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排序方式: 共有133条查询结果,搜索用时 15 毫秒
1.
Anthony T Papenfuss Zhi-Ping Feng Katina Krasnec Janine E Deakin Michelle L Baker Robert D Miller 《BMC genomics》2015,16(1)
Background
Major histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates. The evolution of this gene family is closely tied to the evolution of the vertebrate genome. Family members are frequently found in four paralogous regions, which were formed in two rounds of genome duplication in the early vertebrates, but in some species class Is have been subject to additional duplication or translocation, creating additional clusters. The gene family is traditionally grouped into two subtypes: classical MHC class I genes that are usually MHC-linked, highly polymorphic, expressed in a broad range of tissues and present endogenously-derived peptides to cytotoxic T-cells; and non-classical MHC class I genes generally have lower polymorphism, may have tissue-specific expression and have evolved to perform immune-related or non-immune functions. As immune genes can evolve rapidly and are subject to different selection pressure, we hypothesised that there may be divergent, as yet unannotated or uncharacterised class I genes.Results
Application of a novel method of sensitive genome searching of available vertebrate genome sequences revealed a new, extensive sub-family of divergent MHC class I genes, denoted as UT, which has not previously been characterized. These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage. We show that UT family members are expressed in the thymus of the gray short-tailed opossum and in other immune tissues of several Australian marsupials. Structural homology modelling shows that the proteins encoded by this family are predicted to have an open, though short, antigen-binding groove.Conclusions
We have identified a novel sub-family of putatively non-classical MHC class I genes that are specific to marsupials and monotremes. This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage. The function of this family is as yet unknown, however, their predicted structure may be consistent with presentation of antigens to T-cells.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1745-4) contains supplementary material, which is available to authorized users. 相似文献2.
Carmen S. M. Yong Janelle Sharkey Belinda Duscio Ben Venville Wei-Zen Wei Richard F. Jones Clare Y. Slaney Gisela Mir Arnau Anthony T. Papenfuss Jan Schr?der Phillip K. Darcy Michael H. Kershaw 《PloS one》2015,10(9)
The development of antigen-targeted therapeutics is dependent on the preferential expression of tumor-associated antigens (TAA) at targetable levels on the tumor. Tumor-associated antigens can be generated de novo or can arise from altered expression of normal basal proteins, such as the up-regulation of human epidermal growth factor receptor 2 (Her2/ErbB2). To properly assess the development of Her2 therapeutics in an immune tolerant model, we previously generated a transgenic mouse model in which expression of the human Her2 protein was present in both the brain and mammary tissue. This mouse model has facilitated the development of Her2 targeted therapies in a clinically relevant and suitable model. While heterozygous Her2+/- mice appear to develop in a similar manner to wild type mice (Her2-/-), it has proven difficult to generate homozygous Her2+/+ mice, potentially due to embryonic lethality. In this study, we performed whole genome sequencing to determine if the integration site of the Her2 transgene was responsible for this lethality. Indeed, we report that the Her2 transgene had integrated into the Pds5b (precocious dissociation of sisters) gene on chromosome 5, as a 162 copy concatemer. Furthermore, our findings demonstrate that Her2+/+ mice, similar to Pds5b-/- mice, are embryonic lethal and confirm the necessity for Pds5b in embryonic development. This study confirms the value of whole genome sequencing in determining the integration site of transgenes to gain insight into associated phenotypes. 相似文献
3.
Marcelo H Ratto Louis TJ Delbaere Yvonne A Leduc Roger A Pierson Gregg P Adams 《Reproductive biology and endocrinology : RB&E》2011,9(1):24
Background
The objective of the present study was to isolate and purify the protein fraction(s) of llama seminal plasma responsible for the ovulation-inducing effect of the ejaculate. 相似文献4.
California is a biodiversity hotspot facing unbridled human population growth, especially in Central California. One of the
poorly known, sensitive species in this area is the California legless lizard (Anniella pulchra), a fossorial worm-like reptile. We report mt and nuDNA sequences from 69 museum-vouchered samples of Anniella (A. pulchra and its sister species A. geronimensis) from 48 localities. Our genetic survey reveals substantially more genetic diversity within A. pulchra than previously reported. Our two independently evolving markers (mt and nuDNA) reveal five major lineages of A. pulchra. Two of the five major lineages of A. pulchra correspond to a north-south split found in other widespread California reptiles. These northern and southern clades also
correspond to a previous study showing variation in chromosomal number. Unlike most other Californian reptiles, A. pulchra has major genetic lineages that are endemic to Central California including two that are endemic to the San Joaquin Valley
and Carrizo Plain. Although A. pulchra is threatened throughout its range, the distinct San Joaquin lineages are seriously imperiled by urban sprawl. Some of the
localities for the newly recognized genetic lineages have already been destroyed by development. 相似文献
5.
6.
Emily S. W. Wong Claire E. Sanderson Janine E. Deakin Camilla M. Whittington Anthony T. Papenfuss Katherine Belov 《Immunogenetics》2009,61(8):565-579
Natural killer (NK) cell receptors belong to two unrelated, but functionally analogous gene families: the immunoglobulin superfamily,
situated in the leukocyte receptor complex (LRC) and the C-type lectin superfamily, located in the natural killer complex
(NKC). Here, we describe the largest NK receptor gene expansion seen to date. We identified 213 putative C-type lectin NK
receptor homologs in the genome of the platypus. Many have arisen as the result of a lineage-specific expansion. Orthologs
of OLR1, CD69, KLRE, CLEC12B, and CLEC16p genes were also identified. The NKC is split into at least two regions of the genome: 34 genes map to chromosome 7, two map
to a small autosome, and the remainder are unanchored in the current genome assembly. No NK receptor genes from the LRC were
identified. The massive C-type lectin expansion and lack of Ig-domain-containing NK receptors represents the most extreme
polarization of NK receptors found to date. We have used this new data from platypus to trace the possible evolutionary history
of the NK receptor clusters.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
7.
Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites 下载免费PDF全文
Jake Baum Anthony T. Papenfuss Gunnar R. Mair Chris J. Janse Dina Vlachou Andrew P. Waters Alan F. Cowman Brendan S. Crabb Tania F. de Koning-Ward 《Nucleic acids research》2009,37(11):3788-3798
Techniques for targeted genetic disruption in Plasmodium, the causative agent of malaria, are currently intractable for those genes that are essential for blood stage development. The ability to use RNA interference (RNAi) to silence gene expression would provide a powerful means to gain valuable insight into the pathogenic blood stages but its functionality in Plasmodium remains controversial. Here we have used various RNA-based gene silencing approaches to test the utility of RNAi in malaria parasites and have undertaken an extensive comparative genomics search using profile hidden Markov models to clarify whether RNAi machinery exists in malaria. These investigative approaches revealed that Plasmodium lacks the enzymology required for RNAi-based ablation of gene expression and indeed no experimental evidence for RNAi was observed. In its absence, the most likely explanations for previously reported RNAi-mediated knockdown are either the general toxicity of introduced RNA (with global down-regulation of gene expression) or a specific antisense effect mechanistically distinct from RNAi, which will need systematic analysis if it is to be of use as a molecular genetic tool for malaria parasites. 相似文献
8.
9.
Sara Rosati Ewald TJ van den Bremer Janine Schuurman Paul WHI Parren Johannis P Kamerling Albert JR Heck 《MABS-AUSTIN》2013,5(6):917-924
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies 相似文献
10.
TJ Beveridge 《Biotechnic & histochemistry》2001,76(3):111-118
The Gram stain differentiates bacteria into two fundamental varieties of cells. Bacteria that retain the initial crystal violet stain (purple) are said to be 'Gram-positive,' whereas those that are decolorized and stain red with carbol fuchsin (or safranin) are said to be 'Gram-negative.' This staining response is based on the chemical and structural makeup of the cell walls of both varieties of bacteria. Gram-positives have a thick, relatively impermeable wall that resists decolorization and is composed of peptidoglycan and secondary polymers. Gram-negatives have a thin peptidoglycan layer plus an overlying lipid-protein bilayer known as the outer membrane, which can be disrupted by decolorization. Some bacteria have walls of intermediate structure and, although they are officially classified as Gram-positives because of their linage, they stain in a variable manner. One prokaryote domain, the Archaea, have such variability of wall structure that the Gram stain is not a useful differentiating tool. 相似文献