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Context A thorough analysis of the reasons for culling was made to understand the phenotypic trend in herd life. In addition, identification of culling reasons could enable to develop a strategy for further evaluation of longevity in Australian dairy cows. Aims The aim of this study was to investigate the main causes of culling in Australian dairy herds and thereby to assess the trend of reason-specific culling over time. Methods Culling reasons in Australian dairy cattle were studied based on culling records from 1995 through 2016. A total of 2 452 124 individual cow culling observations were obtained from Datagene, Australia, of which 2 140 337 were Holstein and 311 787 were from Jersey cows. A binary logistic regression model was used to estimate effects of breed and age and the trend of a particular culling reason over time. Key results The most important culling reasons identified over the 21-year period were infertility (17.0%), mastitis (12.9%), low production (9.3%), sold for dairy purpose (6.4%) and old age (6.2%), whereas 37.4% were ‘other reasons not reported’. The average age at culling was nearly the same for Holstein (6.75 years) and Jersey (6.73 years) cows. The estimated age at culling was slightly increased for Holstein cows (by 3.7 days) and somewhat decreased for Jersey cows (by 11 days) over the last two decades. The probability of culling cows for infertility and low production was high in early parities and consistently declined as age advanced, and culling due to mastitis was higher in older cows. The trend of main culling reasons over time was evaluated, indicating that the probability of culling due to infertility has progressively increased over the years in both breeds, and culling for mastitis in Jersey cows has also increased. Culling of cows due to low production sharply decreased from 2.5 to –8% for Holstein and from 73 to 60% for Jersey cows over the 21-year period. Conclusions Culling age has changed only little in both breeds whereas culling reasons have changed over the last two decades, with low production becoming a less important reason for culling and infertility becoming more important for Holstein and Jersey breeds. Implications Due to changes of culling reasons, there could be a change in the meaning of survival over time as well. As a result, genetic correlation with survival and other traits might be changed and accuracy and bias of genetic evaluations could be affected.

Background India is the largest milk producer globally, with the largest proportion of cattle milk production coming from smallholder farms with an average herd size of less than two milking cows. These cows are mainly undefined multi-generation crosses between exotic dairy breeds and indigenous Indian cattle, with no performance or pedigree recording. Therefore, implementing genetic improvement based on genetic evaluation has not yet been possible. We present the first results from a large smallholder performance recording program in India, using single nucleotide polymorphism (SNP) genotypes to estimate genetic parameters for monthly test-day (TD) milk records and to obtain and validate genomic estimated breeding values (GEBV). Results The average TD milk yield under the high, medium, and low production environments were 9.64, 6.88, and 4.61 kg, respectively. In the high production environment, the usual profile of a lactation curve was evident, whereas it was less evident in low and medium production environments. There was a clear trend of an increasing milk yield with an increasing Holstein Friesian (HF) proportion in the high production environment, but no increase above intermediate grades in the medium and low production environments. Trends for Jersey were small but yield estimates had a higher standard error than HF. Heritability estimates for TD yield across the lactation ranged from 0.193 to 0.250, with an average of 0.230. The additive genetic correlations between TD yield at different times in lactation were high, ranging from 0.846 to 0.998. The accuracy of phenotypic validation of GEBV from the method that is believed to be the least biased was 0.420, which was very similar to the accuracy obtained from the average prediction error variance of the GEBV. Conclusions The results indicate strong potential for genomic selection to improve milk production of smallholder crossbred cows in India. The performance of cows with different breed compositions can be determined in different Indian environments, which makes it possible to provide better advice to smallholder farmers on optimum breed composition for their environment.

Efforts to improve dairy production in smallholder farming systems of East Africa over the past decade have had limited impact because of the lack of records on performance to guide targeted breeding programs. Estimates of genetic parameters in these systems are lacking. Using data generated through a project (“Germplasm for Dairy Development in East Africa”) in Kenya and a genomic relationship matrix from genotypic records, we examined the potential impact of different models handling contemporary groups or herd effects on estimates of genetic parameters using a fixed regression model (FRM) for test-day (TD) milk yields, and the covariance structure for TD milk yield at various stages of lactation for animals using a random regression model (RRM). Models in which herd groups were defined using production levels derived from the data fitted the data better than those in which herds were grouped depending on management practices or were random. Lactation curves obtained for animals under different production categories did not display the typical peak yield characteristic of improved dairy systems in developed countries. Heritability estimates for TD milk yields using the FRM varied greatly with the definition of contemporary herd groups, ranging from 0.05 ± 0.03 to 0.27 ± 0.05 (mean ± standard error). The analysis using the RRM fitted the data better than the FRM. The heritability estimates for specific TD yields obtained by the RRM were higher than those obtained by the FRM. Genetic correlations between TD yields were high and positive for measures within short consecutive intervals but decreased as the intervals between TD increased beyond 60 d and became negative with intervals of more than 5 mo. The magnitude of the genetic correlation estimates among TD records indicates that using TD milk records beyond a 60-d interval as repeated measures of the same trait for genetic evaluation of animals on smallholder farms would not be optimal. Although each individual smallholder farmer retains only a few animals, using the genomic relationship between animals to link the large number of farmers operating under specified environments provides a sufficiently large herd-group for which a breeding program could be developed.

Background The genetic structure of a diverse set of 15 Indian indigenous breeds and non-descript indigenous cattle sampled from eight states was examined, based on 777 k single nucleotide polymorphism (SNP) genotypes obtained on 699 animals, with sample sizes ranging from 17 to 140 animals per breed. To date, this is the largest and most detailed assessment of the genetic diversity of Indian cattle breeds. Results Admixture analyses revealed that 109 of the indigenous animals analyzed had more than 1% Bos taurus admixture of relatively recent origin. Pure indigenous animals were defined as having more than 99% Bos indicus ancestry. Assessment of the genetic diversity within and between breeds using principal component analyses, F statistics, runs of homozygosity, the genomic relationship matrix, and maximum likelihood clustering based on allele frequencies revealed a low level of genetic diversity among the indigenous breeds compared to that of Bos taurus breeds. Correlations of SNP allele frequencies between breeds indicated that the genetic variation among the Bos indicus breeds was remarkably low. In addition, the variance in allele frequencies represented less than 1.5% between the Indian indigenous breeds compared to about 40% between Bos taurus dairy breeds. Effective population sizes (Ne) increased during a period post-domestication, notably for Ongole cattle, and then declined during the last 100 generations. Although we found that most of the identified runs of homozygosity are short in the Indian indigenous breeds, indicating no recent inbreeding, the high FROH coefficients and low FIS values point towards small population sizes. Nonetheless, the Ne of the Indian indigenous breeds is currently still larger than that of Bos taurus dairy breeds. Conclusions The changes in the estimates of effective population size are consistent with domestication from a large native population followed by consolidation into breeds with a more limited population size. The surprisingly low genetic diversity among Indian indigenous cattle breeds might be due to their large Ne since their domestication, which started to decline only 100 generations ago, compared to approximately 250 to 500 generations for Bos taurus dairy cattle.

Several studies have evaluated computational methods that infer the haplotypes from population genotype data in European cattle populations. However, little is known about how well they perform in African indigenous and crossbred populations. This study investigates: (1) global and local ancestry inference; (2) heterozygosity proportion estimation; and (3) genotype imputation in West African indigenous and crossbred cattle populations. Principal component analysis (PCA), ADMIXTURE, and LAMP-LD were used to analyse a medium-density single nucleotide polymorphism (SNP) dataset from Senegalese crossbred cattle. Reference SNP data of East and West African indigenous and crossbred cattle populations were used to investigate the accuracy of imputation from low to medium-density and from medium to high-density SNP datasets using Minimac v3. The first two principal components differentiatedBos indicusfrom EuropeanBos taurusand AfricanBos taurusfrom other breeds. Irrespective of assuming two or three ancestral breeds for the Senegalese crossbreds, breed proportion estimates from ADMIXTURE and LAMP-LD showed a high correlation (r≥ 0.981). The observed ancestral origin heterozygosity proportion in putative F1 crosses was close to the expected value of 1.0, and clearly differentiated F1 from all other crosses. The imputation accuracies (estimated as correlation) between imputed and the real data in crossbred animals ranged from 0.142 to 0.717 when imputing from low to medium-density, and from 0.478 to 0.899 for imputation from medium to high-density. The imputation accuracy was generally higher when the reference data came from the same geographical region as the target population, and when crossbred reference data was used to impute crossbred genotypes. The lowest imputation accuracies were observed for indigenous breed genotypes. This study shows that ancestral origin heterozygosity can be estimated with high accuracy and will be far superior to the use of observed individual heterozygosity for estimating heterosis in African crossbred populations. It was not possible to achieve high imputation accuracy in West African crossbred or indigenous populations based on reference data sets from East Africa, and population-specific genotyping with high-density SNP assays is required to improve imputation.

Background Understanding the relationship between genetic admixture and phenotypic performance is crucial for the optimization of crossbreeding programs. The use of small sets of informative ancestry markers can be a cost-effective option for the estimation of breed composition and for parentage assignment in situations where pedigree recording is difficult. The objectives of this study were to develop small single nucleotide polymorphism (SNP) panels that can accurately estimate the total dairy proportion and assign parentage in both West and East African crossbred dairy cows. Methods Medium- and high-density SNP genotype data (Illumina BovineSNP50 and BovineHD Beadchip) for 4231 animals sampled from African crossbreds, African Bos taurus, European Bos taurus, Bos indicus, and African indigenous populations were used. For estimating breed composition, the absolute differences in allele frequency were calculated between pure ancestral breeds to identify SNPs with the highest discriminating power, and different combinations of SNPs weighted by ancestral origin were tested against estimates based on all available SNPs. For parentage assignment, informative SNPs were selected based on the highest minor allele frequency (MAF) in African crossbred populations assuming two Scenarios: (1) parents were selected among all the animals with known genotypes, and (2) parents were selected only among the animals known to be a parent of at least one progeny. Results For the medium-density genotype data, SNPs selected for the largest differences in allele frequency between West African indigenous and European Bos taurus breeds performed best for most African crossbred populations and achieved a prediction accuracy (r2) for breed composition of 0.926 to 0.961 with 200 SNPs. For the high-density dataset, a panel with 70% of the SNPs selected on their largest difference in allele frequency between African and European Bos taurus performed best or very near best across all crossbred populations with r2 ranging from 0.978 to 0.984 with 200 SNPs. In all African crossbred populations, unambiguous parentage assignment was possible with ≥ 300 SNPs for the majority of the panels for Scenario 1 and ≥ 200 SNPs for Scenario 2. Conclusions The identified low-cost SNP assays could overcome incomplete or inaccurate pedigree records in African smallholder systems and allow effective breeding decisions to produce progeny of desired breed composition.

Reliably identifying breed proportions in crossbred cattle in smallholder farms is a crucial step to improve mating decisions and optimizing management in these systems. High‐density genotype information is able to estimate higher‐order breed proportions accurately, but, are too expensive for mass application in smallholder systems. We used high‐density genotype information (777 k SNPs) of 623 crossbred cattle from India that had Holstein‐Friesian (HFX) and/or Jersey and indigenous breeds in their ancestry to select a smaller number of SNPs for breed proportion estimation. The accuracy of estimates obtained from panels with 100–500 SNP was compared to estimates based on all SNPs. Panels were selected for highest absolute allele frequency difference between exotic dairy versus indigenous Bos indicus, or between HFX versus Jersey breeds. A step‐wise pruning approach was developed showing that and increased physical distances between markers of 8.5 Mb improved breed proportion estimation compared to a standard 1 Mb distance. A panel of 500 SNPs optimized to estimate HFX versus Jersey versus indicine ancestry was able to estimate indicine breed proportions with r 2 = .991, HFX proportions with r 2 = .979 and Jersey proportions with r 2 = .949. The number of markers was a deciding factor in estimation accuracy, together with the distribution of markers across the genome.

Selection based on genomic predictions has become the method of choice for genetic improvement in dairy cattle. This offers huge opportunity for developing countries with little or no pedigree data, and preliminary studies have shown promising results. The African Dairy Genetic Gains (ADGG) project initiated a digital system of dairy performance data collection, accompanied by genotyping in Tanzania in 2016. Currently, ADGG has the largest body of dairy performance data generated in East Africa from a smallholder dairy system. This study examines the use of genomic best linear unbiased prediction (GBLUP) and single-step (ss)GBLUP for the estimation of genetic parameters and accuracy of genomic prediction for daily milk yield and body weight in Tanzania. The estimates of heritability for daily milk yield from GBLUP and ssGBLUP were essentially the same, at 0.12 ± 0.03. The heritability estimates for daily milk yield averaged over the whole lactation from random regression model (RRM) GBLUP or ssGBLUP were 0.22 and 0.24, respectively. The heritability of body weight from GBLUP was 0.24 ± 04 but was 0.22 ± 04 from the ssGBLUP analysis. Accuracy of genomic prediction for milk yield from a forward validation was 0.57 for GBLUP based on fixed regression model or 0.55 from an RRM. Corresponding estimates from ssGBLUP were 0.59 and 0.53, respectively. Accuracy for body weight, however, was much higher at 0.83 from GBLUP and 0.77 for ssGBLUP. The moderate to high levels of accuracy of genomic prediction (0.53-0.83) obtained for milk yield and body weight indicate that selection on the basis of genomic prediction is feasible in smallholder dairy systems and most probably the only initial possible pathway to implementing sustained genetic improvement programs in such systems.

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.

With the new opportunities from DNA technology, multitier breeding schemes have the potential to become more effective and more integrated. Integrated breeding schemes can also be better adapted to account for potential genotype by environment interactions (G × E) between tiers. In this case, phenotypic and genotype information from lower tiers becomes more valuable as it involves measurement of traits that directly represent the breeding objective. The objective of this study was to compare scenarios that represented different selection strategies and their economic effectiveness in fine-wool commercial sheep operations that exploit multitier breeding structures. Genomic selection (GS) applied in the multiplier and the commercial tier presented the largest additional revenue among all scenarios, as it resulted in the largest amount of genetic progress. The largest benefits from GS were outweighed by the genotyping costs, which made DNA parentage the most feasible strategy for the multiplier tier, resulting in the highest cumulative net present value (CNPV). The benefits of phenotypes and genotype information from the commercial environment were larger in the presence of G × E between the nucleus and the commercial tier. The CNPV was larger with a 50% reduction in genotyping costs, which increased the returns of GS scenarios by 2.7-fold on average. Higher selection intensity when selecting multiplier rams also resulted in larger benefits. In this case, returns for the breeding scheme were 3.5-fold higher when 33% of multiplier males were selected based on commercial information, compared to scenarios selecting 50% of the available multiplier rams. The benefits of collecting commercial phenotypes and genotypes were long term, which means that return on investment often took more than 10 years to be achieved, and were largely dependent on two-stage selection to reduce cost while maintaining selection efficiency and on the cost of a genotype test.

International audience; AbstractBackgroundThis study aimed at (1) comparing the accuracies of genomic prediction for parasite resistance in sheep based on whole-genome sequence (WGS) data to those based on 50k and high-density (HD) single nucleotide polymorphism (SNP) panels; (2) investigating whether the use of variants within quantitative trait loci (QTL) regions that were selected from regional heritability mapping (RHM) in an independent dataset improved the accuracy more than variants selected from genome-wide association studies (GWAS); and (3) comparing the prediction accuracies between variants selected from WGS data to variants selected from the HD SNP panel.ResultsThe accuracy of genomic prediction improved marginally from 0.16 ± 0.02 and 0.18 ± 0.01 when using all the variants from 50k and HD genotypes, respectively, to 0.19 ± 0.01 when using all the variants from WGS data. Fitting a GRM from the selected variants alongside a GRM from the 50k SNP genotypes improved the prediction accuracy substantially compared to fitting the 50k SNP genotypes alone. The gain in prediction accuracy was slightly more pronounced when variants were selected from WGS data compared to when variants were selected from the HD panel. When sequence variants that passed the GWAS -log10(pvalue)\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$- log_{10} (p\,value)$$\end{document} threshold of 3 across the entire genome were selected, the prediction accuracy improved by 5% (up to 0.21 ± 0.01), whereas when selection was limited to sequence variants that passed the same GWAS -log10(pvalue)\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$- log_{10} (p\,value)$$\end{document} threshold of 3 in regions identified by RHM, the accuracy improved by 9% (up to 0.25 ± 0.01).ConclusionsOur results show that through careful selection of sequence variants from the QTL regions, the accuracy of genomic prediction for parasite resistance in sheep can be improved. These findings have important implications for genomic prediction in sheep.

Background This study aimed at identifying genomic regions that underlie genetic variation of worm egg count, as an indicator trait for parasite resistance in a large population of Australian sheep, which was genotyped with the high-density 600 K Ovine single nucleotide polymorphism array. This study included 7539 sheep from different locations across Australia that underwent a field challenge with mixed gastrointestinal parasite species. Faecal samples were collected and worm egg counts for three strongyle species, i.e. Teladorsagia circumcincta, Haemonchus contortus and Trichostrongylus colubriformis were determined. Data were analysed using genome-wide association studies (GWAS) and regional heritability mapping (RHM). Results Both RHM and GWAS detected a region on Ovis aries (OAR) chromosome 2 that was highly significantly associated with parasite resistance at a genome-wise false discovery rate of 5%. RHM revealed additional significant regions on OAR6, 18, and 24. Pathway analysis revealed 13 genes within these significant regions (SH3RF1, HERC2, MAP3K, CYFIP1, PTPN1, BIN1, HERC3, HERC5, HERC6, IBSP, SPP1, ISG20, and DET1), which have various roles in innate and acquired immune response mechanisms, as well as cytokine signalling. Other genes involved in haemostasis regulation and mucosal defence were also detected, which are important for protection of sheep against invading parasites. Conclusions This study identified significant genomic regions on OAR2, 6, 18, and 24 that are associated with parasite resistance in sheep. RHM was more powerful in detecting regions that affect parasite resistance than GWAS. Our results support the hypothesis that parasite resistance is a complex trait and is determined by a large number of genes with small effects, rather than by a few major genes with large effects. Electronic supplementary material The online version of this article (10.1186/s12711-019-0479-1) contains supplementary material, which is available to authorized users.

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.

MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally regulate expression of mRNAs in many biological pathways. Liver plays an important role in the feed efficiency of animals and high and low efficient cattle demonstrated different gene expression profiles by microarray. Here we report comprehensive miRNAs profiles by next-gen deep sequencing in Angus cattle divergently selected for residual feed intake (RFI) and identify miRNAs related to feed efficiency in beef cattle. Two microRNA libraries were constructed from pooled RNA extracted from livers of low and high RFI cattle, and sequenced by Illumina genome analyser. In total, 23,628,103 high quality short sequence reads were obtained and more than half of these reads were matched to the bovine genome (UMD 3.1). We identified 305 known bovine miRNAs. Bta-miR-143, bta-miR-30, bta-miR-122, bta-miR-378, and bta-let-7 were the top five most abundant miRNAs families expressed in liver, representing more than 63% of expressed miRNAs. We also identified 52 homologous miRNAs and 10 novel putative bovine-specific miRNAs, based on precursor sequence and the secondary structure and utilizing the miRBase (v. 21). We compared the miRNAs profile between high and low RFI animals and ranked the most differentially expressed bovine known miRNAs. Bovine miR-143 was the most abundant miRNA in the bovine liver and comprised 20% of total expressed mapped miRNAs. The most highly expressed miRNA in liver of mice and humans, miR-122, was the third most abundant in our cattle liver samples. We also identified 10 putative novel bovine-specific miRNA candidates. Differentially expressed miRNAs between high and low RFI cattle were identified with 18 miRNAs being up-regulated and 7 other miRNAs down-regulated in low RFI cattle. Our study has identified comprehensive miRNAs expressed in bovine liver. Some of the expressed miRNAs are novel in cattle. The differentially expressed miRNAs between high and low RFI give some insights into liver miRNAs regulating physiological pathways underlying variation in this measure of feed efficiency in bovines.

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.

Gastrointestinal (GI) parasitic infection is the main health constraint for small ruminant production, causing loss of weight and/or death. Red Maasai sheep have adapted to a tropical environment where extreme parasite exposure is a constant, especially with highly pathogenic Haemonchus contortus. This breed has been reported to be resistant to gastrointestinal parasite infection, hence it is considered an invaluable resource to study associations between host genetics and resistance. The aim of this study was to identify polymorphisms strongly associated with host resistance in a double backcross population derived from Red Maasai and Dorper sheep using a SNP-based GWAS analysis. The animals that were genotyped represented the most resistant and susceptible individuals based on the tails of phenotypic distribution (10% each) for average faecal egg counts (AVFEC). AVFEC, packed cell volume (AVPCV), and live weight (AVLWT) were adjusted for fixed effects and co-variables, and an association analysis was run using EMMAX. Revised significance levels were calculated using 100,000 permutation tests. The top five significant SNP markers with - log10 p-values >3.794 were observed on five different chromosomes for AVFEC, and BLUPPf90/PostGSf90 results confirmed EMMAX significant regions for this trait. One of these regions included a cluster of significant SNP on chromosome (Chr) 6 not in linkage disequilibrium to each other. This genomic location contains annotated genes involved in cytokine signalling, haemostasis and mucus biosynthesis. Only one association detected on Chr 7 was significant for both AVPCV and AVLWT. The results generated here reveal candidate immune variants for genes involved in differential response to infection and provide additional SNP marker information that has potential to aid selection of resistance to gastrointestinal parasites in sheep of a similar genetic background to the double backcross population.

Residual feed intake (RFI) has been adopted in Australia for the purpose of genetic improvement in feed efficiency in beef cattle. RFI is the difference between the observed feed intake of an animal and the predicted feed intake based on its size and growth rate over a test period. Gene expression of eight candidate genes (AHSG, GHR, GSTM1, INHBA, PCDH19, S100A10, SERPINI2 and SOD3), previously identified as differentially expressed between divergent lines of high- and low-RFI animals, was measured in an unselected population of 60 steers from the Angus Society Elite Progeny Test Program using quantitative real-time PCR. Results showed that the levels of gene expression were significantly correlated with RFI. The genes explain around 33.2% of the phenotypic variance in RFI, and prediction equations using the expression data are reasonably accurate estimators of RFI. The association of these genes with economically important traits, such as other feed efficiency-related traits and fat, growth and carcass traits, was investigated as well. The expression of these candidate genes was significantly correlated with feed conversion ratio and daily feed intake, which are highly associated with RFI, suggesting a functional role for these genes in modulating feed utilisation. The expression of these genes did not show any association with average daily gain, eye muscle area and carcass composition.

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.

Meat quality traits are the most economically important traits affecting the beef industry in Korea. We performed a whole genome quantitative trait locus (QTL) mapping study of carcass data in Hanwoo Korean cattle. Two hundred sixty-six Hanwoo steers from 65 sires were genotyped using a 10K Affymetrix SNP chip. The average SNP interval across the bovine genome was 1.5Mb. Associations between each individual SNP and four carcass traits [carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT), and marbling (MAR)] were assessed using a linear mixed model of each trait. Combined linkage and linkage disequilibrium analysis (LDLA) detected six potential QTL on BTA04, 06, 13, 16, 17, and 23 at the chromosome-wise level (P

African bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa. Some African Bos taurus breeds are highly tolerant of infection, but the potentially more productive Bos indicus zebu breeds are much more susceptible. Zebu cattle are well adapted for plowing and haulage, and increasing their tolerance of trypanosomiasis could have a major impact on crop cultivation as well as dairy and beef production. We used three strategies to obtain short lists of candidate genes within QTL that were previously shown to regulate response to infection. We analyzed the transcriptomes of trypanotolerant N'Dama and susceptible Boran cattle after infection with Trypanosoma congolense. We sequenced EST libraries from these two breeds to identify polymorphisms that might underlie previously identified quantitative trait loci (QTL), and we assessed QTL regions and candidate loci for evidence of selective sweeps. The scan of the EST sequences identified a previously undescribed polymorphism in ARHGAP15 in the Bta2 trypanotolerance QTL. The polymorphism affects gene function in vitro and could contribute to the observed differences in expression of the MAPK pathway in vivo. The expression data showed that TLR and MAPK pathways responded to infection, and the former contained TICAM1, which is within a QTL on Bta7. Genetic analyses showed that selective sweeps had occurred at TICAM1 and ARHGAP15 loci in African taurine cattle, making them strong candidates for the genes underlying the QTL. Candidate QTL genes were identified in other QTL by their expression profile and the pathways in which they participate.

Summary A genome-wide scan for quantitative trait loci (QTL) affecting gastrointestinal nematode resistance in sheep was completed using a double backcross population derived from Red Maasai and Dorper ewes bred to F1 rams. This design provided an opportunity to map potentially unique genetic variation associated with a parasite-tolerant breed like Red Maasai, a breed developed to survive East African grazing conditions. Parasite indicator phenotypes (blood packed cell volume – PCV and faecal egg count – FEC) were collected on a weekly basis from 1064 lambs during a single 3-month post-weaning grazing challenge on infected pastures. The averages of last measurements for FEC (AVFEC) and PCV (AVPCV), along with decline in PCV from challenge start to end (PCVD), were used to select lambs (N = 371) for genotyping that represented the tails (10% threshold) of the phenotypic distributions. Marker genotypes for 172 microsatellite loci covering 25 of 26 autosomes (1560.7 cm) were scored and corrected by Genoprob prior to qxpak analysis that included Box–Cox transformed AVFEC and arcsine transformed PCV statistics. Significant QTL for AVFEC and AVPCV were detected on four chromosomes, and this included a novel AVFEC QTL on chromosome 6 that would have remained undetected without Box–Cox transformation methods. The most significant P-values for AVFEC, AVPCV and PCVD overlapped the same marker interval on chromosome 22, suggesting the potential for a single causative mutation, which remains unknown. In all cases, the favourable QTL allele was always contributed from Red Maasai, providing support for the idea that future marker-assisted selection for genetic improvement of production in East Africa will rely on markers in linkage disequilibrium with these QTL.

Developed recently, high resolution melting (HRM) analysis is an efficient, accurate and inexpensive method for distinguishing DNA polymorphisms. HRM has been used to identify mutations in human genes, and to detect SNPs, INDELs and microsatellites in plants. However, its capacity to discriminate DNA variants in the context of complex haplotypes involving INDEL as well as SNP variants has not been examined until now. In this study, we genotyped an almond (Prunus dulcis (Mill.) D. A. Webb, syn. Prunus amygdalus Batsch) pseudo-testcross mapping population that showed segregation of complex haplotypes associated with CYP79D16 promoter sequence. The 175 bp region in question included a 7 bp INDEL and 3 SNPs, and manifested as three different haplotypes in the parents. Thus, with one homozygous and one heterozygous parent, two relevant genotypes were identified in the mapping population. Although the population displayed monomorphism with respect to the INDEL and one of the SNPs, HRM was sufficiently sensitive to distinguish genotypes on the basis of the two informative SNPs, and the resulting data were used to map CYP79D16 to linkage group 6 of the almond genome. Thus the capacity of HRM to resolve genotypes arising from complex haplotypes has been demonstrated, and this has important implications for the design of efficient HRM markers for various genetic applications including mapping, population studies and biodiversity analyses.

High resolution melting curve (HRM) is a recent advance for the detection of SNPs. The technique measures temperature induced strand separation of short PCR amplicons, and is able to detect variation as small as one base difference between samples. It has been applied to the analysis and scan of mutations in the genes causing human diseases. In plant species, the use of this approach is limited. We applied HRM analysis to almond SNP discovery and genotyping based on the predicted SNP information derived from the almond and peach EST database. Putative SNPs were screened from almond and peach EST contigs by HRM analysis against 25 almond cultivars. All 4 classes of SNPs, INDELs and microsatellites were discriminated, and the HRM profiles of 17 amplicons were established. The PCR amplicons containing single, double and multiple SNPs produced distinctive HRM profiles. Additionally, different genotypes of INDEL and microsatellite variations were also characterised by HRM analysis. By sequencing the PCR products, 100 SNPs were validated/revealed in the HRM amplicons and their flanking regions. The results showed that the average frequency of SNPs was 1:114 bp in the genic regions, and transition to transversion ratio was 1.16:1. Rare allele frequencies of the SNPs varied from 0.02 to 0.5, and the polymorphic information contents of the SNPs were from 0.04 to 0.53 at an average of 0.31. HRM has been demonstrated to be a fast, low cost, and efficient approach for SNP discovery and genotyping, in particular, for species without much genomic information such as almond.

Se propone una utilizacion sostenible de los recursos zoogeneticos para la agricultura y la alimentacion como mejor estrategia para el mantenimiento de su diversidad. Alcanzar el uso sostenible contribuira a la mejora de la calidad de vida y minimizara el riesgo a largo plazo de la supervivencia de las poblaciones animales. El concepto de utilizacion sostenible conlleva dimensiones economicas, ambientales y socioculturales. La utilizacion sostenible de los recursos zoogeneticos tambien contribuye a la seguridad alimentaria, el desarrollo rural, el aumento de oportunidades de empleo y la mejora de los estandares de vida de los ganaderos. Apoyar la cria de razas a traves de una mejor infraestructura, servicios, cuidados sanitarios de los animales, oportunidades de mercado y otras intervenciones contribuiria de forma significativa a la utilizacion sostenible de los recursos zoogeneticos. La utilizacion sostenible comporta el uso y mejora de las razas que poseen altos niveles de adaptacion de su forma fisica a los principales ambientes. Tambien conlleva el despliegue de principios geneticos adecuados para el desarrollo sostenible de las razas y la intensificacion sostenible de los sistemas de produccion en si mismos. La utilizacion sostenible y la mejora genetica se basan en el acceso a un amplia gama de recursos geneticos. Los programas de mejora genetica necesitan ser considerados en terminos de agricultura nacional y desarrollo de objetivos ganaderos, asi como compatibilidad con las condiciones locales y seguridad de sustento y sostenibilidad ambientales. La mejora genetica puede implicar la eleccion de las razas mas apropiadas, la raza mas pura adecuada o un sistema de cruce de razas y la aplicacion de mejora genetica dentro de la raza. La eleccion de la raza adecuada y de los sistemas de cruces de razas en los paises en via de desarrollo ha sido uno de los factores que mas ha influido en el incremento de la productividad, y se ha beneficiado ampliamente del hecho que en los paises desarrollados los recursos zoogeneticos estan bien caracterizados y gozan de un intercambio relativamente libre. Donde se han seguido los pasos adecuados con evaluaciones correctas sobre la demanda, ejecucion, consigna, impacto y analisis de costo-beneficio, el exito de la mejora dentro de la raza ha sido alcanzado con poblaciones indigenas en paises en via de desarrollo. Los objetivos de mejora y los programas para la subsistencia y sistemas pastorales seran mayormente distintos de los programas convencionales. Los cruces de razas han tenido mayor exito donde se ha seguido un programa de seleccion riguroso que implique la participacion de ganaderos y parte substancial del sector publico en forma de inversion y soporte tecnico. En todo programa de mejora genetica es necesario controlar y monitorear la consanguinidad. La mejora genetica dentro de la raza es una practica normal en el mundo desarrollado y se ha convertido una empresa altamente tecnica que cubre los campos de reproduccion, control, computo y tecnologias de genoma. Las nuevas tecnologias de genoma prometen la capacidad para identificar mejor y la utilizacion y mejora de los recursos zoogeneticos del mundo en via de desarrollo en un futuro proximo. Los sistemas utiles pueden sin embargo ser establecidos sin la necesidad de aplicar procedimientos o tecnologias de vanguardia.

A marker-assisted introgression (MAI) experiment was conducted to transfer trypanotolerance quantitative trait loci (QTL) from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. The objective was to assess the effect of three previously identified chromosomal regions on mouse chromosomes 1 (MMU1), 5 (MMU5) and 17 (MMU17) in different genetic backgrounds on the survival pattern following infection with Trypanosoma congolense. An exploratory data analysis revealed a biphasic pattern of time to death, with highly distinct early and late mortality phases. In this paper, we present survival analysis methods that account for the biphasic mortality pattern and results of reanalyzing the data from the MAI experiment. The analysis with a Weibull mixture model confirmed the biphasic pattern of time to death. Mortality phase, an unobserved variable, appears to be an important factor influencing survival time and is modeled as a binary outcome variable using logistic regression analysis. Accounting for this biphasic pattern in the analysis reveals that a previously observed sex effect on average survival is rather an effect on proportion of mice in the two mortality phases. The C57BL/6 (donor) QTL alleles on MMU1 and MMU17 act dominantly in the late mortality phase while the A/J (recipient) QTL allele on MMU17 acts dominantly in the early mortality phase. From this study, we found clear evidence for a biphasic survival pattern and provided models for its analysis. These models can also be used when studying defense mechanisms against other pathogens. Finally, these approaches provide further information on the nature of gene actions.

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.

To examine differences in cytokine profiles that may confer tolerance/susceptibility to bovine African trypanosomiasis, N'Dama (trypanotolerant, n = 8) and Boran (trypanosusceptible, n = 8) cattle were experimentally challenged with Trypanosoma congolense. Blood samples were collected over a 34-day period, and RNA was extracted from peripheral blood mononuclear cells. The expression levels of a panel of 14 cytokines were profiled over the time course of infection and between breeds. Messenger RNA (mRNA) transcript levels for the IL2, IL8, and IL1RN genes were significantly downregulated across the time course of infection in both breeds. There was an early increase in transcripts for genes encoding proinflammatory mediators ( IFNG, IL1A, TNF, and IL12) in N'Dama by 14 days postinfection (dpi) compared with preinfection levels that was not detected in the susceptible Boran breed. By the time of peak parasitemia, a type 2 helper T cells (TH2)-like cytokine environment was prevalent that was particularly evident in the Boran. Increases in transcripts for the IL6 (29 and 34 dpi) and IL10 (21, 25, and 29 dpi) genes were detected that were higher in the Boran compared with N'Dama. These findings highlight the implications for using murine models to study the bovine immune response to trypanosomiasis, where in some cases cytokine expression patterns differ. Overall, these data suggest that the trypanotolerant N'Dama are more capable of responding very early in infection with proinflammatory and TH1 type cytokines than the trypanosusceptible Boran and may explain why N'Dama control parasitemia more efficiently than Boran during the early stages of infection.

This study aimed to provide the foundation for an integrative approach to the identification of the mechanisms underlying the response to infection with Trypanosoma congolense, and to identify pathways that have previously been overlooked. We undertook a large-scale gene expression analysis study comparing susceptible A/J and more tolerant C57BL/6 mice. In an initial time course experiment, we monitored the development of parasitaemia and anaemia in every individual. Based on the kinetics of disease progression, we extracted total RNA from liver at days 0, 4, 7, 10 and 17 post infection and performed a microarray analysis. We identified 64 genes that were differentially expressed in the two strains in non-infected animals, of which nine genes remained largely unaffected by the disease. Gene expression profiling at stages of low, peak, clearance and recurrence of parasitaemia suggest that susceptibility is associated with high expression of genes coding for chemokines (e.g. Ccl24, Ccl27 and Cxcl13), complement components (C1q and C3) and interferon receptor alpha (Ifnar1). Additionally, susceptible A/J mice expressed higher levels of some potassium channel genes. In contrast, messenger RNA levels of a few immune response, metabolism and protease genes (e.g. Prss7 and Mmp13) were higher in the tolerant C57BL/6 strain as compared to A/J.

SUMMARY Since the publication of the mouse genome, attention has focused on the strains that were selected for sequencing. In this paper we report the results of experiments that characterized the response to infection with the murine gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J, C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well-characterized CBA (poor responder) and SWR (strong responder) as our controls. We employed the repeated infection protocol (consisting of 7 superimposed doses of 125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and 6 and assessment of worm burdens in week 6) that was used successfully to identify quantitative trait loci for genes involved in resistance to H. polygyrus . SWR, SJL and NIH mice performed indistinguishably and are confirmed as strong responder strains to H. polygyrus . CBA, C3H and A/J mice all tolerated heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J and BALB/c mice performed variably between experiments, some tolerating heavy worm burdens comparable to those in poor responders, and some showing evidence of resistance, although only in one experiment with female 129/J females and one with female BALB/c was the pattern and extent of worm loss much like that in SWR mice. Because the genetic relationships between six of the strains exploited in this study are now well-understood, our results should enable analysis through single nucleotide polymorphisms and thereby provide more insight into the role of the genes that control resistance to H. polygyrus.

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.

We developed an F(11) AIL population from an F(1) cross of A/J (susceptible) and C57BL/6J (resistant) mouse strains. One thousand F(11) mice were challenged with P.c. chabaudi 54X, and 340 mice selected from the phenotypic extremes for susceptibility and resistance were genotyped for microsatellite markers on Chromosomes (Chrs) 5, 8, and 17. QTL originally detected in backcross and F(2) populations were confirmed on the three chromosomes within narrower genomic regions, by maximum likelihood and regression analyses. Each of the previously mapped QTL on Chrs 5 and 17 resolved into two linked QTLs. The distal and proximal QTLs on Chrs 5 and 17, respectively, map to the previously reported QTL.

To evaluate the Weitzman approach for assessing alternative conservation strategies for breed (population) diversity, we used genetic distance measures between 49 African cattle breeds divided into two groups of 26 taurine ( Bos taurus ) and sanga ( Bos taurusBos indicus ) breeds and 23 zebu ( Bos indicus ) and zenga (sangaBos indicus ) breeds. The derived maximum-likelihood trees clearly displayed the geo- graphic distribution and the zebu-taurine admixture of the breeds. We developed a novel scheme to estimate the extinction probability for each breed which considered total population size, change of population size over the last 10 years, distribution of the breed, risk of indiscriminate crossing, organization among farmers, establishment of conservation schemes, political situation of the countries, special traits, sociocultural impor- tance, and reliability of information. This scheme yielded reasonable estimates of extinction probabilities for the analyzed breeds, which were significantly influenced by the population size and its recent change, distri- bution of the breed, organization among farmers, establishment of conservation schemes, and reliability of information. The average extinction probability over all breeds and for each breed group was around 48%. Diversity in the zebu-zenga group was only half the diversity in the taurine-sanga group, mainly because of the lower number of breeds and their genetic origin. For both groups, the expected diversity after 20-50 years was about half the current diversity, and the coefficient of variation was about 20%. Our results suggest that the optimum conservation strategy is to give priority to those breeds with the highest marginal diversity, rather than to the most endangered breeds; thus, Madagascar Zebu and Muturu should be given conserva- tion priority in their respective groups. Our study demonstrates that efficient conservation of genetic diversity with limited funds has to take genetic and nongenetic factors into account. Nongenetic factors are accounted for within our scheme to derive extinction probabilities. Within-breed and within-population diversity are not accounted for. Extending Weitzman's basic approach accordingly could yield an effective methodology for determining conservation strategies under highly varying circumstances and for many species, including wild organisms.

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.

Trypanosomosis, or sleeping sickness, is a major disease constraint on livestock productivity in sub-Saharan Africa. To identify quantitative trait loci (QTL) controlling resistance to trypanosomosis in cattle, an experimental cross was made between trypanotolerant African N'Dama ( Bos taurus ) and trypanosusceptible improved Kenya Boran ( Bos indicus ) cattle. Sixteen phenotypic traits were defined describing anemia, body weight, and parasitemia. One hundred seventy-seven F 2 animals and their parents and grandparents were genotyped at 477 molecular marker loci covering all 29 cattle autosomes. Total genome coverage was 82%. Putative QTL were mapped to 18 autosomes at a genomewise false discovery rate of 2 cross between N'Dama and Boran cattle could produce a synthetic breed with higher trypanotolerance levels than currently exist in the parental breeds.