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31.
A strategy of multi-step minimal conditional regression analysis has been developed to determine the existence of statistical testing and parameter estimation for a quantitative trait locus (QTL) that are unaffected by linked QTLs. The estimation of marker-QTL recombination frequency needs to consider only three cases: 1) the chromosome has only one QTL, 2) one side of the target QTL has one or more QTLs, and 3) either side of the target QTL has one or more QTLs. Analytical formula was derived to estimate marker-QTL recombination frequency for each of the three cases. The formula involves two flanking markers for case 1), two flanking markers plus a conditional marker for case 2), and two flanking markers plus two conditional markers for case 3). Each QTL variance and effect, and the total QTL variance were also estimated using analytical formulae. Simulation data show that the formulae for estimating marker-QTL recombination frequency could be a useful statistical tool for fine QTL mapping. With 1 000 observations, a QTL could be mapped to a narrow chromosome region of 1.5 cM if no linked QTL is present, and to a 2.8 cM chromosome region if either side of the target QTL has at least one linked QTL. 相似文献
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M Teruel F J Ruíz-Ruano J A Marchal A Sánchez J Cabrero J PM Camacho F Perfectti 《Heredity》2014,112(5):531-542
Wide arrays of repetitive DNA sequences form an important part of eukaryotic genomes. These repeats appear to evolve as coherent families, where repeats within a family are more similar to each other than to other orthologous representatives in related species. The continuous homogenization of repeats, through selective and non-selective processes, is termed concerted evolution. Ascertaining the level of variation between repeats is crucial to determining which evolutionary model best explains the homogenization observed for these sequences. Here, for the grasshopper Eyprepocnemis plorans, we present the analysis of intragenomic diversity for two repetitive DNA sequences (a satellite DNA (satDNA) and the 45S rDNA) resulting from the independent microdissection of several chromosomes. Our results show different homogenization patterns for these two kinds of paralogous DNA sequences, with a high between-chromosome structure for rDNA but no structure at all for the satDNA. This difference is puzzling, considering the adjacent localization of the two repetitive DNAs on paracentromeric regions in most chromosomes. The disparate homogenization patterns detected for these two repetitive DNA sequences suggest that several processes participate in the concerted evolution in E. plorans, and that these mechanisms might not work as genome-wide processes but rather as sequence-specific ones. 相似文献
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Jacky Woo Michel PM Vierboom Hakju Kwon Debra Chao Shiming Ye Jianmin Li Karen Lin Irene Tang Nicole A Belmar Taymar Hartman Elia Breedveld Vladimir Vexler Bert A ‘t Hart Debbie A Law Gary C Starling 《Arthritis research & therapy》2013,15(6):R207
Introduction
Targeting the CD20 antigen has been a successful therapeutic intervention in the treatment of rheumatoid arthritis (RA). However, in some patients with an inadequate response to anti-CD20 therapy, a persistence of CD20- plasmablasts is noted. The strong expression of CD319 on CD20- plasmablast and plasma cell populations in RA synovium led to the investigation of the potential of CD319 as a therapeutic target.Methods
PDL241, a novel humanized IgG1 monoclonal antibody (mAb) to CD319, was generated and examined for its ability to inhibit immunoglobulin production from plasmablasts and plasma cells generated from peripheral blood mononuclear cells (PBMC) in the presence and absence of RA synovial fibroblasts (RA-SF). The in vivo activity of PDL241 was determined in a human PBMC transfer into NOD scid IL-2 gamma chain knockout (NSG) mouse model. Finally, the ability of PDL241 to ameliorate experimental arthritis was evaluated in a collagen-induced arthritis (CIA) model in rhesus monkeys.Results
PDL241 bound to plasmablasts and plasma cells but not naïve B cells. Consistent with the binding profile, PDL241 inhibited the production of IgM from in vitro PBMC cultures by the depletion of CD319+ plasmablasts and plasma cells but not B cells. The activity of PDL241 was dependent on an intact Fc portion of the IgG1 and mediated predominantly by natural killer cells. Inhibition of IgM production was also observed in the human PBMC transfer to NSG mouse model. Treatment of rhesus monkeys in a CIA model with PDL241 led to a significant inhibition of anti-collagen IgG and IgM antibodies. A beneficial effect on joint related parameters, including bone remodeling, histopathology, and joint swelling was also observed.Conclusions
The activity of PDL241 in both in vitro and in vivo models highlights the potential of CD319 as a therapeutic target in RA. 相似文献35.
Y. Da P.M. VanRaden M. Ron J.E. Beever A. A. Paszek J. Song 《Animal biotechnology》2013,24(1-2):25-35
Abstract Large scale gene mapping efforts in domestic animals have generated and mapped a large number of genetic markers that are useful for mapping quantitative trait and disease loci and for DNA diagnostic purposes such as parentage testing. Marker polymorphism is an important criterion for selecting genetic markers in planning experiment for mapping quantitative trait loci or for DNA diagnostic purposes. Current formulations of marker polymorphism measures are functions of marker allele frequencies. In this study, two measures of marker polymorphism that are available from gene mapping studies and do not require allele frequencies were proposed and analyzed: the observed polymorphic information content (PIC) and the observed family information content (FIC). The observed FIC was more stable than the observed PIC because the observed FIC is unaffected by the variation in the frequency of heterozygous parents. However, both FIC and PIC are dependent on the gene mapping design. The effective number of alleles is recommended as a tool to standardize marker polymorphism measures so that polymorphism of different markers can be compared on an qual basis, and to obtain a new polymorphism measure (such an exclusion probability) from an existing measure (such as FIC). The usage of the effective number of alleles to standardize FIC, PIC and exclusion probabilities is illustrated using genetic markers in a published linkage map. 相似文献
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Fabrizio Villa Ryo Fujisawa Johanna Ainsworth Kohei Nishimura Michael LieALing Georges Lacaud Karim PM Labib 《EMBO reports》2021,22(3)
The eukaryotic replisome is disassembled in each cell cycle, dependent upon ubiquitylation of the CMG helicase. Studies of Saccharomyces cerevisiae, Caenorhabditis elegans and Xenopus laevis have revealed surprising evolutionary diversity in the ubiquitin ligases that control CMG ubiquitylation, but regulated disassembly of the mammalian replisome has yet to be explored. Here, we describe a model system for studying the ubiquitylation and chromatin extraction of the mammalian CMG replisome, based on mouse embryonic stem cells. We show that the ubiquitin ligase CUL2LRR1 is required for ubiquitylation of the CMG‐MCM7 subunit during S‐phase, leading to disassembly by the p97 ATPase. Moreover, a second pathway of CMG disassembly is activated during mitosis, dependent upon the TRAIP ubiquitin ligase that is mutated in primordial dwarfism and mis‐regulated in various cancers. These findings indicate that replisome disassembly in diverse metazoa is regulated by a conserved pair of ubiquitin ligases, distinct from those present in other eukaryotes. 相似文献
37.
Food Biophysics - Engineered biocatalyst and its desired products using nanotechnology has intensified the research in food industries. Zinc oxide (ZnO) nanosheet is designed and prepared; the... 相似文献
38.
Jo Moore Stephen AC Hawkins Anthony R Austin Timm Konold Robert B Green Ian W Blamire Ian Dexter Michael J Stack Melanie J Chaplin Jan PM Langeveld Marion M Simmons Yvonne I Spencer Paul R Webb Michael Dawson Gerald AH Wells 《BMC research notes》2011,4(1):1-13
Background
Escherichia coli O157:H7 is the most common serovar of enterohemorrhagic E. coli associated with serious human disease outbreaks. Cattle are the main reservoir with E. coli O157:H7 inducing hemorrhagic enteritis in persistent shedding beef cattle, however little is known about how this pathogen affects cattle health. Jejunal Hemorrhage Syndrome (JHS) has unclear etiology but the pathology is similar to that described for E. coli O157:H7 challenged beef cattle suggestive that E. coli O157:H7 could be involved. There are no effective treatments for JHS however new approaches to managing pathogen issues in livestock using prebiotics and probiotics are gaining support. The first objective of the current study was to characterize pathogen colonization in hemorrhaged jejunum of dairy cattle during natural JHS outbreaks. The second objective was to confirm the association of mycotoxigenic fungi in feeds with the development of JHS and also to identify the presence of potential mycotoxins. The third objective was to determine the impact of a prebiotic, Celmanax?, or probiotic, Dairyman's Choice? paste, on the cytotoxicity associated with feed extracts in vitro. The fourth objective was to determine the impact of a prebiotic or a probiotic on E. coli O157:H7 colonization of mucosal explants and a bovine colonic cell line in vitro. The final objective was to determine if prebiotic and probiotic feed additives could modify the symptoms that preceded JHS losses and the development of new JHS cases.Findings
Dairy cattle developed JHS after consuming feed containing several types of mycotoxigenic fungi including Fusarium culmorum, F. poae, F. verticillioides, F. sporotrichioides, Aspergillus flavus, Penicillium roqueforti, P. crustosum, P. paneum and P. citrinum. Mixtures of Shiga toxin - producing Escherichia coli (STEC) colonized the mucosa in the hemorrhaged tissues of the cattle and no other pathogen was identified. The STECs expressed Stx1 and Stx2, but more significantly, Stxs were also present in the blood clot blocking the jejunum. Mycotoxin analysis of the corn crop confirmed the presence of fumonisin, NIV, ZEAR, DON, 15-ADON, 3-ADON, NEO, DAS, HT-2 and T-2. Feed extracts were toxic to enterocytes and 0.1% Celmanax? removed the cytotoxicity in vitro. There was no effect of Dairyman's Choice? paste on feed-extract activity in vitro. Fumonisin, T-2, ZEAR and DON were toxic to bovine cells and 0.1% Celmanax? removed the cytotoxicity in vitro. Celmanax? also directly decreased E. coli O157:H7 colonization of mucosal explants and a colonic cell line in a dose-dependent manner. There was no effect of Dairyman's Choice? paste on E. coli O157:H7 colonization in vitro. The inclusion of the prebiotic and probiotic in the feed was associated with a decline in disease.Conclusion
The current study confirmed an association between mycotoxigenic fungi in the feed and the development of JHS in cattle. This association was further expanded to include mycotoxins in the feed and mixtures of STECs colonizing the severely hemorrhaged tissues. Future studies should examine the extent of involvement of the different STEC in the infection process. The prebiotic, Celmanax?, acted as an anti-adhesive for STEC colonization and a mycotoxin binder in vitro. Future studies should determine the extent of involvement of the prebiotic in altering disease. 相似文献39.
Boichard D Chung H Dassonneville R David X Eggen A Fritz S Gietzen KJ Hayes BJ Lawley CT Sonstegard TS Van Tassell CP VanRaden PM Viaud-Martinez KA Wiggans GR;Bovine LD Consortium 《PloS one》2012,7(3):e34130
The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle. 相似文献
40.