A comparison of several methodologies of selection index for productive and reproductive characteristics in Egyptian buffaloes.

Data on Egyptian buffalo first lactation records (n = 1167) available at Mehalet Mousa Farm (between 2002 and 2015) of the Animal Production Research Institute (APRI), Cairo, Egypt, were used to analyse the genetic parameters of total milk yield (TMY), lactation time (LP), and age at first calving (AFC). Additionally, four selection indices were created by using a single phenotypic standard derivation as relevant economic values. The data were evaluated using multiple-trait derivative-free restricted maximum likelihood (MTDFREML). The estimated heritabilities for TMY, LP, and AFC were 0.22, 0.17, and 0.08 respectively and the phenotypic and genetic correlations between TMY and LP were 0.76 and 0.56, respectively, and between AFC with TMY and LP were nеgаtivеs. Using a selection index that incorporates TMY, LP, and AFC (RIH = 0.68) looks to be optimum for increased genetic gain and a shorter generation interval; as a result, selection should thus be exercised near the end of the first lactation.

Contribution of social genetic effects in variance components estimation for body weight in Nigerian indigenous chickens raised in a tropical humid location.

Social interactions among chickens can have a great unfavourable effect on economic returns in a poultry farm. The purpose of this study was to use four models to examine the influence of social genetic influences on the variation in body weight of Nigerian indigenous chickens. Sex was treated as the fixed effect within the models. Direct additive genetic, social genetic, and family effects and covariance between direct and social genetic effects were used as random effects. Data were analysed using single-trait animal models which include or exclude social genetic effects. Model comparison revealed that inclusion of full-sib family effect in model 3 did not cause any change in residual and additive genetic variances relative to estimates obtained with model 2. In general, social genetic variance was lower than the estimate for additive genetic variance, but substantially added to the overall heritable variance. For direct hereditary, full-sib family, and residual effects, accounting for heritable social effect in model 4 had a marginal effect on the size of the variances measured. All the estimated residual, additive genetic, social genetic effect, and family variances increased in comparison with model 3. The relationship between direct and social additive effects was positive and not significantly different from 0 (P > 0.05), suggesting autonomy between the direct and social breeding values. In conclusion, the use of models that account for direct effect and social genetic effect of the individual on its group members would entail an optimal individual selection scheme to increase the body weight of chickens.

Use of discriminant analysis for the evaluation of coccidiosis resistance parameters in chickens raised in hot humid tropical environment.

Coccidiosis endemicity remains a major challenge in poultry production in the tropics and all over the world. In order to develop predictive tool for identification of chickens that are at risk of coccidiosis among Nigerian indigenous chickens, body weight gain (BWG) and hematological variables were determined for chickens infected with Eimeria tenella (female = 60, male = 63) and uninfected (female = 51, male = 45). The hematological variables analyzed include the following: packed cell volume (PCV, %), white blood cells (WBC, × 106/µl), and red blood cells (RBC, × 106/µl), as well as differential leucocyte percentages of neutrophils, lymphocytes, monocytes, and eosinophils. Body weight gain was determined at days 3, 6, 9, 12, and 15. Of the 12 variables analyzed, BWG at day 3, monocyte, PCV, and WBC in males and BWG at days 6, 9, and 12, PCV, and WBC in female chickens showed significant (P ≤ 0.01) difference between the infected and uninfected. Stepwise discriminant analysis evolved a model that could distinguish uninfected from Eimeria-infected chickens. Packed cell volume, WBC, BWG at day 3, and lymphocytes emerged the most discriminant between uninfected and Eimeria-infected chickens in male chickens. In female chickens, PCV, RBC, and BWG at day 3 were identified as most discriminant variables in separating the uninfected from Eimeria-infected chickens. Therefore, this study suggests that routine blood test and estimates of body weight gain could serve as a useful tool for identifying chickens that may be at risk of coccidiosis, enabling improvement of preventive measures.

Use of robust multivariate linear mixed models for estimation of genetic parameters for carcass traits in beef cattle.

Assumptions of normality of residuals for carcass evaluation may make inferences vulnerable to the presence of outliers, but heavy-tail densities are viable alternatives to normal distributions and provide robustness against unusual or outlying observations when used to model the densities of residual effects. We compare estimates of genetic parameters by fitting multivariate Normal (MN) or heavy-tail distributions (multivariate Student's t and multivariate Slash, MSt and MS) for residuals in data of hot carcass weight (HCW), longissimus muscle area (REA) and 12th to 13th rib fat (FAT) traits in beef cattle using 2475 records from 2007 to 2008 from a large commercial operation in Nebraska. Model comparisons using deviance information criteria (DIC) favoured MSt over MS and MN models, respectively. The posterior means (and 95% posterior probability intervals, PPI) of v for the MSt and MS models were 5.89 ± 0.90 (4.35, 7.86) and 2.04 ± 0.18 (1.70, 2.41), respectively. Smaller values of posterior densities of v for MSt and MS models confirm that the assumption of normally distributed residuals is not adequate for the analysis of the data set. Posterior mean (PM) and posterior median (PD) estimates of direct genetic variances were variable with MSt having the highest mean value followed by MS and MN, respectively. Posterior inferences on genetic variance were, however, comparable among the models for FAT. Posterior inference on additive heritabilities for HCW, REA and FAT using MN, MSt and MS models indicated similar and moderate heritability comparable with the literature. Posterior means of genetic correlations for carcass traits were variable but positive except for between REA and FAT, which showed an antagonistic relationship. We have demonstrated that genetic evaluation and selection strategies will be sensitive to the assumed model for residuals.

Effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of turkeys, hatchability of eggs and post-hatch growth of their offsprings.

The effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of breeder turkeys, hatchability of eggs and post-hatch growth response was investigated using 180 breeder hens. The hens were assigned to six dietary treatments in a 2 × 3 factorial arrangements of two application modes of L-carnitine (diet and drinking water) supplemented at 0, 50 and 100 ppm (mg/kg or mg/l) levels, respectively. Each treatment was replicated five times with six hens per replicate. Dietary inclusion of 50 ppm L-carnitine showed the lowest (p < 0.01) plasma total cholesterol (TC) and low-density lipoprotein concentration (LDL). Breeder hens offered 50 ppm L-carnitine with no regard to application mode recorded the highest (p < 0.01) plasma high-density lipoprotein (HDL). Hens offered 50 and 100 ppm L-carnitine irrespective of application mode also showed reduced (p < 0.01) egg-yolk TC concentration at 32 weeks of age. Dietary supplementation of 50 ppm L-carnitine for breeder turkeys recorded the lowest (p < 0.01) egg-yolk triglyceride (TG) at 40 weeks of age. Hens offered 50 ppm L-carnitine irrespective of application mode recorded the highest (p < 0.05) hen-day egg production. Incidence of dead-in-shell also reduced (p < 0.05) with increasing dosage of L-carnitine. Dietary supplementation of 50 ppm and oral application in drinking water of 100 ppm L-carnitine for breeder turkeys resulted in highest (p < 0.05) egg fertility. Offsprings from breeder hens fed diets supplemented with L-carnitine recorded no post-hatch mortality. Highest (p < 0.05) post-hatch final live weight and weight gain was obtained with poults obtained from hens fed diet supplemented with 50 ppm L-carnitine. In conclusion, dietary supplementation of 50 ppm L-carnitine for turkey hens showed improved serum lipid profile, egg fertility, reduced dead-in-shell, egg-yolk cholesterol and resulted in improved post-hatch growth performance.

Equine maternal aging affects the metabolomic profile of oocytes and follicular cells during different maturation time points.

Introduction: Oocyte quality and fertility decline with advanced maternal age. During maturation within the ovarian follicle, the oocyte relies on the associated somatic cells, specifically cumulus and granulosa cells, to acquire essential components for developmental capacity. Methods: A nontargeted metabolomics approach was used to investigate the effects of mare age on different cell types within the dominant, follicular-phase follicle at three time points during maturation. Metabolomic analyses from single oocytes and associated cumulus and granulosa cells allowed correlations of metabolite abundance among cell types. Results and Discussion: Overall, many of the age-related changes in metabolite abundance point to Impaired mitochondrial metabolic function and oxidative stress in oocytes and follicular cells. Supporting findings include a higher abundance of glutamic acid and triglycerides and lower abundance of ceramides in oocytes and somatic follicular cells from old than young mares. Lower abundance of alanine in all follicular cell types from old mares, suggests limited anaerobic energy metabolism. The results also indicate impaired transfer of carbohydrate and free fatty acid substrates from cumulus cells to the oocytes of old mares, potentially related to disruption of transzonal projections between the cell types. The identification of age-associated alterations in the abundance of specific metabolites and their correlations among cells contribute to our understanding of follicular dysfunction with maternal aging.

Maturation and culture affect the metabolomic profile of oocytes and follicular cells in young and old mares.

Introduction: Oocytes and follicular somatic cells within the ovarian follicle are altered during maturation and after exposure to culture in vitro. In the present study, we used a nontargeted metabolomics approach to assess changes in oocytes, cumulus cells, and granulosa cells from dominant, follicular-phase follicles in young and old mares. Methods: Samples were collected at three stages associated with oocyte maturation: (1) GV, germinal vesicle stage, prior to the induction of follicle/oocyte maturation in vivo; (2) MI, metaphase I, maturing, collected 24 h after induction of maturation in vivo; and (3) MIIC, metaphase II, mature with collection 24 h after induction of maturation in vivo plus 18 h of culture in vitro. Samples were analyzed using gas and liquid chromatography coupled to mass spectrometry only when all three stages of a specific cell type were obtained from the same mare. Results and Discussion: Significant differences in metabolite abundance were most often associated with MIIC, with some of the differences appearing to be linked to the final stage of maturation and others to exposure to culture medium. While differences occurred for many metabolite groups, some of the most notable were detected for energy and lipid metabolism and amino acid abundance. The study demonstrated that metabolomics has potential to aid in optimizing culture methods and evaluating cell culture additives to support differences in COCs associated with maternal factors.

Genetic evaluation of semen traits in Friesian bulls raised in Egypt.

A total of 14696 semen records were collected from Friesian bulls, kept at International Livestock Management Training Center belonging to Animal Research Institute, Ministry of Agriculture, Dokki, Cairo. Traits studied were volume, motility, livability and sperm concentrates in other to construct selection indexes by using all combination between different traits of semen to improve semen traits in a herd of Friesian bull cattle. Data were analysed by using four traits repeatability model and includes effects of the following fixed factors: the age of animal at semen collection, the combined effect of the month and year of semen collection, and the number of times semen were collected per month. Semen motility, volume and livability were highly influenced (p < 0.001) by all the fixed factors. Heritability estimates for semen traits were moderate and ranged from 0.29 to 0.33. All phenotypic and genetic correlations between different traits are positive and ranged from 0.09 to 0.67 for phenotypic correlations and from 0.02 to 0.68 for genetic correlations, while permanent environmental correlations ranged from -0.69 to 0.12. Estimated Breeding Values ranged from -0.68 to 0.78 ml for semen volume, from -13.17 to 7.34% for motility, from -259.42 × 10-6 to 239.64 × 10-6 for concentrates and from -6.83 to 6.09% for livability. Eleven selection indexes were calculated, selection Indexes not including livability showed a reduced accuracy. This study demonstrated that selection index (I3) which includes sperm volume, motility and livability or selection index (I8) which includes sperm volume and livability are the best and both are recommended for Friesian bulls' selection.

Growth performance of Nigerian local chickens in crosses involving an exotic broiler breeder.

Six-hundred-and-seven-day-old chicks were generated from Nigerian local chickens consisting of three genotypes (Normal-feathered; Frizzled-feathered; Naked neck) and an exotic broiler breeder (Anak Titan) to evaluate growth performance for possible meat-type chicken development. Growth parameters measured were body weight, breast girth and keel length on weekly basis for 20 weeks. Effects of sire, dam and chick genotypes were significant (P<0.001) on growth traits. At week 20, chickens sired by the Anak Titan weighed 1,614.82 g followed by Normal-feathered local chickens with body weight of 1,211.32 g. Progenies of Anak Titan and Naked neck dams weighed 1,761.96 and 1,292.80 g at week 20, respectively. Among purebreds, Anak Titan weighed 35.05 g at day-old and had heaviest body weight of 2,360.29 g at 20 weeks compared to the three local strains. The average body weights for the crossbred, Normal-feathered × Anak Titan at day-old and week 20 were 36.39 and 1,577.63 g, respectively. This was followed by Anak Titan × Naked neck with 33.32 g at day-old and 1,514.14 g at week 20. Sex had significant effect (P<0.05) at weeks 16 and 20 with the males having higher mean values than their female counterparts. This study revealed that crosses involving Anak Titan sire × Naked neck dam had highest growth performance, and there was no strain differences among the growth performance of purebred Nigerian local chickens.

The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit.

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2-4-h intervals of culture over 24-48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2-4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting.

Metronomic trofosfamide inhibits progression of human lung cancer xenografts by exerting anti-angiogenic effects.

BACKGROUND: Recent studies of conventional chemotherapeutic drugs administered in metronomic therapy schedules showed remarkable inhibitory effects on tumor angiogenesis. Subsequent and prolonged tumor regression was achieved moreover by circumventing acquired drug resistance. In this study, metronomic and conventional trofosfamide were compared on human NSCLC xenograft "LX-1." MATERIALS AND METHODS: In vitro cytotoxicity of trofosfamide on tumor and human umbilical cord endothelial cells was determined under normoxic and hypoxic conditions. Additionally fractions and duration of cell cycles were analyzed by flow cytometry. In vivo LX-1 xenotransplanted nude mice were treated with trofosfamide in conventional and metronomic schedules (i.p./p.o.). Tumor sections were evaluated for microvessel density (MVD), relative growth fraction and apoptosis. RESULTS: In contrast to the rapid growth of conventionally treated lung cancer, long lasting tumor growth retardation over the total treatment period was achieved with metronomic treatment. While growth fraction and apoptotic rate of LX-1 cells remained unchanged, the MVD was significantly reduced (50%). CONCLUSION: Our results show advantages of a metronomic trofosfamide schedule compared to a conventional bolus therapy mainly due to inhibition of angiogenesis. In vitro data show that this mechanism works under normoxic and hypoxic conditions and suggest that this is in part a direct cytotoxic effect on endothelial cells.

Murine marrow cells expanded in culture with IL-3, IL-6, IL-11, and SCF acquire an engraftment defect in normal hosts.

Stimulatory cytokines may induce murine hematopoietic progenitor cells (HPCs) to survive, self-renew, proliferate, or differentiate. We studied the role of active cell cycling induced by the cytokines interleukin-3 (IL-3), IL-6, IL-11, and Steel factor (SF) on murine progenitor cell frequency and cell cycle status in an in vitro system and on engraftment potential in nonmyeloablated mice. Marrow exposure to IL-3, IL-6, IL-11, and SF in in vitro liquid culture maintained or expanded seven factor-responsive high and low proliferative potential colony-forming cells (HPP-CFC and LPP-CFC). The HPP-CFC and LPP-CFC were dormant at the initiation of culture, as determined by 3H-thymidine suicide. There was an increase in the number and proliferation of HPP-CFC and LPP-CFC at 48 hours; by 48 hours, 62% of HPP-CFC and 56% of LPP-CFC were killed by 3H-TdR exposure. In engraftment studies of cytokine-stimulated marrow cells into normal hosts, female BALB/c mice received the equivalent of 40 x 10(6) starting male marrow cells exposed to cytokines in vitro for 48 hours for 3 consecutive days and were sacrificed 8 weeks after transplantation. Control groups received either 40 x 10(6) male uncultured marrow cells, 40 x 10(6) starting marrow cells cultured in medium without growth factors for 48 hours, or phosphate-buffered saline (PBS) for 3 days. Engraftment of male cytokine-treated cells was analyzed by Southern blot analysis using the Y-chromosome-specific pY2-cDNA probe. There was minimal engraftment (approaching background levels) in marrow, spleen, and thymus of nonmyeloablated female recipients. Transplant recipients that had received uncultured marrow directly after sacrifice showed engraftment levels of 21% (11 mice; range = 8 to 44%) into marrow, of 9% (range = 0 to 22%) into spleen, and 13% (range = 2 to 43%) into thymus. We conclude that active cell cycling of marrow cells induced by cytokine stimulation is associated with an engraftment defect in the normal host.

Increasing the yield of harvested bone marrow cells by raising room temperature during marrow collection.

The time it takes to harvest bone marrow before transplantation could be reduced significantly by increasing the temperature of the operating room by 8-10 degrees C, to about 28-30 degrees C. In healthy donors, the collected volume of marrow was increased from 22.45 to 36.31 mL/min; in patients who received chemotherapy previously, from 21.67 to 29.98 mL/min. The time to collect a volume of 1200 mL marrow could be reduced significantly, from 57.78 to 38.25 minutes in healthy donors and from 71.07 to 43.36 minutes in patients who received chemotherapy previously, without any loss of quality of the sampled marrow. Operation time and thereby time of anesthesia could be reduced significantly by heating the operating room to a temperature of 28-30 degrees C. Harvesting at higher room temperature did not result in any adverse side effects for the patients. The procedure to increase the body temperature could be simplified by using electric blankets and aluminum foils for wrapping to avoid heat emission.

Stem cell transplantation in the normal nonmyeloablated host: relationship between cell dose, schedule, and engraftment.

In previous studies we have shown high rates of stable engraftment when 40 million male BALB/c cells were infused intravenously daily for 5 days (a total of 200 million cells) to normal nonmyeloablated female hosts. The present studies evaluate engraftment of male BALB/c bone marrow cells in female host marrow, spleen, and thymus 20-25 weeks after transplantation using varying cell dosages within a 5-day schedule. Engraftment in recipient mice was assessed by detection of male specific sequence in recipient DNA from each organ. When 40 million cells were given per daily injection for 1, 2, 3, 4, or 5 days, engraftment percentages in host marrow were 11 +/- 0.83, 20 +/- 2.0, 23 +/- 2.5, 32 +/- 6.3, and 39% +/- 5.7 (+/- standard error of mean), respectively, yielding engraftment percentages per million cells infused of 0.28, 0.25, 0.19, 0.20, and 0.20%, respectively. When levels of 2.5, 5, 10, 20, or 40 million cells were injected 5 times over a 5-day schedule into normal BALB/c female hosts, progressively increasing levels of engraftment from 3 +/- 0.6 to 39% +/- 5.7 were seen in host marrow. Highest levels of engraftment per million cells injected were obtained on days 1 and 2 of a 5-day schedule and with a level of 10 million cells given daily over 5 days. Engraftment profiles varied with spleen and thymus and percent engraftment was generally lower than for marrow. The present work indicates that regardless of cell level infused or number of infusions, rates of engraftment observed in marrow approached or exceeded the highest rates of engraftment estimated by theoretical calculations based on replacing host cells ("replacement model") or adding to host cells ("incremental model"). Engraftment in spleen and thymus was lower, but also at times approached or exceeded theoretical maxima. These data show extraordinary levels of engraftment in normal hosts, suggesting that rates in this competitive model are superior to those seen in irradiated hosts; alternatively, there may be selective repression of host stem cell proliferation and differentiation.

A preclinical model for experimental chemotherapy of human head and neck cancer.

We developed a mouse model in a representative human derived head and neck cancer cell line for preclinical studies to evaluate antitumor response, tumor-free survival and host toxicity of alkylating agents, antimetabolites, platinum analogs and taxanes alone or in combination. Ninety athymic NMRI mice were inoculated with human derived oral squamous cell carcinoma cells growing on the hind paw to an average volume of 180 +/- 80 mm3. Animals were stratified according to tumor volume into 10 groups (n=6-10) and treated with ifosfamide (65 mg/kg b.w.), docetaxel (24 mg/kg b.w.), cisplatin (2 mg/kg b.w.), carboplatin (6 or 10 mg/kg b.w.), methotrexate (1 mg/kg b.w.), and fluorouracil (15 mg/kg b.w.) intravenously in single agent or combination (ifosfamide plus docetaxel or ifosfamide plus carboplatin) treatment schedules or controls. Tumor volume was measured 3 times per week for 60 days. The average tumor volume, the overall survival time and the response rates (CR, PR) of the treated animals were compared with the data obtained from untreated controls and statistically evaluated. Untreated tumors showed rapid and exponential tumor growth. Single agent therapies with ifosfamide, cisplatinum, and docetaxel lead to significant tumor regression and improved overall survival. Low dose carboplatin monotherapy induced significant tumor growth delay, but not significant tumor regression. Most impressive tumor-free survival was achieved by combination treatment with ifosfamide and docetaxel. This preclinical study demonstrates an animal model capable of differentiating various chemotherapy regimens.

Ifosfamide, carboplatin and etoposide combined with 41.8 degrees C whole body hyperthermia for malignant pleural mesothelioma.

We performed a phase II study combining 41.8 degrees C whole body hyperthermia with ICE chemotherapy, i.e. ifosfamide (5 g/m(2)), carboplatin (300 mg/m(2)) and etoposide (150 mg/m(2) on days 2 and 3), administered every 4 weeks, for patients with malignant pleural mesothelioma. Of 27 chemonäive, non-metastatic patients enrolled, 25 patients were evaluable for response. Overall response rate was 20% (five partial remissions; 95% CI 8.9-39.1%). Median survival time from the start of treatment for all patients was 76.6 weeks (95% CI 65.4-87.8 weeks). Progression free survival for all patients measured 29.6 weeks (95% CI 24.4-34.7 weeks). One year overall survival was 68% and 2 year overall survival was 20%. Major treatment toxicities included grade 3/4 neutropenia and thrombocytopenia in 74 and 33% of treatment cycles, respectively. One patient died due to sepsis. These promising results are consistent with continued clinical investigation; a phase III clinical trial with whole body hyperthermia as the independent variable has been initiated.

Infusion of tumor-contaminated bone marrow for autologous rescue after high-dose therapy leading to long-term remission in a patient with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report a female patient with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia remaining in long-term second remission after high-dose radiochemotherapy followed by autologous stem cell rescue with bone marrow showing evidence of residual disease. The Philadelphia chromosome and a positive signal for the BCR/ABL p185 translocation by the polymerase chain reaction were detected in the harvested marrow. After mafosfamide-purged marrow failed to engraft, her unpurged 'back-up' bone marrow was also infused. Control marrow examinations after recovery were repeatedly positive for the BCR/ABL translocation on PCR analysis turning negative 30 months after high-dose therapy. She remains in unsustained complete clinical remission for 48+ months showing no evidence of leukemia by cytological and cytogenetic analyses.

Effects of cytokines on stem cell engraftment depends on time of evaluation post-marrow-infusion.

In vitro treatment of bone marrow cells to expand stem cells may lead to impaired hematopoietic long-term reconstitution. Here we report on studies that show that cytokine-treated cells maintain short-term reconstitution, but lose that potential with time posttransplantation. Hematopoietic progenitors assayed in vitro as high- and low-proliferative potential colony-forming cells, when exposed to four cytokines (interleukin (IL)-3, IL-6, IL-11, and stem cell factor) were significantly expanded and induced to enter the cell cycle. A competitive transplant model--which uses BALB/c mice of opposite genders: cytokine-treated male BALB/c marrow cells competed with fresh, noncultured female cells--gave mean engraftment levels of 47 +/- 3% at 1 week posttransplantation, 49 +/- 6% at 3 weeks, 30 +/- 10% at 6 weeks, 26 +/- 9% at 12 weeks, and 15 +/- 3% at 24 weeks. These data were confirmed using a congenic Ly 5.1/5.2 transplant model and suggest either that cytokines act differentially on separate sets of short-term and long-term repopulating cells or act on one population of stem cells to limit long-term repopulation.

Application of multivariate heavy-tailed distributions to residuals in the estimation of genetic parameters of growth traits in beef cattle.

Assumptions of normality in most animal breeding applications may make inferences vulnerable to the presence of outliers. Heavy-tail densities are viable alternatives to normal distributions and provide robustness against unusual or outlying observations when used to model the densities of residual effects. Our objective is to compare estimates of genetic parameters by fitting multivariate normal (MN) or heavy-tail distributions [multivariate Student's t (MSt) and multivariate slash (MS)] for residuals in data of body birth weight (BBW), weaning (WW), and yearling (YW) weight traits in beef cattle. A total of 17,019 weight records for BBW, WW, and YW from 1998 through 2010 from a large commercial cow/calf operation in the sand hills of Nebraska were analyzed. Models included fixed effects of contemporary group and sire breed whereas animal and maternal effects were random and the degrees of freedom (v) was treated as unknown for MSt and MS. Model comparisons using deviance information criteria (DIC) favored MSt over MS and MN models, respectively. The posterior means [and 95% posterior probability intervals (PPI)] of v for the MSt and MS models were 5.28 (4.80, 5.85) and 1.88 (1.76, 2.00), respectively. Smaller values of posterior densities of v for MSt and MS models confirm that the assumption of normally distributed residuals is not adequate for the analysis of BBW, WW, and YW datasets. Posterior mean (PM) and posterior median (PD) estimates of direct and maternal genetic variances were the same and posterior densities of these parameters were found to be symmetric. The 95% PPI estimates from MN and MSt models for BBW did not overlap, which indicates significant difference between PM estimates from MN or MSt models. The observed antagonistic relationship between additive direct and additive maternal effects indicated that genetic evaluation and selection strategies will be sensitive to the assumed model for residuals.

Heritability and Bayesian genome-wide association study of first service conception and pregnancy in Brangus heifers.

Brangus [3/8 Brahman (Bos indicus) × 5/8 Angus (Bos taurus); n ≈ 800] heifers from 67 sires were used to estimate heritability and conduct a genome-wide association study (GWAS) for 2 binary fertility traits: first service conception (FSC) and heifer pregnancy (HPG). Genotypes were from 53,692 loci on the BovineSNP50 (Infinium Bead Chips, Illumina, San Diego, CA). Yearling heifers were estrous synchronized, bred by AI, and then exposed to natural service breeding. Reproductive ultrasound and DNA-based parentage testing were used to determine if the heifer conceived by AI or natural service, and code for FSC and HPG traits. Success rates for FSC and HPG were 53.3% and 78.0% ± 0.01%, and corresponding heritability estimates were 0.18 ± 0.07 and 0.10 ± 0.06, respectively. The models used in obtaining these heritability estimates and GWAS included fixed effects of year (i.e., 2005 to 2007), birth location, calving season, age of dam, and contemporary group. In GWAS, simultaneous associations of 1 Mb SNP windows with phenotype were undertaken with Bayes C analyses using GenSel software. The 1 Mb windows contained 21.3 ± 1.1 SNP. Analyses fitted a mixture model that treated SNP effects as random, with an assumed fraction pi = 0.9995 having no effect on phenotype. The windows that accounted for 1.0% of genetic variance were considered as QTL associated with FSC or HPG. Eighteen QTL existed on 15 chromosomes for the 2 traits. On average, each QTL accounted for 2.43% ± 0.2% of the genetic variance. Chromosome 8 harbored 2 QTL for FSC and 1 for HPG; however, these regions did not overlap. Chromosomes 3, 15, 16, 19, 24, 26, 27, 29, and X included QTL only for FSC, whereas chromosomes 2, 4, 10, 13, and 20 contained QTL only for HPG. The multitude of QTL detected for FSC and HPG in this GWAS involving Brangus heifers exemplifies the complex regulation of variation in heifer fertility traits of low heritability.