade organizations including the OECD to harmonize regulations and trade agreements. Specifically, the report focuses on animal biotechnologies that are intended to improve breeding and genetics and currently are not routinely used in commercial animal agriculture. We put forward recommendations on how scientists, regulators, and trade organizations can work together to ensure that the potential benefits of animal biotechnology can be realized to meet the future needs of agriculture to feed the world.

SummaryAnimal breeding for increased productivity over the past 50 to 60 years has been very successful in terms of increasing growth rate, milk yield and egg production in most livestock producing regions of the world (Rauwet al., 1998). However, this success has not registered that well in most countries in sub-Saharan Africa (SSA). Ironically, just like most developing regions, SSA is faced with the challenge to increase rapidly the agricultural productivity to help feed their growing human populations without depleting the natural resource base (Rege, 2005). Genetic improvement of livestock depends on access to genetic variation and effective methods for exploiting this variation (Rege, 2005). This is where human capacity and infrastructure for decision-support systems in animal breeding are required. This paper provides a synthesis of views from a cross-section of livestock production experts working in SSA. These views were collated through an e-conference which was held from 8th March to 20th April 2011. The e-conference discussed future research and development (R&D) needs for animal breeding and genetics in SSA and how they can be met. The e-conference attracted 43 participants from 17 countries. Results from the e-conference demonstrated that the R&D institutions and infrastructure in SSA vary widely in terms of both the physical and human capacity. Equally varied is the level of utilization of these institutions. In terms of training in Animal Breeding and Genetics, although most universities/colleges have programmes in Animal Science and teach animal breeding and genetics, there are very few practicing animal breeders. Lack of mentorship programmes and collaboration, and in some cases lack of appropriate jobs, continue to contribute to this ‘leaking pipeline’ phenomenon. The following is a summary of the consensus stemming from the conference on how the efficiency and effectiveness of livestock genetic improvement in SSA could be enhanced. First, the need to augment the approach that promotes animal breeding and genetics as part of a wider agriculture and rural development system, second, collaboration both within Africa and with those in the Diaspora should be further tapped into and utilized as a source of capacity for R&D and third, initiative of sharing resources and research platforms such as pooling data for genetic analysis from across institutions, and even across countries, should be encouraged in case where this is advantageous to do so.

International audience; BackgroundPerformance recording and genotyping in the multiplier tier of multi-tiered sheep breeding schemes could potentially reduce the difference in the average genetic merit between nucleus and commercial flocks, and create additional economic benefits for the breeding structure.MethodsThe genetic change in a multiple-trait breeding objective was predicted for various selection strategies that included performance recording, parentage testing and genomic selection. A deterministic simulation model was used to predict selection differentials and the flow of genetic superiority through the different tiers. Cumulative discounted economic benefits were calculated based on trait gains achieved in each of the tiers and considering the extra revenue and associated costs of applying recording, genotyping and selection practices in the multiplier tier of the breeding scheme.ResultsPerformance recording combined with genomic or parentage information in the multiplier tier reduced the genetic lag between the nucleus and commercial flock by 2 to 3 years. The overall economic benefits of improved performance in the commercial tier offset the costs of recording the multiplier. However, it took more than 18 years before the cumulative net present value of benefits offset the costs at current test prices. Strategies in which recorded multiplier ewes were selected as replacements for the nucleus flock did modestly increase profitability when compared to a closed nucleus structure. Applying genomic selection is the most beneficial strategy if testing costs can be reduced or by genotyping only a proportion of the selection candidates. When the cost of genotyping was reduced, scenarios that combine performance recording with genomic selection were more profitable and reached breakeven point about 10 years earlier.ConclusionsEconomic benefits can be generated in multiplier flocks by implementing performance recording in conjunction with either DNA pedigree recording or genomic technology. These recording practices reduce the long genetic lag between the nucleus and commercial flocks in multi-tiered breeding programs. Under current genotyping costs, the time to breakeven was found to be generally very long, although this varied between strategies. Strategies using either genomic selection or DNA pedigree verification were found to be economically viable provided the price paid for the tests is lower than current prices, in the long-term.

Background BK virus (BKV)-associated nephropathy (BKVAN) is often associated with renal graft dysfunction. When renal transplant recipients present with high clinical suspicion for BKVAN (high serum and urine BKV titer with graft dysfunction) but their graft biopsies stain negatively for BKV, non-correlated situations between the two tests often lead to a dilemma about how to treat them. Methods This retrospective investigation was conducted to determine how real-time quantitative PCR (qPCR) for BKV, routinely applied to serum and urine, could be helpful in identifying the existing BKV in biopsy tissue stained negatively for BKV. Results DNA was extracted from each specimen through the use of five 10-μm curls from the tissue block with use of the QIAamp DNA FFPE Tissue Kit (Qiagen), followed by BKV qPCR to determine copies of BKV/μg of biopsy tissue DNA. Group 1 (11 negative renal controls for BKV) demonstrated 0 to 9 BKV copies/μg DNA. Except for 3 focally staining cases showing low BKV, the remaining 10 positive renal controls in group 2 (13 positive transplant biopsies staining positively) demonstrated elevated BKV up to 160 million copies/μg DNA. Group 3 transplants (13 uncertain transplants with negative BKV staining but positive liquid BKV) were negative for BKV (0–12 copies/μg) in 4 of 13, had low BKV copies (36–346 copies/μg) in 5 of 13, and had high BKV copies (17,240–526,945 copies/μg) in 4 of 13 cases, through the use of qPCR. Conclusions The data indicate that qPCR from paraffin-embedded tissue as a backup test is sensitive for ruling in/out BKV infection in renal transplant biopsies, particularly in uncertain cases.

Body linear measurements, and specifically heart girth (HG), have been shown to be useful predictors of cattle liveweight. To test the accuracy of body linear measurements for predicting liveweight, crossbred dairy cattle of different genotypes were measured and weighed. A total of 352 mature cows and 100 heifers were weighed using an electronic weighing scale and measurements of HG, body length, height at withers were taken using an ordinary measuring tape and body condition scored (BCS) using a five-point scale. The animals were grouped according to genotype and age. Genotype classification was undertaken from farmer recall and by visual appraisal as 40-60, 61-80 or 81-100 % exotic (non-indigenous). Age classification was simply as mature cows or heifers. Liveweight of the animals ranged from 102 to 433 kg. Liveweight was strongly correlated with HG (r = 0.84) and body condition scores (r = 0.70) and moderately correlated with body length (r = 0.64) and height at withers (0.61). Regressing LW on HG measurements gave statistically significant (P 0.01) equations with R(2) ranging from of 0.53 to 0.78 and residual standard deviation ranging from 18.11 to 40.50 kg. The overall model developed (adjusted R(2) = 0.71) had a prediction error of 26 kg (or 11 % of the mean) and predicted LW of over 95 % of crossbred dairy cattle in the range of 100-450 kg, regardless of age and breed group. Including BCS in the model slightly improved the model fit but not the prediction error. It was concluded that the model can be useful in making general management decisions in smallholder farms.

Summary Microsatellite markers are commonly used for population genetic analyses of livestock. However, up to now, combinations of microsatellite data sets or comparison of population genetic parameters from different studies and breeds has proven difficult. Often different genotyping methods have been employed, preventing standardization of microsatellite allele calling. In other cases different sets of markers have been genotyped, providing differing estimates of population genetic parameters. Here, we address these issues and illustrate a general two-step regression approach in cattle using three different sets of microsatellite data, to combine population genetics estimates of diversity and admixture. This regression-based method is independent of the loci genotyped but requires common breeds in the data sets. We show that combining microsatellite data sets can provide new insights on the origin and geographical distribution of genetic diversity and admixture in cattle, which will facilitate global management of this livestock species.

Summary The improvement and utilisation of host genetic resistance to disease is an attractive option as a component of livestock disease control in a wide range of situations. This paper reviews the situations where genetic resistance of the host is likely to be a useful component of disease control and provides a framework for deciding whether genetic improvement of resistance is likely to be worthwhile. Discussion is focused on low-input production systems in the developing world, where disease resistance is particularly important. The authors propose an integrated strategy for the use of molecular markers in assessing genetic diversity and in utilising and improving host genetic resistance to disease. The integrated approach assures that there is value in the molecular genetic information whether or not it proves useful in genetic selection, a feature that should prove attractive to funding and executing agencies.

The world's domestic animal breeds represent an important resource for economic development and livelihood security. Extensive genetic diversity in these breeds allows the existence of livestock in all but the most extreme environments globally, providing a range of products and functions. Unfortunately, a large number of breeds have been lost and many more are at risk of loss. An important research and development goal is the systematic evaluation of breeds in production systems where they arc typically found, quantitative assessment of the genetic diversity they possess, the definition of relationships amongst breeds and the implementation of programmes for their effective management, including development of policies and strategies for conservation and sustainable utilisation. The key issues of threats to livestock genetic resources, justification for conservation, conservation strategies, priority-setting for conservation are summarised. The potential contribution of economic valuation in ensuring equitable sharing of benefits derived from domestic animal genetic resources (AnGR) is also discussed. Decisions will be required about which breeds are of highest priority, and which conservation or management options represent optimal use of resources for diversity conservation. There is urgent need for the development and application of economic and policy analysis tools to aid rational decision-making in the management of the global domestic AnGR.

About 30% of all farm animal breeds worldwide are at risk of extinction. To prevent this irreversible erosion of genetic diversity, the limited funds available for conservation need to be allocated in the most efficient way. Applying the diversity concept of Weitzman [Quart. J. Econ. CVII (1992) 363; Quart. J. Econ. CVIII (1993) 157] this paper presents a framework for the allocation of a given budget among a set of breeds such that the expected amount of between-breed diversity conserved is maximized. As a novel methodological contribution, a functional relationship between conservation funds spent in one population and the conservation effect in terms of reduced extinction probability is suggested. Based on arguments from population genetics, three different functions are derived, which may reflect the range of possible functions in typical conservation situations. The methodology is illustrated with an example of 23 African zebu and zenga cattle breeds. The results indicate that conservation funds should be spent on only three to nine of the 23 breeds, depending on the model used. Highest priority is given to breeds, for which the ‘conservation potential’, that is, the product of extinction probability and marginal diversity is maximum, and these are not necessarily the most endangered breeds. The methodology can be extended to the maximization of total utility, which incorporates diversity, as well as other direct use, and special value, characteristics. However, a number of essential input parameters such as extinction probabilities and economic values are lacking and realistic models for developing cost-efficient conservation strategies have to be derived. Given these lacking bits of information become available, the methodology suggested provides a breakthrough towards applicability of diversity-based approaches for decision taking in conservation programs. # 2003 Elsevier Science B.V. All rights reserved.

Reliability of parentage test panels is usually based on its power to exclude wrong parentage assignments based on allele frequencies. We evaluated the rates of false exclusions and inclusions in parentage assignments, and how these results are affected by allele frequencies, panel sizes and the number of allowed mismatches. We also evaluated the reliability of parentage testing by comparing populations with distinct genetic backgrounds using pure and composite families of cattle and sheep. Allowing for 1% genotype mismatches in true parent-offspring relations provided the best compromise between false-positive and false-negative assignments. Pure breeds needed at least 200-210 single-nucleotide polymorphism (SNP) markers to correctly assign relations, but between 700 and 890 markers to avoid assigning incorrect relationships. Composite breeds needed between 220 (sheep) and 500 (cattle) markers for correct assignment; 680 (cattle) to 4400 (sheep) SNPs were needed to eliminate false-positive assignments. Allowing 0% genotype mismatches decreased false-positive but increased false-negative assignments, whilst a higher threshold of 2% showed the opposite effects. Panels with high minor allele frequencies (0.35-0.45) provided the best chance for correct parentage resolutions requiring fewer markers. Further, we propose that a dynamic threshold would allow adapting to population specific error rates. A comparison to the performance of the official International Society for Animal Genetics SNP panel for cattle and a recently published SNP panel for sheep showed that randomly selected markers performed only slightly worse for the applied parentage test based on opposing homozygotes. This suggests that even with carefully selected panels, only marginal assignment improvements are obtainable for a particular number of SNPs. The main point for improvement is the number of markers used. We recommend using at least 200 SNP markers for parentage testing if the aim is to reduce false-negative results. To fully exclude false positives at least 700 markers are required.

The objective of this study was to evaluate whether the efficacy of marker assisted selection (MAS) could be improved by considering a confidence interval (CI) of QTL position. Specifically, MAS was applied for within-family selection in a stochastic simulation of a closed nucleus herd. The location and effect of the QTL were estimated by least squares interval mapping with a granddaughter design and marker information was then used in a top down scheme. Three approaches were used to select the best bull within full sibships of 3 or 40 bulls. All three were based on the probability of inheriting the favorable allele from the grandsire (PROB). The first method selected the sib with the highest PROB at the location with the highest F-ratio (MAX). The other two approaches were based on sums of estimated regression coefficients weighted by PROB at each cM within a 95% CI based on either bootstrapping (BOOT) or approximate LOD scores (LOD). Accounting for CI increased the relative genetic gain in all scenarios. The average breeding value (BV) of the selected bulls was increased by 2.00, 2.60 and 2.59% when MAS was applied using MAX, BOOT and LOD, respectively, compared to random selection (h2=0.30). Selected bulls carried the correct allele in 63.0, 68.5, 67.6 and 50.1% of the cases for MAX, BOOT, LOD and random selection, respectively. Beru;cksichtigung der Unsicherheit von QTL Positionen bei Marker-gestu;tzter Vorselektion von jungen Bullen vor der Nachkommenpru;fung Das Ziel dieser Studie war es zu prufen, ob die Effizienz von MAS (Marker gestutzte Selektion) durch Berucksichtigung des Konfidenzintervalls (CI) einer QTL Position verbessert werden kann. Es wurde MAS bei der Selektion innerhalb Familien in einer geschlossenen Nukleus Herde in einer stochastischen Simulation angewandt. Die Postition und der Effekt des QTL wurden in einem Granddaughter Design mit einer Least=Square Intervall Kartierung geschatzt. Die Marker Informationen wurden dann in einem top-down-Schema verwendet. Drei Ansatze fanden Verwendung, um den besten Bullen innerhalb von Vollgeschwistern von 3 oder 40 Bullen zu selektieren. Alle drei Ansatze basieren auf der Wahrscheinlichkeit, ein zu bevorzugendes Allel vom Grossvater zu erben (PROB). Bei der ersten Methode wurden die Geschwister mit der hochsten PROB an der Position mit dem hochsten F-Wert selektiert (MAX). Die beiden anderen Ansatze basierten auf den Summen der geschatzten Regressionskoeffizienten, gewichtet nach PROB an jedem cM innerhalb eines 95%igen CI, das entweder auf Bootstrapping (BOOT) oder approximativen LOD Scores (LOD) basiert. Die Berucksichtigung des CI vergrosserte den relativen genetischen Fortschritt in allen Szenarien. Bei Anwendung von MAS waren die durchschnittlichen Zuchtwerte der selektierten Bullen bei Verwendung von MAX, BOOT und LOD verglichen mit zufalliger Selektion (h2=0,30) um 2,00, 2,60 und 2,59% gestiegen. Die selektierten Bullen trugen das richtige Allel bei den entsprechenden Berechnungen MAX, BOOT, LOD und zufalliger Selektion in 63,0, 68,5, 67,6 und 50,1% der Falle.

A bioeconomic model of an integrated Canadian beef production system was developed to derive economic values for genetic improvement of multiple traits. The breeding objective was assumed to be profit maximization of the integrated enterprise. Sixteen input traits were identified as potentially influencing returns and costs in the system. These were mature size, direct and maternal calving ease (in heifers and cows separately), cow fertility, calf survival, cow survival, peak milk yield, residual post-weaning growth rate, residual feed intake in growing animals, residual feed intake in mature animals, residual slaughter weight and dressing percentage at constant backfat thickness, marbling and lean percentage. Most traits were defined to be functionally independent of each other. Thus, traits related to mature size were redefined as residual traits after accounting for the nonlinear relationships among mature size, growth and feed intake traits following mammalian size scaling rules. The base model, which incorporates average returns and costs under production and marketing systems typical of eastern Canada, is described. Economic values in the base model suggest that calf survival, fertility, residual feed intake, and dressing percentage are of primary economic importance in a purebreeding system. These traits also ranked highly in dam lines and (with the exception of fertility) in sire lines in terminal crossbreeding systems. Key words: Beef cattle, economic values, bioeconomic model

Two thousand three hundred and five bulls with complete pedigree information and proofs (ETA) in at least 1 of 10 yr for milk, fat and fat percent were used to study the reliability of genetic evaluations. No evidence was found that bulls with superior genetic evaluations failed to pass on this superiority to their sons and maternal grandsons. The assumption that all the genes controlling these quantitative traits are autosomes seems to be reasonable. Key words: Dairy cattle, genetic evaluation, bias

Nine male and nine female Beagle dogs were divided into three groups and administered orally 0, 15, or 30 mg/kg/day of the antidepressant compound MDL 19,660(5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3H-1,2,4-triazole-3-t hione) for 3 months to determine the long-term effects on hemopoietic cells. Compared to a control platelet range of 353,000-452,000/microliters, a thrombocytopenia reached lowest mean levels of 135,000/microliters in the 15 mg/kg/day dogs after 2 weeks and 81,000/microliters in the 30 mg/kg/day dogs after 1 week. Subsequently, platelet numbers progressively increased and by the end of the study averaged 222,000/microliters and 203,000/microliters in dogs administered 15 and 30 mg/kg/day. Ultrastructural study of the platelet increase in the 30 mg/kg/day dogs revealed more smaller discoid platelets but no change in percentage platelets with vacuolar degeneration. Histologically, megakaryocyte hyperplasia was present in the sternal marrows and spleens of treated dogs. These observations suggest that increased thrombopoiesis rather than reduced destruction was involved in this partial recovery of platelet numbers during continuous treatment. Concurrently, cyclic formation of reticulocytes and Heinz bodies occurred in dogs given 30 mg/kg/day of MDL 19,660. These dogs had slightly lower erythrocyte counts, hemoglobin levels, and hematocrits in association with hemosiderosis (spleen, liver), extramedullary hematopoiesis (spleen), and bone marrow hypercellularity. These findings indicate that both destructive and regenerative processes followed MDL 19,660-induced Heinz body formation.

Since domestication, livestock have evolved and been actively selected for adaptation to a wide range of physical, climatic, disease challenge and production environments. Relatively free access to these farm animal genetic resources (FAnGR) has delivered large benefits to developed and developing countries, notwithstanding examples of inappropriate promotion and use of specialised breeds in the developing world. Rapid changes in economic and agricultural environments globally are creating major threats to livestock diversity. The problem is most acute in the developing world, where information about the characteristics and status of indigenous FAnGR is limited and there is little or no capacity to protect such genetic resources. Recent international fora have recognised the need for urgent action to conserve FAnGR of the developing world. Priority is given to conservation through sustainable use but an urgent need for cryo-conservation is now recognised, overturning the consensus arrived at last decade that cryo-conservation was neither required nor desirable. Implementing conservation of developing world FAnGR will require regional and international collaboration and support, mechanisms for which have yet to be developed. With the accelerating rates of change in the developing world, failure to implement conservation and sustainable utilisation programs in the developing world in the very near future will likely lead to the loss of a substantial proportion of the world’s FAnGR.

Two-week oral administration of MDL-19,660, a triazole antidepressant compound, resulted in a dose-related thrombocytopenia in rats given 40–360 mg/kg d and dogs treated with 5–50 mg/kg d . Consumptive loss of platelets was not apparent since splenomegaly, hemorrhage, microscopic thrombi or prolonged coagulation times (prothrombin and activated partial thromboplastin) were not observed. Platelet production did not appear to be impaired since megakaryocytes in the bone marrow of treated animals were similar in number or slightly increased compared to control animals. Although the pathogenesis of this thrombocytopenia is presently unknown, intravascular destruction by immune mechanisms or direct drug-related effects seems most likely.

After 2 days of dosing, platelet counts progressively declined in dogs treated orally with 30 mg/kg/day of the antidepressant compound MDL 19,660 for 8 days. Accompanying the decrease in platelet counts was an increase in both large and vacuolated degenerating platelets. Upon cessation of dosing, the platelet counts returned to levels equal to or exceeding predosing levels within 4–7 days. Co-administration with aspirin, a known antiaggregating agent, had no protective effect on the drug-induced thrombocytopenia. In vitro testing of normal canine platelets in the presence of MDL 19,660 further revealed that spontaneous aggregation did not occur and that ADP-induced aggregation was inhibited. Drug-related platelet loss was also not prevented by the co-administration of prednisone, a steroid with immunosuppressive effects and inhibitory properties against reticuloendothelial cell phagocytosis of platelets. The results of the present investigation indicate that MDL 19,660 may produce in the dog a reversible thrombocytopenia in the form of vacuolar degeneration and subsequent destruction of the platelet by means other than aggregation or steroid-responsive mechanisms.

The GABA-transaminase inhibitor, vigabatrin, has been shown to have a rather low degree of acute toxicity in several animal species. Oral administration of the drug at 1,000 mg/kg/day for 2-4 weeks caused decreased food consumption and weight loss with resultant prostration and death in both rats and dogs. Dosages of 200 mg/kg/day were tolerated for a year without clinical signs in dogs, although rats suffered reduced weight gains and convulsions after 3-4 months when given the drug in the diet. The convulsions continued to occur frequently throughout the one-yr study, but abated 3-4 months after cessation of treatment. The only consistent histopathologic evidence of toxicity in rats and dogs has been the finding of intramyelinic edema (microvacuolation) in the brain, most notably in certain areas of white matter (cerebellum, reticular formation and optic tract in rats and columns of fornix and optic tract in dogs). No lesions were found in the spinal cord or peripheral nervous system. It took several weeks for the microvacuolation to develop, even at high dosages, but it did not continue to progress thereafter, even though a slight effect was noted at dosages as low as 30-50 mg/kg/day after one yr of treatment. The intramyelinic edemia disappeared within a few weeks after treatment was withdrawn. No residual effects were observed in dogs, whereas rats exhibited swollen axons and microscopic mineralized bodies in the cerebellum. Monkeys exhibited no adverse clinical effects except for occasional loose stools at 300 mg/kg/day. After 16 months of oral treatment at 300 mg/kg/day any suggestion of intramyelinic edema was considered to be equivocal, and there was no evidence of any effect in the 50 or 100 mg/kg/day monkeys after 6 yr of treatment. Higher doses caused chronic diarrhea, thus limiting the dosage in this species. Vigabatrin was shown to be well absorbed in rat, dog and man, whereas dose-limited absorption occurred in the monkey. Metabolism is practically nil in all 4 species and the primary elimination pathway is by glomerular filtration. Because vigabatrin is an irreversible inhibitor of GABA-transaminase and the enzyme has a slow turnover rate, plasma levels of the drug are not indicative of its pharmacologic activity. For this reason cerebrospinal fluid levels of GABA and vigabatrin were evaluated, with considerable species differences being noted. The significance of these differences in relation to the differences in toxic response is discussed.

Vigabatrin (VGB) causes intramyelinic edema (microvacuolation) in brain of dogs and rodent, which has encouraged development of noninvasive methods to monitor for this effect during clinical trials. We report the qualitative ex vivo magnetic resonance imaging (MRI) changes observed in a neuropathology study in dogs to detect time of onset and regression of VGB-induced intramyelinic edema. Beagles were randomly assigned to 18 groups of 6 dogs per group and administered vigabatrin orally (p.o.) at a dose of 300 mg/kg/day (2 males, 2 females) or placebo (1 male, 1 female). Animals were killed and examined at weekly intervals during the 12 weeks of treatment and at 1, 2, 4, 8, 12, and 16 weeks after discontinuation of drug treatment. Myelin microvacuolation in thalamus, hypothalamus, and fornix were noted histologically after 4-5 weeks of treatment. Increases in MRI T2 intensity were observed in hypothalamus after 4 weeks and in thalamus and columns of the fornix after 7 weeks. Both MRI T2 intensity and microvacuolation continued to increase during 12-week VGB treatment. When VGB treatment was discontinued after 12 weeks, both MRI T2 intensity and microvacuolation began to decrease. Sixteen weeks after VGB discontinuation, histopathology had returned to normal and MRI examination demonstrated a marked trend toward reversal of the increased T2 signal intensity. MRI thus has potential as a noninvasive surveillance technique in certain experimental and clinical conditions associated with intramyelinic edema.

Effecting genetic improvement requires genetic variation, a mechanism of selection, and an economic incentive for the improvement. Limited data suggest that there is within-breed genetic variation in milk fat composition, but accurate estimates are lacking. There is some evidence for modest differences among breeds. Substantial differences exist among species, indicating that substantial genetic change in fat composition is biologically possible. The economic incentives for genetic change are not clear. Changes in fat composition that would improve the quality of one milk product would often be detrimental to other products. Such changes would best work where subpopulations produced milk for specific end products. Such division of the industry would be difficult to organize and might impede existing improvement programs. Changes in fat composition that increased consumer acceptance of milk products, such as reduced saturated fat concentration, might increase the market for milk products. However, only large changes in composition are likely to affect consumer acceptance; thus, the gradual changes of conventional genetic improvement would produce little or no return to the breeder. Genetic changes that reduced processing costs or increased product value might have low to moderate economic value, inducing slow rates of change. Production of transgenic animals might provide a route for genetic alteration of fat composition in the future. Such improvement would most likely be cost effective in a subdivided production industry in which milk from cows of a particular genotype can be directed to a particular milk product. It is concluded that although alteration of fat composition could be achieved, it is unlikely to be an important component of genetic improvement of dairy cattle.

Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions. Histologic changes are most notable in the columns of the fornix and regions of the hypothalamus, thalamus, optic tract, and hippocampus. In an attempt to image these changes in vivo, we performed high-field MRI on seven treated and four control dogs at baseline and after 15 weeks of dosing with vigabatrin (300 mg/kg/d). All dogs underwent parallel electrophysiologic assessment to determine the effects of vigabatrin on afferent conduction. At 15 weeks, all treated dogs showed increased T2- and decreased T1-weighted signals, with changes from baseline most prominent in the columns of the fornix and to a lesser degree in the surrounding hypothalamus and thalamus. MRIs performed on control dogs were unremarkable. We then perfused a random selection of four treated and two control dogs and imaged their brains ex vivo prior to sectioning. Ex vivo imaging confirmed the in vivo findings and strongly correlated with both electrophysiologic and subsequent histopathologic findings. Imaging was repeated in the surviving dogs 5 and 12 weeks after discontinuation of dosing. Signal abnormalities in the treated dogs progressively diminished during recovery, paralleling the electrophysiologic and histopathologic results. These findings demonstrate that MRI can detect signal changes anatomically congruent with vigabatrin-induced intramyelinic edema and suggest that MRI may provide a useful noninvasive tool for monitoring patients during clinical trials.

The carcinogenic potential of medroxalol hydrochloride, an antihypertensive agent with β1 adrenergic cardiac blocking properties, and β2 and some α1 vasodilating activity, was studied by dietary administration. Long Evans rats were treated for 2 years and CD-1 mice for 18 months at dosages of 0, 50, 250 or 500 mg/kg/day. Medroxalol did not produce any evidence of a tumorigenic effect in the Long Evans rat, but graying of pigmented hair was noted at 250 and 500 mg/kg/day and is probably related to melanin binding of the drug. In the CD-1 mouse, there was a dose related increase in uterine leiomyomas that was statistically significant ( p < 0.05) at doses of 250 and 500 mg/kg/day. The incidence at 50 mg/kg/day was not different from control. Endometrial stromal sarcomas were observed only in treated mice, and pairwise comparison with controls indicated a statistically significant difference ( p < 0.05) only at the lowest dosage (50 mg/kg/day). The latter finding may not be related to treatment since there was no dose response and the incidence in the two higher dose groups was neither statistically significant nor higher than occasionally seen in other control groups.

Distemper was produced experimentally in 12 gnotobiotic dogs with the Snyder Hill and Lederle strains of virus. Eight gnotobiotic dogs served as uninoculated controls. In the absence of other microorganisms, the only signs of disease were mild transient fever and leukopenia. The only macroscopic lesion was severe atrophy of the thymus. Microscopically all the lymphoid tissues underwent lymphoid depletion and reticular cell hyperplasia. Lesions appeared in the brain eight days after inoculation. The virus caused direct neuronal degeneration in the frontal cortex, only minimal lesions in the vicinity of the fourth ventricle and no demyelination. Infrequent inclusion bodies were found in neurons and in the reticular cells of the lymphoid tissues. No lesions were found in the lungs, stomach, urinary bladder, or skin.

Chlorotrianisene (CTA), diethylstilbestrol (DES), and conjugated equine estrogens (CEE) when administered to rats in the diet for two years produced qualitatively, but not quantitatively, similar effects which included: reduced body weight gain, partial hair loss, reduced gonadal and secondary sex organ activity, slight increase in adrenal weight, and occasional inguinal hernias in the males. Except for a mild reduction in the hemoglobin and hematocrit values of the high dose DES males and females, none of these estrogens produced any noticeable effect on hematology or clinical chemistry values or increased the incidence of degenerative changes. The most striking differences between CTA and the other two estrogens were related to their effects on the rat pituitary. High levels of DES and CEE increased the mortality rate by stimulating the development of pituitary tumors. In addition, these two estrogens increased the incidence of mammary tumors and/or shortened the time of their appearance. All levels of CTA reduced the normal mortality rate and also inhibited or prevented the normal development of pituitary and associated mammary tumors. Our interpretation of these data was that they did not reveal any direct toxic or carcinogenic effects of these estrogens per se. Except for the differences cited above, these changes were considered to have been the expected responses of rats to chronic estrogenic stimulation.

Bendectin ® (BDP), a therapeutic formulation used to control the nausea and vomiting often associated with pregnancy in women, is composed of equal parts of dicyclomine hydrochloride, an antispasmodic, doxylamine succinate, and antihistamine, and pyridoxine hydrochloride. Teratology studies in rabbits and reproduction studies in rats were conducted with BDP and two of its components, dicyclomine hydrochloride and doxylamine succinate. None of these materials appeared to have any deleterious effects on pregnancy maintenance, litter size, or fetal weight in the rabbit, except when toxic (100 mg/kg/day doxylamine or dicyclomine) levels were reached. Breeding, conception, pregnancy maintenance, litter size, and fetal weight were unaffected in the rat, although a mild dose-related decrease in neonatal weight gains occurred in pups from doxylamine- and dicyclomine-treated dams. Occasional malformed fetuses were noted; however, the incidence and types of malformation suggested that they were fortuitous rather than drug related. The results of these tests in animals are in agreement with data reported in a controlled survey of case records of pregnant women treated during the first trimester with BDP.

The advantages of using the rabbit in teratologic studies are enumerated, and a technique for their use is reported in which preexperimental care, induction of ovulation, artificial insemination, administration of test compound, and examination of the fetuses are described. With these methods the conception rate in Dutch-Belted rabbits was 82.4%, and the average number of corpora lutea, implantation sites, and litter size were similar to those reported for natural matings. A total of 1186 rabbit fetuses from eight different teratogenicity studies was examined for morphologic abnormalities. The incidence and type of abnormalities in both control and treated groups were similar, indicating that these compounds were not teratogenic in the rabbit. A total of 881 fetuses was examined for skeletal defects. Extra ribs occurred in 35.4% of the fetuses. The fifth sternebra was missing or atrophic 23.7% of the time, and the second sternebra was similarly affected 2.5% of the time. Other sternebrae were missing or atrophic less than 1% of the time. Missing and/or atrophic sternebrae occurred in 25.8% of the fetuses. Bipartite and/or asymmetrical sternebrae occurred in 1.7% of the fetuses, and fused sternebrae occurred in 1.5%. One fetus had fused fourth and fifth ribs, another had the right half of two vertebral bodies fused. No visceral abnormalities were detected in 305 fetuses that were sectioned. Bipartite, asymmetrical, and fused sternebrae, although occurring infrequently, sometimes affected more than one kit in the same litter. Because of this, caution is required in interpreting such variations as drug-induced changes, even when several occur in a particular dose group. Such an occurrence can happen by chance alone. A review of available data indicated that neither thalidomide nor a corticosteroid (16-methyleneprednisolone) increased the incidence of these types of sternal variations. It is, therefore, concluded that if a drug is to be considered teratogenic in the rabbit, it should produce a dose-related incidence and pattern of malformations different than the normally expected variations described in this report.

The genetic relationships among carrier, fat, protein, and lactose will allow genetic alteration in any direction desired, although some changes would be much easier than others. Genetic parameters may vary somewhat between different populations, thus affecting the rates of different directions of change. In general, however, selection for an alteration in the fat:protein ratio would proceed rapidly, principally through alteration of fat concentration. Genetic alteration of composition is likely only if economic incentives for such change exist. Economic values, and therefore selection pressure, should be applied to amounts of components rather than concentrations. Recent developments in the theory of deriving economic weights for animal breeding indicate that selection indexes need to be reassessed. Although optimum breeding goals will vary somewhat, in most circumstances fat and protein yields and concentrations and the fat:protein ratio are likely to increase due to genetic selection. Only in the unlikely situation that fat has a very small or negative economic weight are other changes indicated. Lactose concentrations are unlikely to change much in any situation. Genetic variation in the composition of fat and protein, while of biological interest, is unlikely to be of more than minor importance in genetic improvement.

Medroxalol hydrochloride is an antihypertensive agent with β1 adrenergic cardiac blocking properties, and β2 and some α1 vasodilating activity. In previous carcinogenicity studies medroxalol was shown to induce leiomyomas of the uterus in CD-I mice but not in Long Evans rats. In addition, there was a significant increase in endometrial stromal sarcomas in mice receiving the lowest dose of medroxalol; however, the*** lack of a dose response made the relationship to treatment questionable. Because of these findings, additional 18-month drug diet studies were conducted in 3 parallel segments using female CD-1 mice to determine the effects of: 1) an expanded range of doses, 2) various durations of dosing, and 3) the effect of the β-blocker, propranolol, on leiomyoma induction. These studies confirmed the fact that chronic dietary treatment with medroxalol can lead to an increased incidence of leiomyomas in the mouse uterus, but failed to demonstrate any relationship between endometrial stromal sarcomas and medroxalol administration. A linear trend occurred in the incidence of leiomyomas and of smooth muscle hypertrophy/hyperplasia, a possible precursor to leiomyoma. Both findings were notably increased at 250 mg/kg/day or more. Doses of 50 mg/kg/day or less were considered no effect levels. At 500 mg/kg/day a treatment period of 12 months or more was required before a noticeable increase in leiomyomas occurred in mice examined after 18 months. The β-blocker, propranolol, prevented this increase in leiomyomas, and led to the conclusion that the β2 agonist activity of medroxalol was involved in their induction. Propranolol did not block the spontaneous occurrence of these tumors.

The antibacterial compound α -(1,4-dioxido-3-methylquinoxalin-2-yl)- N -methylnitrone (DMNM), which was administered for a maximum period of 90 days, was given orally at 0, 7.5, 15.0 or 22.5 mg/kg/day for dogs; 0, 15, 50 or 100 mg/kg/day for rats; and 35 mg/kg/day for monkeys. Reduced food consumption and weight gain, depression, debility, and deaths occurred starting at doses (mg/kg/day) of 15 in dogs, 35 in monkeys and 50 in rats. Frequent emesis and occasional black, tarry feces were also observed in most treated dogs. Necropsy examinations revealed small, pale adrenal glands in rats given a dose of 50 mg/kg/day and gastrointestinal hemorrhage in dogs administered 15.0 or 22.5 mg/kg/day of DMNM. Microscopically, vacuolar degeneration of the canine, monkey and rat adrenal cortex was seen at all dosages and appeared to progress from the zona reticularis to the zona glomerulosa. In rats treated with 50 mg/kg/day of the drug chronic lesions of adrenal cortical fibrosis, atrophy, and nodular hyperplasia were also detected. The only other significant microscopic lesions consisted of mild testicular atrophy and occasional gastric erosions in dogs treated with 7.5 mg/kg/day of DMNM.

Summary In a controlled study of 1,082 ill children with fever, bed rest was not a decisive factor in favoring a return of the temperature to normal.

Subacute oral administration of an experimental analgesic compound, l-2-(1-methyl-2-piperidyl)-1,1-diphenylethyl propionate hydrochloride, to four species of animals produced a variety of toxicologic responses. Rats tolerated oral doses up to 100 mg/kg/day for periods of 1 or 2 months without adverse clinicopathologic effects. Pregnant rabbits tolerated oral doses up to 80 mg/kg/day for 8 days during the period of embryogenesis without adverse effects upon either the doe or her offspring. In contrast, daily oral doses of 30 mg/kg or more produced emesis, weight loss, depression, unconsciousness, and, occasionally, death in both dogs and monkeys, and higher dosages usually caused death. Liver function was impaired in dogs but not in monkeys, although intracytoplasmic structures compatible with myelin figures occurred in the hepatocytes in both species. In addition, several monkeys had areas of demyelination in the brain which involved the white tracts of the cerebral gyri. These variations in response to a test agent reemphasize species differences and the difficulty in extrapolating toxicity data from one species to another. Because of the complexity of these findings, the compound was withdrawn from consideration as a candidate for clinical trials in man.

Recently, two of our local physicians left this community to relocate elsewhere and two others died. Some of their patients came to me bringing their medical records. It was then necessary for me to translate the abbreviations that had been used. This experience, constantly repeated everywhere, brings up the question of the use of abbreviations. Despite the fact that all major medical dictionaries list the more conventional abbreviations used in records and histories, such as BMR, CNS , etc., many of the terms peculiar to pediatrics are not listed; and even for conventional abbreviations, many of us do not bother to look up the "standard" ones, but tend to "roll our own." As a result, all of us face a rather chaotic situation that could be serious when we try to translate a colleague's original hieroglyphics (or he, ours) to determine whether a child has had his tetanus toxoid (" TT " [?]) or

Background Animal trypanosomosis in sub-Saharan Africa is a major obstacle to livestock based agriculture. Control relies on drugs with increasing incidence of multiple-drug resistance. A previous mapping experiment in an F2 population derived from the indigenous trypanotolerant N’Dama cattle crossed to susceptible (Kenya)-Boran cattle under controlled challenge, uncovered a number of trypanotolerance QTL (T-QTL). The present study was to determine expression of N’Dama trypanotolerance in a backcross to the Boran under conditions of field challenge, and whether chromosomal regions associated with trypanotolerance in the F2 experiment showed similar effects in the BC population. Methods 192 backcross animals to the Boran were produced in six batches from June 2001 to December 2006. At one year of age animals were moved to the field and exposed to natural challenge over about one year in Southwest Kenya (Narok). The animals were individually recorded weekly for body weight, packed cell volume, parasitaemia score, and drug treatments, and were genotyped using 35 microsatellite markers spanning 5 chromosomes found in the F2 study to harbour T-QTL. Results The F1 were most trypanotolerant, Boran least, and BC intermediate. Females showed distinctly higher trypanotolerance than males. There was a positive correlation in the BC population between trypanotolerance and number of N’Dama origin marker alleles. QTL mapping revealed T-QTL distributed among all five targeted chromosomes, corresponding in part to the results obtained in the F2 experiment. Conclusions N’Dama origin trypanotolerance is expressed in a BC population under field conditions in proportion to N’Dama origin marker alleles. Consequently, marker assisted selection in such populations may be a means of increasing trypanotolerance, while retaining the desirable productive qualities of the recurrent parent.