Genome-wide association study of health and production traits in meat sheep.

Genotypes are currently widely used in animal breeding programmes to enhance the speed of genetic progress. With sufficient data, a Genome-Wide Association Study (GWAS) can be performed to identify informative markers. The aim of this study was to investigate the genetic background of health (footrot and mastitis) and production (birth weight, weaning weight, scan weight, and fat and muscle depth) traits using the available phenotypic and Single Nucleotide Polymorphism (SNP) data collected on the UK Texel sheep population. Initially, 10 193 genotypes were subject to quality control, leaving 9 505 genotypes for further analysis. Selected genotypes, recorded on four different Illumina chip types from low density (15 k SNPs) to high density (606 006 SNPs), were imputed to a subset of 45 686 markers from 50 k array, distributed on 27 chromosomes. Phenotypes collected on 32 farms across the UK for footrot and mastitis and extracted from the UK National database (iTexel) for the production traits were used along with pre-estimated variance components to obtain de-regressed breeding values and used to perform GWAS. Results showed three SNPs being significant on the genome-wise level ('OAR8_62240378.1' on chromosome 8 for birth weight, 's14444.1' on chromosome 19 for weaning weight and 's65197.1' on chromosome 23 for scan weight). Fourteen subsequent SNPs were found to be significant at the chromosome-wise level. These SNPs are located within or close to previously reported QTLs impacting on animal health (such as faecal egg count or somatic cell count) and production (such as body or carcass weight and fat amount). These results indicate that the studied traits are highly polygenic with complex genetic architecture.

Discovery of hidden pedigree errors combining genomic information with the genomic relationship matrix in Texel sheep.

Genomic variants such as Single Nucleotide Polymorphisms and animal pedigree are now used widely in routine genetic evaluations of livestock in many countries. The use of genomic information not only can be used to enhance the accuracy of prediction but also to verify pedigrees for animals that are extensively managed using natural mating and enabling multiple-sire mating groups to be used. By so doing, the rate of genetic gain is enhanced, and any bias associated with incorrect pedigrees is removed. This study used a set of 8 764 sheep genotypes to verify the pedigree based on both the conventional opposing homozygote method as well as a novel method when combined with the inclusion of the genomic relationship matrix (GRM). The genomic relationship coefficients between verified pairs of animals showed on average a relationship of 0.50 with parent, 0.25 with grandparent, 0.13 with great grandparent, 0.50 with full-sibling and 0.27 with half-sibling. Minimum obtained values from these verified pairs were then used as thresholds to determine the pedigree for unverified pairs of animals, to detect potential errors in the pedigree. Using a case study from a population partially genotyped UK sheep, the results from this study illustrate a powerful way to resolve parentage inconsistencies, when combining the conventional 'opposing homozygote' method using genomic information together with GRM for pedigree checking. In this way, previously undetected pedigree errors can be resolved.

Animal Board Invited Review: Meta-analysis of genetic parameters for resilience and efficiency traits in goats and sheep.

Genetic selection focused purely on production traits has proven very successful in improving the productive performance of livestock. However, heightened environmental and infectious disease challenges have raised the need to also improve the resilience of animals to such external stressors, as well as their efficiency in utilising available resources. A better understanding of the relationship between efficiency and production and health traits is needed to properly account for it in breeding programmes and to produce animals that can maintain high production performance in a range of environmental conditions with minimal environmental footprint. The aim of this study was to perform a meta-analysis of genetic parameters for production, efficiency and health traits in sheep and goats. The dataset comprised 963 estimates of heritability and 572 genetic correlations collated from 162 published studies. A threelevel meta-analysis model was fitted. Pooled heritability estimates for milk production traits ranged between 0.27 ± 0.03 and 0.48 ± 0.13 in dairy goats and between 0.21 ± 0.06 and 0.33 ± 0.07 in dairy sheep. In meat sheep, the heritability of efficiency traits ranged from 0.09 ± 0.02 (prolificacy) up to 0.32 ± 0.14 (residual feed intake). For health traits, pooled heritability was 0.07 ± 0.01 (faecal egg count) and 0.21 ± 0.01 (somatic cell score) in dairy goats and 0.14 ± 0.04 (faecal egg count) and 0.13 ± 0.02 (somatic cell score) in dairy sheep. In meat sheep, the heritability of disease resistance and survival traits ranged between 0.07 ± 0.02 (mastitis) and 0.50 ± 0.10 (breech strike). Pooled estimates of genetic correlations between resilience and efficiency traits in dairy goats were not significantly different from zero with the exception of somatic cell score and fat content (-0.19 ± 0.01). In dairy sheep, only the unfavourable genetic correlation between somatic cell score and protein content (0.12 ± 0.03) was statistically significant. In meat sheep only, the correlations between growth and faecal egg count (-0.28 ± 0.11) as well as between growth and dagginess (-0.33 ± 0.13) were statistically significant and favourable. Results of this meta-analysis provide evidence of genetic antagonism between production and health in dairy sheep and goats. This was not observed in meat sheep where most of the pooled estimates had high standard errors and were non-significant. Based on the obtained results, it seems feasible to simultaneously improve efficiency and health in addition to production by including the different types of traits in the breeding goal. However, a better understanding of potential trade-offs between these traits would be beneficial. Particularly, more studies focused on reproduction and resilience traits linked to the animal's multi-trait response to challenges are required.

Genome-wide association identifies methane production level relation to genetic control of digestive tract development in dairy cows.

The global temperatures are increasing. This increase is partly due to methane (CH4) production from ruminants, including dairy cattle. Recent studies on dairy cattle have revealed the existence of a heritable variation in CH4 production that enables mitigation strategies based on selective breeding. We have exploited the available heritable variation to study the genetic architecture of CH4 production and detected genomic regions affecting CH4 production. Although the detected regions explained only a small proportion of the heritable variance, we showed that potential QTL regions affecting CH4 production were located within QTLs related to feed efficiency, milk-related traits, body size and health status. Five candidate genes were found: CYP51A1 on BTA 4, PPP1R16B on BTA 13, and NTHL1, TSC2, and PKD1 on BTA 25. These candidate genes were involved in a number of metabolic processes that are possibly related to CH4 production. One of the most promising candidate genes (PKD1) was related to the development of the digestive tract. The results indicate that CH4 production is a highly polygenic trait.

New mastitis phenotypes suitable for genomic selection in meat sheep and their genetic relationships with udder conformation and lamb live weights.

Mastitis can prove expensive in sheep reared for meat production due to costs associated with treatment methods, poor lamb growth and premature culling of ewes. The most commonly used method to detect mastitis, in dairy systems, is somatic cell counts. However, in many meat-producing sheep flocks ewes are not routinely handled, thus regular milk sampling is not always possible. It is, therefore, worthwhile to investigate alternative phenotypes, such as those associated with udder conformation and methods of evaluating somatic cell counts in the milk, such as the California Mastitis Test. The main objectives of this study were therefore: (a) to estimate genetic parameters of traits relating to mastitis and udder conformation in a meat sheep breed; (b) estimate the level of association between somatic cell counts and the California Mastitis Test and (c) assess the relationships between mastitis and both udder conformation and lamb live weights. Data were collected from Texel ewes based on 29 flocks, throughout the UK, during 2015 and 2016. The ewes were scored twice each year, at mid- and late-lactation. Eight different conformation traits, relating to udder and teat characteristics, and milk samples were recorded. The data set comprised of data available for 2957 ewes. The pedigree file used contained sire and dam information for 31 775 individuals. The animal models used fitted relevant fixed and random effects. Heritability estimates for traits relating to mastitis (somatic cell score and the California Mastitis Test), ranged from 0.08 to 0.11 and 0.07 to 0.11, respectively. High genetic correlations were observed between somatic cell score and the California Mastitis Test (0.76 to 0.98), indicating the California Mastitis Test to be worthwhile for assessing infection levels, particularly at mid-lactation. The strongest correlations observed between the mastitis traits and the udder conformation traits were associated with udder depth (0.61 to 0.75) also at mid-lactation. Negative phenotypic correlations were estimated between mastitis and the weight of lamb reared by the ewe (-0.15 to -0.23), suggesting that lamb weights fell as infection levels rose. Genetic correlations were not significantly different from zero. Reducing mastitis will lead to improvements in flock productivity and the health and welfare of the animals. It will also improve the efficiency of production and the resilience to disease challenge. The economic benefits, therefore, of these results combined could be substantial not only in this breed but also in the overall meat sheep industry.

Pseudopregnancy and aseasonal breeding in dairy goats: genetic basis of fertility and impact on lifetime productivity.

Until recently, the main selection focus in UK dairy goats has been on milk yield. To develop a selection index suitably weighted for a variety of traits, it is important to understand the genetic relationships between production, health and fertility traits. This study focussed on three aspects of reproduction that are of interest to goat breeders. (1) Out of season (OOS) kidding ability: goats are highly seasonal breeders so achieving consistent, year-round dairy production presents a challenge. It may be possible to select for extended or shifted breeding cycles, however, there are no published studies on the genetic basis of seasonal kidding ability, and a genetic correlation with milk production in dairy goats; (2) age at first kidding (AFK): a reduced AFK offers the opportunity for more rapid genetic improvement, as well as reducing the amount of time and resources required to raise the animals to producing age; (3) pseudopregnancy (PPG): as it is difficult to diagnose pregnancy within 30 days of mating, high herd levels of PPG could add a significant delay in breeding replacement animals, or commencing a new lactation. Using records from 9546 goats, the objective of this study was to investigate the genetic relationships between the reproductive traits described above, and the production traits 520-day milk yield (MY520), lifetime milk yield (MYLife) and lifetime number of days in milk (DIMLife). The 'out of season' phenotype was defined as week of kidding relative to the 4 weeks of the year where the highest average number of births occur. Incidences of PPG that occurred during the first lactation were used as cases, while goats with none were assigned as controls. Relevant fixed and random effects were fitted in the models. In line with other reproduction traits, heritability estimates were low ranging from 0.08 to 0.11. A negative genetic correlation was found between AFK and MY520 (-0.22±0.10), whereas a positive genetic correlation was found between PPG and DIMLife (0.58±0.11). Pseudopregnancy and OOS were positively genetically correlated (0.36±0.15). All other genetic correlations were very low. The results of this study indicate that selection for the reproductive traits analysed is feasible, without adversely affecting MYLife.

Analysis of single nucleotide polymorphisms variation associated with important economic and computed tomography measured traits in Texel sheep.

Sheep are an important part of the global agricultural economy. Growth and meat production traits are significant economic traits in sheep. The Texel breed is the most popular terminal sire breed in the UK, mainly selected for muscle growth and lean carcasses. This is a study based on a genome-wide association approach that investigates the links between some economically important traits, including computed tomography (CT) measurements, and molecular polymorphisms in UK Texel sheep. Our main aim was to identify single nucleotide polymorphisms (SNP) associated with growth, carcass, health and welfare traits of the Texel sheep breed. This study used data from 384 Texel rams. Data comprised ten traits, including two CT measured traits. The phenotypic data were placed in four categories: growth traits, carcass traits, health traits and welfare traits. De-regressed estimated breeding values (EBV) for these traits together with sire genotypes derived with the Ovine 50 K SNP array of Illumina were jointly analysed in a genome wide association analysis. Eight novel chromosome-wise significant associations were found for carcass, growth, health and welfare traits. Three significant markers were intronic variants and the remainder intergenic variants. This study is a first step to search for genomic regions controlling CT-based productivity traits related to body and carcass composition in a terminal sire sheep breed using a 50 K SNP genome-wide array. Results are important for the further development of strategies to identify causal variants associated with CT measures and other commercial traits in sheep. Independent studies are needed to confirm these results and identify candidate genes for the studied traits.

Remote-control of the enantiomeric supramolecular recognition mediated by chiral azobenzenes bound to human serum albumin.

Three novel tyrosine-conjugated azobenzene molecules were designed and their ability to target a natural chiral host matrix (human serum albumin, HSA) was investigated. We found that the interplay between the spatial configuration of the chiral substituents and the change in local symmetry resulting from the photoisomerization process strongly affects the optical activity of the bound photochromes. In particular, the different signal amplification obtained upon binding of the photoswitches to the biopolymer enables obtaining a chirooptical system tunable over a wide range of wavelengths.

HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry.

Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non-European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA-DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an admixed/non-European PSC population carried this allele, suggesting that further assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03 in admixed or multi-ethnic populations could aid in identifying the causative allele.

Heritability of methane emissions from dairy cows over a lactation measured on commercial farms.

Methane emission is currently an important trait in studies on ruminants due to its environmental and economic impact. Recent studies were based on short-time measurements on individual cows. As methane emission is a longitudinal trait, it is important to investigate its changes over a full lactation. In this study, we aimed to estimate the heritability of the estimated methane emissions from dairy cows using Fourier-transform infrared spectroscopy during milking in an automated milking system by implementing the random regression method. The methane measurements were taken on 485 Polish Holstein-Friesian cows at 2 commercial farms located in western Poland. The overall daily estimated methane emission was 279 g/d. Genetic variance fluctuated over the course of lactation around the average level of 1,509 (g/d), with the highest level, 1,866 (g/d), at the end of the lactation. The permanent environment variance values started at 2,865 (g/d) and then dropped to around 846 (g/d) at 100 d in milk (DIM) to reach the level of 2,444 (g/d) at the end of lactation. The residual variance was estimated at 2,620 (g/d). The average repeatability was 0.25. The heritability level fluctuated over the course of lactation, starting at 0.23 (SE 0.12) and then increasing to its maximum value of 0.3 (SE 0.08) at 212 DIM and ending at the level of 0.27 (SE 0.12). Average heritability was 0.27 (average SE 0.09). We have shown that estimated methane emission is a heritable trait and that the heritability level changes over the course of lactation. The observed changes and low genetic correlations between distant DIM suggest that it may be important to consider the period in which methane phenotypes are collected.

Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study.

Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymorphisms (SNPs) and the association with a clinical phenotype. A previous GWAS performed in 300 renal transplant recipients identified two SNPs (rs3811321 and rs6565887) associated with serum creatinine and clinical outcome. We sought to validate these findings. Genotyping of the two SNPs was performed using Taqman assays in 1638 Caucasians participating in the Assessment of LEscol in Renal Transplant (ALERT) study. Primary endpoint was death-censored graft loss, and secondary endpoint was all-cause mortality. Applying Cox regression, no crude association to graft loss was found for rs3811321 on chromosome 14 (hazard ratio [HR] 0.87, 95% CI 0.59-1.29, p = 0.50) or rs6565887 on chromosome 18 (HR 0.88, CI 0.62-1.25, p = 0.48). Multivariable adjustments did not change results, nor did evaluation of the number of risk alleles formed by the two SNPs. No association with mortality was detected. In conclusion, an impact of two SNPs on chromosomes 14 and 18 on death-censored graft survival or all-cause mortality was not confirmed. Our results emphasize the importance of validating findings from high-throughput genetics studies and call for large collaborative research initiatives in the field of transplantation outcomes.

Genetic parameters of linear conformation type traits and their relationship with milk yield throughout lactation in mixed-breed dairy goats.

Conformation traits are of interest to many dairy goat breeders not only as descriptive traits in their own right, but also because of their influence on production, longevity, and profitability. If these traits are to be considered for inclusion in future dairy goat breeding programs, relationships between them and production traits such as milk yield must be considered. With the increased use of regression models to estimate genetic parameters, an opportunity now exists to investigate correlations between conformation traits and milk yield throughout lactation in more detail. The aims of this study were therefore to (1) estimate genetic parameters for conformation traits in a population of crossbred dairy goats, (2) estimate correlations between all conformation traits, and (3) assess the relationship between conformation traits and milk yield throughout lactation. No information on milk composition was available. Data were collected from goats based on 2 commercial goat farms during August and September in 2013 and 2014. Ten conformation traits, relating to udder, teat, leg, and feet characteristics, were scored on a linear scale (1-9). The overall data set comprised data available for 4,229 goats, all in their first lactation. The population of goats used in the study was created using random crossings between 3 breeds: British Alpine, Saanen, and Toggenburg. In each generation, the best performing animals were selected for breeding, leading to the formation of a synthetic breed. The pedigree file used in the analyses contained sire and dam information for a total of 30,139 individuals. The models fitted relevant fixed and random effects. Heritability estimates for the conformation traits were low to moderate, ranging from 0.02 to 0.38. A range of positive and negative phenotypic and genetic correlations between the traits were observed, with the highest correlations found between udder depth and udder attachment (0.78), teat angle and teat placement (0.70), and back legs and back feet (0.64). The genetic correlations estimated between conformation traits and milk yield across the first lactation demonstrated changes during this period. The majority of correlations estimated between milk yield and the udder and teat traits were negative. Therefore, future breeding programs would benefit from including these traits to ensure that selection for increased productivity is not accompanied by any unwanted change in functional fitness.

Rates of inbreeding and genetic adaptation for populations managed as herds in zoos with a rotational mating system or with optimized contribution of parents.

This study compares two genetic management scenarios for species kept in herds, such as deer. The simulations were designed so that their results can be extended to a wide range of zoo populations. In the first scenario, the simulated populations of size 3 × 20, 6 × 40 or 20 × 60 (herds × animals in herd) were managed with a rotational mating (RM) scheme in which 10%, 20% or 50% of males were selected for breeding and moved between herds in a circular fashion. The second scenario was based on optimal contribution theory (OC). OC requires an accurate pedigree to calculate kinship; males were selected and assigned numbers of offspring to minimize kinship in the next generation. RM was efficient in restriction of inbreeding and produced results comparable with OC. However, RM can result in genetic adaptation of the population to the zoo environment, in particular when 20% or less males are selected for rotation and selection of animals is not random. Lowest rates of inbreeding were obtained by combining OC with rotation of males as in the RM scheme. RM is easy to implement in practice and does not require pedigree data. When full pedigree is available, OC management is preferable.

Estimation of genomic breeding values for milk yield in UK dairy goats.

The objective of this study was to estimate genomic breeding values for milk yield in crossbred dairy goats. The research was based on data provided by 2 commercial goat farms in the UK comprising 590,409 milk yield records on 14,453 dairy goats kidding between 1987 and 2013. The population was created by crossing 3 breeds: Alpine, Saanen, and Toggenburg. In each generation the best performing animals were selected for breeding, and as a result, a synthetic breed was created. The pedigree file contained 30,139 individuals, of which 2,799 were founders. The data set contained test-day records of milk yield, lactation number, farm, age at kidding, and year and season of kidding. Data on milk composition was unavailable. In total 1,960 animals were genotyped with the Illumina 50K caprine chip. Two methods for estimation of genomic breeding value were compared-BLUP at the single nucleotide polymorphism level (BLUP-SNP) and single-step BLUP. The highest accuracy of 0.61 was obtained with single-step BLUP, and the lowest (0.36) with BLUP-SNP. Linkage disequilibrium (r(2), the squared correlation of the alleles at 2 loci) at 50 kb (distance between 2 SNP) was 0.18. This is the first attempt to implement genomic selection in UK dairy goats. Results indicate that the single-step method provides the highest accuracy for populations with a small number of genotyped individuals, where the number of genotyped males is low and females are predominant in the reference population.

Estimation of genetic parameters for milk yield across lactations in mixed-breed dairy goats.

Currently, breeding values for dairy goats in the United Kingdom are not estimated and selection is based only on phenotypes. Several studies from other countries have applied various methodologies to estimate breeding values for milk yield in dairy goats. However, most of the previous analyses were based on relatively small data sets, which might have affected the accuracy of the parameter estimates. The objective of this study was to estimate genetic parameters for milk yield in crossbred dairy goats in lactations 1 to 4. The research was based on data provided by 2 commercial goat farms in the United Kingdom comprising 390,482 milk yield records on 13,591 dairy goats kidding between 1987 and 2012. The population was created by crossing 3 breeds: Alpine, Saanen, and Toggenburg. In each generation, the best-performing animals were selected for breeding and, as a result, a synthetic breed was created. The pedigree file contained 28,184 individuals, of which 2,414 were founders. The data set contained test-day records of milk yield, lactation number, farm, age at kidding, and year and season of kidding. Data on milk composition was unavailable. Covariance components were estimated with the average information REML algorithm in the ASReml package (VSN International Ltd., Hemel Hempstead, UK). A random regression animal model for milk yield with fixed effects of herd test day, year-season, and age at kidding was used. Heritability was the highest at 200 and 250d in milk (DIM), reaching 0.45 in the first lactation and between 0.34 and 0.25 in subsequent lactations. After 300 DIM, the heritability started decreasing to 0.23 and 0.10 at 400 DIM in the first and subsequent lactations, respectively. Genetic correlation between milk yield in the first and subsequent lactations was between 0.16 and 0.88. This study found that milk yields in first and subsequent lactations are highly correlated, both at the genetic and phenotypic level. Estimates of heritability for milk yield were higher than most of the values reported in the literature, although they were in the range reported in this species. This should facilitate genetic improvement for the population studied as part of a broader multi-trait breeding program.

Short-term storage and swim-up selection do not affect the x/y ratio in equine spermatozoa.

The standard procedure of artificial insemination with fresh equine spermatozoa involves short-term storage (to 48 h at 5°C). This procedure is accompanied by a gradual loss of sperm viability. The aim of this study was to investigate whether the X/Y ratio of equine spermatozoa is affected by short-term storage and the swim-up procedure. We used a standard protocol, for short-term storage (0, 24 and 48 h at 5°C) of stallion semen diluted in the commercial extender EquiPro™ (Minitüb GmbH, Tiefenbach, Germany). After each set-up storage period, the motile fraction of sperm cells was selected by the swim-up method. The X/Y ratio was evaluated by fluorescence in situ hybridization (FISH) in the fresh, non-selected sperm, and in motile spermatozoa selected after each of the storage periods. Molecular probes for the equine chromosomes X and Y were used. The X/Y ratio in all sperm samples analysed in this study (fresh and stored) was not different from the theoretical 1 : 1 value. The incidence of chromosomally abnormal sperm cells in the fresh (0.28%) and motile (0.13%) sperm samples was not significantly different. The two approaches (sperm storage up to 48 h and the swim-up procedure) applied to this study did not affect the X/Y ratio in the motile fraction of equine spermatozoa. This finding does not conform to phenomena described for human and cattle. For this reason, the finding may imply species-related differences.

Genetic analysis of milk urea nitrogen and relationships with yield and fertility across lactation.

The aim of this project was to investigate the relationship of milk urea nitrogen (MUN) with 3 milk production traits [milk yield (MY), fat yield (FY), protein yield (PY)] and 6 fertility measures (number of inseminations, calving interval, interval from calving to first insemination, interval from calving to last insemination, interval from first to last insemination, and pregnancy at first insemination). Data consisted of 635,289 test-day records of MY, FY, PY, and MUN on 76,959 first-lactation Swedish Holstein cows calving from 2001 to 2003, and corresponding lactation records for the fertility traits. Yields and MUN were analyzed with a random regression model followed by a multi-trait model in which the lactation was broken into 10 monthly periods. Heritability for MUN was stable across lactation (between 0.16 and 0.18), whereas MY, FY, and PY had low heritability at the beginning of lactation, which increased with time and stabilized after 100 d in milk, at 0.47, 0.36, and 0.44, respectively. Fertility traits had low heritabilities (0.02 to 0.05). Phenotypic correlations of MUN and milk production traits were between 0.13 (beginning of lactation) and 0.00 (end of lactation). Genetic correlations of MUN and MY, FY, and PY followed similar trends and were positive (0.22) at the beginning and negative (-0.15) at the end of lactation. Phenotypic correlations of MUN and fertility were close to zero. A surprising result was that genetic correlations of MUN and fertility traits suggest a positive relationship between the 2 traits for most of the lactation, indicating that animals with breeding values for increased MUN also had breeding values for improved fertility. This result was obtained with a random regression model as well as with a multi-trait model. The analyzed group of cows had a moderate level of MUN concentration. In such a population MUN concentration may increase slightly due to selection for improved fertility. Conversely, selection for increased MUN concentration may improve fertility slightly.

Inbreeding rate and genetic structure of cat populations in Poland.

The objective of the study was to analyze effective population size and inbreeding level in populations of cat breeds registered in the Polish Studbook. The Association of Purebred Cat Breeders in Poland provided access to pedigrees of 26725 cats from seven breeds. The most frequent breed was Persian, however increasing tendency in numbers of registered animals from other breeds was recorded in later years. Although the percentage of inbred individuals was increasing over time, mating of close relatives was avoided by most of the breeders, and the average inbreeding coefficient exceeded 5% only for Siberian and Russian breeds. Current analysis suggests that the Polish pedigree cat populations are not threatened by negative effects of inbreeding.

Effects of incomplete pedigree on genetic management of the Dutch Landrace goat.

Genetic diversity in the Dutch Landrace goat was investigated based on information from the pedigree with about 6500 animals. Annual inbreeding rate after 1985 was below 0.5% and after 1987 close to 0%. However, pedigree information was incomplete, and 350 animals had unknown parents, while for the majority the real parents must have been in the pedigree. To determine the influence of unknown parents, 20 new pedigrees were created by random assignment of animals, alive at the time of birth, as parents to individuals with unknown parents. Only 12 founders remained for these pedigrees, and inbreeding levels varied considerably between these 20 pedigrees. However, inbreeding rates were remarkably constant. They increased to about 0.2%, indicating that the population is not endangered by inbreeding. The optimal contribution theory was used to evaluate possibilities of decreasing the average relationship in the population and thus to increase the genetic diversity of the breed. Optimal contribution decreased the average relationship in the population whether randomly assigned parents were used or not. However, individuals selected as parents for the resampled pedigrees differed from the original pedigree, and only a few animals were selected for all pedigrees. Candidates for inclusion in the genebank were also selected using optimal contribution. Adding animals to the genebank increased the conserved genetic diversity substantially, but as the lists differed between the analysed pedigrees it was not clear which animals were best added to the genebank.

JNK inhibition sensitises hepatocellular carcinoma cells but not normal hepatocytes to the TNF-related apoptosis-inducing ligand.

BACKGROUND: cJun terminal kinase (JNK) is constitutively activated in most hepatocellular carcinomas (HCCs), yet its exact role in carcinogenesis remains controversial. While tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a major mediator of acquired immune tumour surveillance, and is currently being tested in clinical trials as a novel cancer therapy, the resistance of many tumours to TRAIL and concerns about its toxicity in vivo represent obstacles to its clinical application. In this study we investigated whether JNK activity in HCC could contribute to the resistance to apoptosis in these tumours. METHODS: The effect of JNK/Jun inhibition on receptor-mediated apoptosis was analysed by pharmacological inhibition or RNA interference in cancer cells and non-tumour cells isolated from human liver or transgenic mice lacking a phosphorylation site for Jun. RESULTS: JNK inhibition caused cell cycle arrest, enhanced caspase recruitment, and greatly sensitised HCC cells but not normal hepatocytes to TRAIL. TRAIL-induced activation of JNK could be effectively interrupted by administration of the JNK inhibitor SP600125. CONCLUSIONS: Expression and TRAIL-dependent feedback activation of JNK likely represent a mechanism by which cancer cells escape TRAIL-mediated tumour surveillance. JNK inhibition might represent a novel strategy for specifically sensitising HCC cells to TRAIL thus opening promising therapeutic perspectives for safe and effective use of TRAIL in cancer treatment.