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51.
Mahdi Saatchi Mathew C McClure Stephanie D McKay Megan M Rolf JaeWoo Kim Jared E Decker Tasia M Taxis Richard H Chapple Holly R Ramey Sally L Northcutt Stewart Bauck Brent Woodward Jack CM Dekkers Rohan L Fernando Robert D Schnabel Dorian J Garrick Jeremy F Taylor 《遗传、选种与进化》2011,43(1):40
Background
Genomic selection is a recently developed technology that is beginning to revolutionize animal breeding. The objective of this study was to estimate marker effects to derive prediction equations for direct genomic values for 16 routinely recorded traits of American Angus beef cattle and quantify corresponding accuracies of prediction.Methods
Deregressed estimated breeding values were used as observations in a weighted analysis to derive direct genomic values for 3570 sires genotyped using the Illumina BovineSNP50 BeadChip. These bulls were clustered into five groups using K-means clustering on pedigree estimates of additive genetic relationships between animals, with the aim of increasing within-group and decreasing between-group relationships. All five combinations of four groups were used for model training, with cross-validation performed in the group not used in training. Bivariate animal models were used for each trait to estimate the genetic correlation between deregressed estimated breeding values and direct genomic values.Results
Accuracies of direct genomic values ranged from 0.22 to 0.69 for the studied traits, with an average of 0.44. Predictions were more accurate when animals within the validation group were more closely related to animals in the training set. When training and validation sets were formed by random allocation, the accuracies of direct genomic values ranged from 0.38 to 0.85, with an average of 0.65, reflecting the greater relationship between animals in training and validation. The accuracies of direct genomic values obtained from training on older animals and validating in younger animals were intermediate to the accuracies obtained from K-means clustering and random clustering for most traits. The genetic correlation between deregressed estimated breeding values and direct genomic values ranged from 0.15 to 0.80 for the traits studied.Conclusions
These results suggest that genomic estimates of genetic merit can be produced in beef cattle at a young age but the recurrent inclusion of genotyped sires in retraining analyses will be necessary to routinely produce for the industry the direct genomic values with the highest accuracy. 相似文献52.
Microsatellite variation in Drosophila melanogaster and Drosophila simulans: a reciprocal test of the ascertainment bias hypothesis 总被引:1,自引:1,他引:1
Interspecific comparisons of microsatellite loci have repeatedly shown that
the loci are longer and more variable in the species from which they are
derived (the focal species) than are homologous loci in other (nonfocal)
species. There is debate as to whether this is due to directional evolution
or to an ascertainment bias during the cloning and locus selection
processes. This study tests these hypotheses by performing a reciprocal
study. Eighteen perfect dinucleotide microsatellite loci identified from a
Drosophila simulans library screen and 18 previously identified in an
identical Drosophila melanogaster library screen were used to survey
natural populations of each species. No difference between focal and
nonfocal species was observed for mean PCR fragment length. However,
heterozygosity and number of alleles were significantly higher in the focal
species than in the nonfocal species. The most common allele in the
Zimbabwe population of both species was sequenced for 31 of the 36 loci.
The length of the longest stretch of perfect repeat units is, on average,
longer in the focal species than in the non-focal species. There is a
positive correlation between the length of the longest stretch of perfect
repeats and heterozygosity. The difference in heterozygosity can thus be
explained by a reduction in the length of the longest stretch of perfect
repeats in the nonfocal species. Furthermore, flanking-sequence length
difference was noted between the two species at 58% of the loci sequenced.
These data do not support the predictions of the directional-evolution
hypothesis; however, consistent with the ascertainment bias hypothesis, the
lower variability in nonfocal species is an artifact of the microsatellite
cloning and isolation process. Our results also suggest that the magnitude
of ascertainment bias for repeat unit length is a function of the
microsatellite size distribution in the genomes of different species.
相似文献
53.
Caitlyn E Abell Jack CM Dekkers Max F Rothschild John W Mabry Kenneth J Stalder 《遗传、选种与进化》2014,46(1):32
Background
Determining an animal’s genetic merit using genomic information can improve estimated breeding value (EBV) accuracy; however, the magnitude of the accuracy improvement must be large enough to recover the costs associated with implementing genome-enabled selection. One way to reduce costs is to genotype nucleus herd selection candidates using a low-density chip and to use high-density chip genotyping for animals that are used as parents in the nucleus breeding herd. The objective of this study was to develop a tool to estimate the cost structure associated with incorporating genome-enabled selection into multi-level commercial breeding programs.Results
For the purpose of this deterministic study, it was assumed that a commercial pig is created from a terminal line sire and a dam that is a cross between two maternal lines. It was also assumed that all male and female selection candidates from the 1000 sow maternal line nucleus herds were genotyped at low density and all animals used for breeding at high density. With the assumptions used in this analysis, it was estimated that genome-enabled selection costs for a maternal line would be approximately US$0.082 per weaned pig in the commercial production system. A total of US$0.164 per weaned pig is needed to incorporate genome-enabled selection into the two maternal lines. Similarly, for a 600 sow terminal line nucleus herd and genotyping only male selection candidates with the low-density panel, the cost per weaned pig in the commercial herd was estimated to be US$0.044. This means that US$0.21 per weaned pig produced at the commercial level and sired by boars obtained from the nucleus herd breeding program needs to be added to the genetic merit value in order to break even on the additional cost required when genome-enabled selection is used in both maternal lines and the terminal line.Conclusions
By modifying the input values, such as herd size and genotyping strategy, a flexible spreadsheet tool developed from this work can be used to estimate the additional costs associated with genome-enabled selection. This tool will aid breeders in estimating the economic viability of incorporating genome-enabled selection into their specific breeding program. 相似文献54.
CM Ward AP Wilkinson S Bramham HA Lee HW-S Chan GW Butcher A Hutchings MRA Morgan 《Mycotoxin Research》1990,6(2):73-83
From a single aflatoxin B1 oxime — bovine serum albumin conjugate, polyclonal and monoclonal antibody preparations were produced. The four rabbit polyclonal antisera were specific for aflatoxin Bi in a microtitration plate enzyme — linked immunosorbent assay. The monoclonal antibodies showed a wide range of differing specificities, recognizing, for example, aflatoxins B1, B2, G1 and G2; B1 and B2; B1 and G1; and G1 alone. No antibody preparations reacted with aflatoxin M1. The significance of these results to the strategy of anti-aflatoxin antibody production for use in quantitative enzyme immunoassays is discussed. 相似文献
55.
Tom?PMM?VluggenEmail author Jolanda?CM?van Haastregt Jeanine?A?Verbunt Elly?JM?Keijsers Jos?MGA?Schols 《BMC neurology》2012,12(1):164
Background
Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients.Methods
A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge.Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014.Trial registration
International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR241256.
57.
58.
Liviu R Totir Rohan L Fernando Jack CM Dekkers Soledad A Fernández Bernt Guldbrandtsen 《遗传、选种与进化》2004,36(1):29-48
Under additive inheritance, the Henderson mixed model equations (HMME) provide an efficient approach to obtaining genetic evaluations by marker assisted best linear unbiased prediction (MABLUP) given pedigree relationships, trait and marker data. For large pedigrees with many missing markers, however, it is not feasible to calculate the exact gametic variance covariance matrix required to construct HMME. The objective of this study was to investigate the consequences of using approximate gametic variance covariance matrices on response to selection by MABLUP. Two methods were used to generate approximate variance covariance matrices. The first method (Method A) completely discards the marker information for individuals with an unknown linkage phase between two flanking markers. The second method (Method B) makes use of the marker information at only the most polymorphic marker locus for individuals with an unknown linkage phase. Data sets were simulated with and without missing marker data for flanking markers with 2, 4, 6, 8 or 12 alleles. Several missing marker data patterns were considered. The genetic variability explained by marked quantitative trait loci (MQTL) was modeled with one or two MQTL of equal effect. Response to selection by MABLUP using Method A or Method B were compared with that obtained by MABLUP using the exact genetic variance covariance matrix, which was estimated using 15 000 samples from the conditional distribution of genotypic values given the observed marker data. For the simulated conditions, the superiority of MABLUP over BLUP based only on pedigree relationships and trait data varied between 0.1% and 13.5% for Method A, between 1.7% and 23.8% for Method B, and between 7.6% and 28.9% for the exact method. The relative performance of the methods under investigation was not affected by the number of MQTL in the model. 相似文献
59.
Christof J Majoor Marianne A van de Pol Pieter Willem Kamphuisen Joost CM Meijers Richard Molenkamp Katja C Wolthers Tom van der Poll Rienk Nieuwland Sebastian L Johnston Peter J Sterk Elisabeth HD Bel Rene Lutter Koenraad F van der Sluijs 《Respiratory research》2014,15(1):14
Background
Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.Methods
28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation).Results
13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1.Conclusions
Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.Trial registration
This trial was registered at the Dutch trial registry (http://www.trialregister.nl): NTR1677. 相似文献60.
Teng YK Verburg RJ Verpoort KN Diepenhorst GM Bajema IM van Tol MJ Jol-van der Zijde EC Toes RE Huizinga TW van Laar JM 《Arthritis research & therapy》2007,9(5):R106
In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated
protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy
(HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized
in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against
rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was
measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial
biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with
clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy
were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median
of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to
388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were
differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies
as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative
therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity. 相似文献