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1.
  • Ahanda, Marie-Laure Endale, et al. (författare)
  • Non-coding RNAs revealed during identification of genes involved in chicken immune responses
  • 2009
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 61:1, s. 55-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent large-scale cDNA cloning studies have shown that a significant proportion of the transcripts expressed from vertebrate genomes do not appear to encode protein. Moreover, it was reported in mammals (human and mice) that these non-coding transcripts are expressed and regulated by mechanisms similar to those involved in the control of protein-coding genes. We have produced a collection of cDNA sequences from immunologically active tissues with the aim of discovering chicken genes involved in immune mechanisms, and we decided to explore the non-coding component of these immune-related libraries. After finding known non-coding RNAs (miRNA, snRNA, snoRNA), we identified new putative mRNA-like non-coding RNAs. We characterised their expression profiles in immune-related samples. Some of them showed changes in expression following viral infections. As they exhibit patterns of expression that parallel the behaviour of protein-coding RNAs in immune tissues, our study suggests that they could play an active role in the immune response.
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2.
  • Andersson, Lisa, et al. (författare)
  • The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations
  • 2012
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 64:3, s. 201-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p(raw)=2.34x10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p=0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.
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3.
  • Aveskogh, Maria, et al. (författare)
  • Characterization of cDNA clones encoding mouse proteinase 3 (myeloblastine) and cathepsin G
  • 1997
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 46:3, s. 181-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Serine proteases are the most abundant granule constituents of several major hematopoietic cell lineages. Due to their high abundance and their strict tissue specificity they have become important phenotypic cell markers used for studies of various aspects of hematopietic cell development. Using a polymerase chain reaction (PCR)-based strategy for the isolation of trypsin-related serine proteases, we were able to isolate cDNAs for two of the major neutrophil and monocyte serine proteases in the mouse, cathepsin G and mouse protease 3 (myeloblastin). The internal PCR fragments were used as probes to screen a mouse mast cell cDNA library and a cDNA library originating from a mouse monocytic cell line (WEHI-274.1). Full-length cDNAs for mouse cathepsin G and proteinase 3 were isolated and their complete sequences were determined. Northern blot analysis revealed expression of cathepsin G in immature cells of the monocyte macrophage lineage but also in the connective tissue mast cell line MTC. Proteinase 3 was expressed in several cell lines of myelo-monocytic origin and in one B-cell line, but not in any of the other cell lines tested. The isolation of cDNAs for mouse cathepsin G and mouse proteinase 3, together with the previous characterization of the gene for mouse N-elastase, and the entire or partial amino acid sequences for porcine azurocidine, equine N-elastase and proteinase 3, rat, dog, and rabbit cathepsin Gs in evolutionary relatively distantly related mammalian species, indicates that these four members of the serine protease family have been maintained for more than 100 million years of mammalian evolution. This latter finding indicates a strong evolutionary pressure to maintain specific immune functions associated with these neutrophil and monocyte proteases. All amino acid positions of major importance for the cleavage site selection have also been fully conserved between mouse and human proteinase 3 and a few minor changes have occurred between mouse and human cathepsin G.
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4.
  • Bemark, Mats, et al. (författare)
  • Conserved sequence elements in K promoters from mice and humans : Implications for transcriptional regulation and repertoire expression
  • 1998
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 47:3, s. 183-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Promoter region sequences of human and mouse Igk-V genes were aligned and found to be conserved for about 200-300 base pairs (bp) within subgroups/families. No promoter similarity was found between IGKV promoters from different human subgroups. Related mouse Igk-V gene families were conserved in the promoter region but no similarity was evident when promoters from unrelated Igk-V gene families were compared. Most of the human IGKV promoter subgroups were shown to have mouse counterparts with a similarity region that extended about 150 bp upstream of the translational start codon. All promoters contained an octamer sequence element. The consensus octamer/decamer sequence was favored but only seven residues within the octamer element were strictly conserved. Furthermore, there was also sequence conservation immediately 3' of the octamer where either an A or a G residue was conserved. In addition, other DNA elements were also conserved both within the Igk-V subgroups/families and between mouse and human promoters from related subgroups/families. In several of the subgroups/families an E box of the E2A type was conserved 5' of the octamer and a CCCT element was conserved within the IGKV subgroup II and its related mouse Igk-V families. We conclude from this study that conservation of additional sequence elements besides the octamer is a common feature in Igk-V promoters but that distinct elements are conserved only within a given subgroup/family. Thus, the conservation appears to have operated at the level of function rather than at the level of recognition sequence for defined transcription factors.
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5.
  • Bergman, I. M., et al. (författare)
  • A two-nucleotide deletion renders the mannose-binding lectin 2 (MBL2) gene nonfunctional in Danish Landrace and Duroc pigs
  • 2014
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 66:3, s. 171-184
  • Tidskriftsartikel (refereegranskat)abstract
    • The mannose-binding lectins (MBLs) are central components of innate immunity, facilitating phagocytosis and inducing the lectin activation pathway of the complement system. Previously, it has been found that certain single-nucleotide polymorphisms (SNPs) in porcine MBL1 and MBL2 (pMBL1, pMBL2) affect mRNA expression, serum concentration, and susceptibility to disease, but the combinatory effect of pMBL1 and pMBL2 genotypes needs further elucidation. In the present study, pMBL1 and pMBL2 alleles, combined pMBL haplotypes, and MBL-A concentration in serum were analyzed in purebred Landrace (N = 30) and Duroc (N = 10) pigs. Furthermore, the combined pMBL haplotypes of 89 PiStrain x (Large White x Landrace) crossbred pigs were studied, and the genotypes of 67 crossbreds challenged with Escherichia coli were compared to their individual disease records. In the purebred animals, three non-synonymous SNPs and a two-nucleotide deletion were detected in the coding sequence of pMBL2. The two-nucleotide deletion was present at a frequency of 0.88 in the Landrace pigs and 0.90 in the Duroc pigs, respectively. In the crossbreds, the T allele of the SNP G949T in pMBL1-previously shown to have profound effect on MBL-A concentration even in the heterozygote condition-was detected in 47 % of the animals. Finally, an association was found between low-producing MBL genotypes and low body weight on the day of weaning in the same animals.
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6.
  • Bergman, Ingrid-Maria, 1961-, et al. (författare)
  • European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes
  • 2010
  • Ingår i: Immunogenetics. - : Springer. - 0093-7711 .- 1432-1211. ; 62:1, s. 49-58
  • Tidskriftsartikel (refereegranskat)abstract
    • During the last decade, the Toll-like receptors (TLRs) have been extensively studied and their immense importance in innate immunity is now being unveiled. Here, we report pronounced differences – probably reflecting the domestication process and differences in selective pressure – between wild boars and domestic pigs regarding single nucleotide polymorphisms (SNPs) in TLR genes. The open reading frames of TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace, and Large White origin. In total, 20, 27, and 26 SNPs were detected in TLR1, TLR2, and TLR6, respectively. In TLR1 and TLR2, the numbers of SNPs detected were significantly lower (P ≤ 0.05, P ≤ 0.01) in the wild boars than in the domestic pigs. In the wild boars, one major high frequency haplotype was found in all three genes, while the same pattern was exhibited only by TLR2 in the domestic pigs. The relative frequency of non-synonymous (dN) and synonymous (dS) SNPs was lower for the wild boars than for the domestic pigs in all three genes. In addition, differences in diversity between the genes were revealed: the mean heterozygosity at the polymorphic positions was markedly lower in TLR2 than in TLR1 and TLR6. Because of its localization – in proximity of the bound ligand – one of the non-synonymous SNPs detected in TLR6 may represent species-specific function on the protein level. Furthermore, the codon usage pattern in the genes studied deviated from the general codon usage pattern in Sus scrofa.
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7.
  • Berlin, Sofia, et al. (författare)
  • Positive diversifying selection in avian Mx genes
  • 2008
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 60:11, s. 689-697
  • Tidskriftsartikel (refereegranskat)abstract
    • Mx proteins are interferon-induced GTPases that confer antiviral activities against RNA viruses. We analysed the molecular evolution of the Mx gene in birds using data on interspecific divergence in anseriform and galliform birds, and on intraspecific diversity in commercial chicken lines, local Chinese chicken breeds as well as in the mallard. The overall ratio of non-synonymous to synonymous substitution was unusually high, 0.80, indicating relaxed constraint or positive selection. Evidence for the latter was provided by that a total of 11-18 codons were found to have evolved under positive selection. The great majority of these codons are located in a region unique to birds at the N-terminal end of the Mx protein. We found an excess of non-synonymous polymorphisms relative to synonymous variants in all comparisons. This, together with positive Tajima's D values in the local Chinese chicken breeds and in the mallard suggests that balancing selection is acting in avian Mx genes. As such, Mx mimics the major histocompatibility complex system, indicating that heterozygous individuals are better off withstanding pathogen attack.
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8.
  • Bonneaud, C, et al. (författare)
  • An Mhc class I allele associated to the expression of T-dependent immune response in the house sparrow
  • 2005
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 57:10, s. 782-789
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex (Mhc) encodes for highly variable molecules, responsible for foreign antigen recognition and subsequent activation of immune responses in hosts. Mhc polymorphism should hence be related to pathogen resistance and immune activity, with individuals that carry either a higher diversity of Mhc alleles or one specific Mhc allele exhibiting a stronger immune response to a given antigen. Links between Mhc alleles and immune activity have never been explored in natural populations of vertebrates. To fill this gap, we challenged house sparrows (Passer domesticus) with two T-dependent antigens (phytohemagglutinin and sheep red blood cells) and examined both primary and secondary immune responses in relation to their Mhc class I genotypes. The total number of Mhc alleles had no influence on either primary or secondary response to the two antigens. One particular Mhc allele, however, was associated with an increased response to both antigens. Our results point toward a contribution of the Mhc, or of other genes in linkage disequilibrium with the Mhc, in the regulation of immune responses in a wild animal species.
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9.
  • Bonneaud, C, et al. (författare)
  • Diversity of Mhc class I and IIB genes in house sparrows (Passer domesticus)
  • 2004
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 55:12, s. 855-865
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • In order to understand the expression and evolution of host resistance to pathogens, we need to examine the links between genetic variability at the major histocompatibility complex (Mhc), phenotypic expression of the immune response and parasite resistance in natural populations. To do so, we characterized the Mhc class I and IIB genes of house sparrows with the goal of designing a PCR-based genotyping method for the Mhc genes using denaturing gradient gel electrophoresis (DGGE). The incredible success of house sparrows in colonizing habitats worldwide allows us to assess the importance of the variability of Mhc genes in the face of various pathogenic pressures. Isolation and sequencing of Mhc class I and IIB alleles revealed that house sparrows have fewer loci and fewer alleles than great reed warblers. In addition, the Mhc class I genes divided in two distinct lineages with different levels of polymorphism, possibly indicating different functional roles for each gene family. This organization is reminiscent of the chicken B complex and Rfp-Y system. The house sparrow Mhc hence appears to be intermediate between the great reed warbler and the chicken Mhc, both in terms of numbers of alleles and existence of within-class lineages. We specifically amplified one Mhc class I gene family and ran the PCR products on DGGE gels. The individuals screened displayed between one and ten DGGE bands, indicating that this method can be used in future studies to explore the ecological impacts of Mhc diversity.
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10.
  • Brenden, N., et al. (författare)
  • Differential MHC expression requirements for positive selection of separate TCR Vb families
  • 1999
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 49:1, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6+CD4+ and Vb10+CD4+ thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13+CD8+ thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea→NOD-Ea chimeras have an increased positive selection of Vb13+CD8+ cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6+CD4+ cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10+CD4+ cells was restricted to E-expressing thymic epithelium only. For Vb13+CD8+ cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6+CD4+ cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10+CD4+ cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.
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11.
  • Burri, Reto, et al. (författare)
  • Isolation and characterization of major histocompatibility complex (MHC) class II B genes in the Barn owl (Aves: Tyto alba)
  • 2008
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 60:9, s. 543-550
  • Tidskriftsartikel (refereegranskat)abstract
    • We isolated major histocompatibility complex class II B (MHCIIB) genes in the Barn owl (Tyto alba). A PCR-based approach combined with primer walking on genomic and complementary DNA as well as Southern blot analyses revealed the presence of two MHCIIB genes, both being expressed in spleen, liver, and blood. Characteristic structural features of MHCIIB genes as well as their expression and high non-synonymous substitution rates in the region involved in antigen binding suggest that both genes are functional. MHC organization in the Barn owl is simple compared to passerine species that show multiple duplications, and resembles the minimal essential MHC of chicken.
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12.
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13.
  • Cortazar-Chinarro, Maria, et al. (författare)
  • Signatures of historical selection on MHC reveal different selection patterns in the moor frog (Rana arvalis)
  • 2018
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 70:7, s. 477-484
  • Tidskriftsartikel (refereegranskat)abstract
    • MHC genes are key components in disease resistance and an excellent system for studying selection acting on genetic variation in natural populations. Current patterns of variation in MHC genes are likely to be influenced by past and ongoing selection as well as demographic fluctuations in population size such as those imposed by post-glacial recolonization processes. Here, we investigated signatures of historical selection and demography on an MHC class II gene in 12 moor frog populations along a 1700-km latitudinal gradient. Sequences were obtained from 207 individuals and consecutively assigned into two different clusters (northern and southern clusters, respectively) in concordance with a previously described dual post-glacial colonization route. Selection analyses comparing the relative rates of non-synonymous to synonymous substitutions (dN/dS) suggested evidence of different selection patterns in the northern and the southern clusters, with divergent selection prevailing in the south but uniform positive selection predominating in the north. Also, models of codon evolution revealed considerable differences in the strength of selection: The southern cluster appeared to be under strong selection while the northern cluster showed moderate signs of selection. Our results indicate that the MHC alleles in the north diverged from southern MHC alleles as a result of differential selection patterns.
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14.
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15.
  • Duarte, Nádia, et al. (författare)
  • The Idd6.2 diabetes susceptibility region controls defective expression of the Lrmp gene in nonobese diabetic (NOD) mice
  • 2007
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 59:5, s. 407-416
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of genes mediating susceptibility to type 1 diabetes (T1D) remains a challenging task. Using a positional cloning approach based on the analysis of nonobese diabetic (NOD) mice congenic over the Idd6 diabetes susceptibility region, we found that the NOD allele at this locus mediates lower mRNA expression levels of the lymphoid restricted membrane protein gene (Lrmp/Jaw1). Analysis of thymic populations indicates that Lrmp is expressed mainly in immature thymocytes. The Lrmp gene encodes a type 1 transmembrane protein that localizes to the ER membrane and has homology to the inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate gene, which negatively regulates intracellular calcium levels. We hypothesize that the observed decrease in expression of the Lrmp gene in NOD mice may constitute a T1D susceptibility factor in the Idd6 region.
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16.
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17.
  • Edholm, Eva-Stina, et al. (författare)
  • Identification of Ig sigma and Ig lambda in channel catfish, Ictalurus punctatus, and Ig lambda in Atlantic cod, Gadus morhua
  • 2009
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 61:5, s. 353-370
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunoglobulin light (IGL) chain genes encoding sigma and lambda from channel catfish, Ictalurus punctatus, and lambda from Atlantic cod, Gadus morhua, were identified by mining of expressed sequence tag databases, 5'-RACE and RT-PCR protocols. cDNAs for each of these IGL chains encode typical variable (V), joining (J), and constant (C) regions and Southern blot analyses and genomic sequencing show that genes encoding these isotypes, like other teleost IGL genes, are found in a cluster organization of one or two V gene segments, followed by single J and C gene segments, all in the same transcriptional orientation. However, unlike the teleost kappa genes, genes encoding catfish sigma and lambda are few in number and the two isotypes are each encoded by only two clusters. Similarly, Atlantic cod lambda genes are predicted to be encoded by two or three clusters. As expected, sequence and phylogenetic analyses comparisons demonstrate that catfish V sigma and C sigma genes are most similar to V sigma and C sigma genes of other ectothermic vertebrates. Although catfish and Atlantic cod V lambda genes cluster with other vertebrate V lambda genes, their C lambda sequences cluster in a distinct group separate from other vertebrate IGL C sequences. However, support for classifying these sequences as lambda, is their V and J recombination signal sequence (RSS) organization. The catfish and Atlantic cod genes have typical lambda-like RSS with the V lambda RSS consisting of heptamer-23 bp spacer-nonamer and the J lambda RSS consisting of heptamer-12 bp spacer-nonamer. This is the first report demonstrating the presence of Ig lambda in teleosts.
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18.
  • Ekblom, Robert, et al. (författare)
  • Genetic mapping of the major histocompatibility complex in the zebra finch (Taeniopygia guttata)
  • 2011
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 63:8, s. 523-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Genes of the major histocompatibility complex (MHC) have received much attention in immunology, genetics, and ecology because they are highly polymorphic and play important roles in parasite resistance and mate choice. Until recently, the MHC of passerine birds was not well-described. However, the genome sequencing of the zebra finch (Taeniopygia guttata) has partially redressed this gap in our knowledge of avian MHC genes. Here, we contribute further to the understanding of the zebra finch MHC organization by mapping SNPs within or close to known MHC genes in the zebra finch genome. MHC class I and IIB genes were both mapped to zebra finch chromosome 16, and there was no evidence that MHC class I genes are located on chromosome 22 (as suggested by the genome assembly). We confirm the location in the MHC region on chromosome 16 for several other genes (BRD2, FLOT1, TRIM7.2, GNB2L1, and CSNK2B). Two of these (CSNK2B and FLOT1) have not previously been mapped in any other bird species. In line with previous results, we also find that orthologs to the immune-related genes B-NK and CLEC2D, which are part of the MHC region in chicken, are situated on zebra finch chromosome Z and not among other MHC genes in the zebra finch.
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19.
  • Ekblom, Robert, et al. (författare)
  • Patterns of polymorphism in the MHC class II of a non-passerine bird, the great snipe (Gallinago media)
  • 2003
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 54:10, s. 734-741
  • Tidskriftsartikel (refereegranskat)abstract
    • The genomic organisation of the major histocompatibility complex (MHC) seems to vary considerably between different bird species. In order to understand this variation it is important to gather information from different species. We have, for the first time, investigated MHC class 11 polymorphism in a wader species, the great snipe (Gallinago media). Eleven alleles were found in five sequenced individuals; these come from at least three different loci, but RFLP data suggest that a larger number of genes may be present. For MHC genes, amino acid substitutions followed the, for MHC genes, general pattern of high non-synonymous substitution rates in peptide-binding regions, suggesting that the sequenced alleles may be expressed. The number of genes, lengths of introns and exon sequences of the great snipe MHC seem to be intermediate between those of chicken and passerine birds.
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20.
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21.
  • Follin, Elna, et al. (författare)
  • In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function.
  • 2013
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 65:4, s. 299-311
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1-α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their functional and genetic relationships. We found more pronounced clustering of the MHC class I allomorphs (allele specific proteins) in regards to their function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrow and great reed warbler, although these species diverged 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be ruled out.
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22.
  • Gabdoulkhakova, Aida, et al. (författare)
  • High rate of mutation reporter gene inactivation during human T cell proliferation.
  • 2007
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 59:2, s. 135-143
  • Tidskriftsartikel (refereegranskat)abstract
    • Caspase activation and degradation of deoxyribonucleic acid (DNA) damage response factors occur during in vitro T-cell proliferation, and an increased frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT)-negative variants have been reported in conditions associated with in vivo T-cell proliferation. We have applied two human somatic cell mutation reporter assays, for the HPRT and phosphatidylinositol glycan class A (PIG-A) genes, to human T cells activated in vitro with anti-CD3 and anti-CD28. We demonstrate proliferation throughout 6 weeks of cultivation, and find that the frequency of variant cells phenotypically negative for HPRT and PIG-A, respectively, increases from 10(-5) up to 10(-3)-10(-2). We also report preliminary evidence for low-density CpG methylation in the HPRT promoter suggesting that epigenetic modification may contribute to this markedly heightened rate of gene inactivation.
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23.
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24.
  • Gallwitz, Maike, et al. (författare)
  • Expansion of the mast cell chymase locus over the past 200 million years of mammalian evolution
  • 2006
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 58:8, s. 655-669
  • Tidskriftsartikel (refereegranskat)abstract
    • The acidic granules of natural killer (NK) cells, T cells, mast cells, and neutrophils store large amounts of serine proteases. Functionally, these proteases are involved, e.g., in the induction of apoptosis, the recruitment of inflammatory cells, and the remodeling of extra-cellular matrix. Among the granule proteases are the phylogenetically related mast cell chymases, neutrophil cathepsin G, and T-cell granzymes (Gzm B to H and Gzm N), which share the characteristic absence of a Cys191–Cys220 bridge. The genes of these proteases are clustered in one locus, the mast cell chymase locus, in all previously investigated mammals. In this paper, we present a detailed analysis of the chymase locus in cattle (Bos taurus) and opossum (Monodelphis domestica). The gained information delineates the evolution of the chymase locus over more than 200 million years. Surprisingly, the cattle chymase locus contains two α-chymase and two cathepsin G genes where all other studied chymase loci have single genes. Moreover, the cattle locus holds at least four genes for duodenases, which are not found in other chymase loci. Interestingly, duodenases seem to have digestive rather than immune functions. In opossum, on the other hand, only two chymase locus-related genes have been identified. These two genes are not arranged in one locus, but appear to have been separated by a marsupial-specific chromosomal rearrangement. Phylogenetic analyses place one of the opossum genes firmly with mast cell α-chymases, which indicates that the α-chymase had already evolved as a separate, clearly identifiable gene before the separation of marsupials and placental mammals. In contrast, the second gene in opossum is positioned phylogenetically between granzymes, cathepsin G, and the duodenases. These genes, therefore, probably evolved as separate subfamilies after the separation of placental mammals from marsupials. In platypus, only one chymase locus-like sequence could be identified. This previously published “granzyme” does not cluster clearly with any of the chymase locus gene families, but shares the absence of the Cys191–Cys220 bridge with the other chymase locus proteases. These findings indicate that all chymase locus genes are derived from a single ancestor that was present more than 200 million years ago.
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25.
  • Gallwitz, Maike, et al. (författare)
  • Expression profile of novel members of the rat mast cell protease (rMCP)-2 and (rMCP)-8 families, and functional analyses of mouse mast cell protease (mMCP)-8
  • 2007
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 59:5, s. 391-405
  • Tidskriftsartikel (refereegranskat)abstract
    • Four hematopoietic serine proteases are common to the mast cell chymase locus of all analyzed mammals: α-chymase, cathepsin G, granzyme B, and granzyme C/H. Apart from these common genes, the mouse and rat loci hold additional granzyme-, β-chymase-, and Mcpt8-like genes. To better understand the functional consequences of these additional enzymes and to be able to compare human and rodent immune functions, we have analyzed the expression of novel β-chymase- and Mcpt8-like genes in the rat. Four novel genes, i.e., Mcpt2-rs2a, Mcpt2-rs2c, Mcpt8-rs1, and Mcpt8-rs4 were transcribed in tissues holding mucosal mast cells (MMC), where also the classical MMC protease Mcpt2 was expressed. We also found transcripts of rat vascular chymase (rVch) in some of these tissues. RVch is a β-chymase that converts angiotensin I, like the human chymase. Rat MMC may therefore have similar angiotensin-converting properties as chymase-positive human mast cells, although these are mostly regarded the counterpart of rat connective tissue mast cells. The human mast cells that are considered the counterpart of rat MMC express, however, only tryptase, whereas rat MMC express various proteases, but no tryptase. We further studied the proteolytic activity of mMCP-8 as a first representative for the Mcpt8-subfamily. Based on sequence comparison and molecular modeling, mMCP-8 may prefer aspartic acid in substrate P1 position. However, we could not detect hydrolysis of chromogenic substrates or phage-displayed random nonapeptides despite numerous trials. On the other hand, we have obtained evidence that the function of the Mcpt8-like proteases depends on proteolytic activity. Namely, the expression of the only Mcpt8-family member with a mutation in the catalytic triad, Mcpt8-rs3, was strongly reduced. Thus, the substrate specificity of mMCP-8 may be too narrow to be detected with the employed methods, or the enzyme may require a substrate conformation that is not provided by the analyzed peptides.
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26.
  • Gallwitz, Maike, et al. (författare)
  • Rapid lineage-specific diversification of the mast cell chymase locus during mammalian evolution
  • 2006
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 58:8, s. 641-654
  • Tidskriftsartikel (refereegranskat)abstract
    • Serine proteases constitute the major protein granule content of cells of several hematopoietic cell lineages. A subgroup of these proteases, including the mast cell chymases, neutrophil cathepsin G, and T cell granzymes B to F and N, are in all investigated mammals encoded in one locus, the chymase locus. It is interesting to note that this locus has diversified greatly during the last 95 Myr of mammalian evolution. This divergence is exemplified by the presence of Mcpt8-related genes and multiple beta-chymases in the mouse and rat, which lack direct counterparts in primates and in seven functional granzyme genes in the mouse where the human locus has only two. To study the expansion of the locus during rodent evolution and to better understand the evolutionary origin of beta-chymases and the Mcpt8-family, we have performed a detailed analysis of the chymase locus of four mammalian species, i.e., human, dog, mouse, and rat. As a result, we report here a second chymase-like gene in dog, Cma2, which clusters with beta-chymases in phylogenetic analyses. This finding supports a duplication of the common ancestor for alpha- and beta-chymases before the major radiation of placental mammals, and a loss of the ancestral beta-chymase gene sometime during primate evolution. Moreover, we show that in the rat, the Mcpt8-family diversified relatively recently together with sequences related to the beta-chymase Mcpt2. Eight novel genes were identified in the duplication region, four of which are predicted to be functional. Duplications of rat granzyme B- and C-like sequences occurred seemingly independently within a similar time frame, but did not give rise to functional genes. Due to the duplications in rat and deletions in the carnivore/primate lineage, the rat chymase locus is approximately 15 and 9 times larger than its counterparts in dog and human, respectively. These findings illustrate the importance of gene duplications in conferring rapid changes in mammalian genomes.
  •  
27.
  • Howell, Laura, et al. (författare)
  • A directed miniscreen for genes involved in the Drosophila anti-parasitoid immune response
  • 2012
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 64:2, s. 155-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Drosophila larvae react against eggs from the endoparasitoid wasp Leptopilina boulardi by surrounding them in a multilayered cellular capsule. Once a wasp egg is recognized as foreign, circulating macrophage-like cells, known as plasmatocytes, adhere to the invader. After spreading around the wasp egg, plasmatocytes form cellular junctions between the cells, effectively separating the egg from the hemocoel. Next, a second sub-type of circulating immunosurveillance cell (hemocyte), known as lamellocytes, adhere to either the wasp egg or more likely the plasmatocytes surrounding the egg. From these events, it is obvious that adhesion and cell shape change are an essential part of Drosophila's cellular immune response against parasitoid wasp eggs. To date, very few genes have been described as being necessary for a proper anti-parasitization response in Drosophila. With this in mind, we performed a directed genetic miniscreen to discover new genes required for this response. Many of the genes with an encapsulation defect have mammalian homologues involved in cellular adhesion, wound healing, and thrombosis, including extracellular matrix proteins, cellular adhesion molecules, and small GTPases.
  •  
28.
  • Högstrand, K., et al. (författare)
  • Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions
  • 1999
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 49:5, s. 446-455
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined 32 DNA sequences of mouse and human major histocompatibility complex (MHC) genes believed to have been subjected to gene conversion events. All regions of the mouse H2 genes as well as the human HLA genes which have been implied to be involved in gene conversion events had elevated levels of CpG dinucleotides, whereas the rest of the genes showed extensive CpG suppression. Mouse MHC genes which have been suspected but not directly implied to be involved in gene conversion events also showed elevated levels of CpG dinucleotides. Moreover, both mouse and human MHC genes which have never been suspected of undergoing gene conversion had low levels of CpG throughout the genes. These results indicate that high CpG levels are correlated with gene conversion rather than with polymorphism, as non-polymorphic genes that have been implicated as gene conversion donors also have elevated levels of CpG dimers in the involved regions whereas polymorphic genes which have never been considered to undergo gene conversion events have a low level of CpG dinucleotides. We also studied the methylation pattern of CpG dimers in the Abk gene by restriction enzyme digestion of mouse testis DNA followed by Southern blot and hybridization to an Abk-specific probe. The examined CpG dimers in prepubescent mice, where the latest germline stages are spermatogonia, leptene, or pachytene, are respectively non-methylated. Accordingly, the CpG dimers appear to be non-methylated in germline DNA from the testis of prepubescent mice, where gene conversions have been reported to occur.
  •  
29.
  •  
30.
  • Langefors, Åsa, et al. (författare)
  • Allelic polymorphism in MHC class IIB in four populations of Atlantic salmon (Salmo salar)
  • 2001
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 53:4, s. 329-336
  • Tidskriftsartikel (refereegranskat)abstract
    • We sequenced exon 2 of the MHC class II B gene in Atlantic salmon from the Baltic Sea and identified 17 different exon 2 alleles among 22 different restriction fragment length polymorphism haplotypes. The sequences differed at between I and 34 bases. Two different tests were used to estimate the importance of recombination in the generation of new alleles. Recombination events appear to have occurred between three and nine times. Only two pairs of sequences differed by less than five nucleotides', minimizing the importance of point mutations for generating new alleles. Phylogenetic analysis showed that sequences did not cluster according to populations, and genetic distances between populations were small compared to those obtained by allele frequency data. These results, together with the similarity found between exon 2 sequences from Baltic salmon and Norwegian salmon, indicate that all of the identified alleles were present in the ancient salmon population colonizing the Baltic rivers after the last glaciation.
  •  
31.
  • Lillie, Mette (författare)
  • Molecular characterization of MHC class II in the Australian invasive cane toad reveals multiple splice variants
  • 2016
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 68, s. 449-460
  • Tidskriftsartikel (refereegranskat)abstract
    • The cane toad has gained notoriety for its invasion across the Australian landscape, with significant impacts on the native Australian fauna. The invasion has accelerated over time, with invading cane toads adapted for highly dispersive traits. This, however, has come at the cost of the immune system, with lower investment in some immune functions. To investigate the cane toad's immunogenetics, we characterized four major histocompatibility complex (MHC) class IIA and three MHC class IIB loci. Preliminary observations suggest very low allelic diversity at all loci. We also observed various splice isoforms. One isoform seen at one class IIA and two class IIB loci was missing exon 2, which is essential to peptide binding and presentation. The other isoform, observed at a class IIA locus, is likely to be a soluble MHC product. These results may suggest a significant role of alternative splicing of MHC loci in the Australian cane toad.
  •  
32.
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33.
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34.
  • Musolf, K, et al. (författare)
  • Evolution of MHC-DRB class II polymorphism in the genus Apodemus and a comparison of DRB sequences within the family Muridae (Mammalia : Rodentia)
  • 2004
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 56:6, s. 420-426
  • Tidskriftsartikel (refereegranskat)abstract
    • Allelic diversity at major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection over long periods of time, even across multiple speciation events. Trans-species sharing of MHC alleles among genera has been supported by many studies on mammals and fish, but in rodents, the results are ambiguous. We investigated natural levels of MHC-DRB variability and evolutionary processes in the wood mouse (Apodemus sylvaticus) and the yellow-necked mouse (Apodemus flavicollis), which are common, sympatric murid rodents in European forests. Using single-strand conformation polymorphism analysis and DNA sequencing, 38 DRB exon 2 alleles were detected among 162 A. sylvaticus from nine different locations in Germany and Switzerland, and 15 DRB exon 2 alleles were detected among 60 A. flavicollis from three different locations in northern Germany. There was evidence for balancing selection in both species. Phylogenetic analysis, including additional murid taxa, showed that the DRB exon 2 sequences did not separate according to species, consistent with trans-species evolution of the MHC in these taxa.
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35.
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36.
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37.
  • Pardal, Sara, et al. (författare)
  • Characterization of MHC class I in a long distance migratory wader, the Icelandic black-tailed godwit
  • 2017
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 69:7, s. 463-478
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among researchers in ecology and evolution and have been partly characterized in a wide range of bird species. So far, the main focus has been on species within the bird orders Galliformes and Passeriformes, while Charadriiformes remain vastly underrepresented with only two species studied to date. These two Charadriiformes species exhibit striking differences in MHC-I characteristics and MHC-I diversity. We therefore set out to study a third species within Charadriiformes, the Icelandic subspecies of black-tailed godwits (Limosa limosa islandica). This subspecies is normally confined to parasite-poor environments, and we hence expected low MHC diversity. MHC-I was partially characterized first using Sanger sequencing and then using high-throughput sequencing (MiSeq) in 84 individuals. We verified 47 nucleotide alleles in open reading frame with classical MHC-I characteristics, and each individual godwit had two to seven putatively classical MHC alleles. However, in contrast to previous MHC-I data within Charadriiformes, we did not find any evidence of alleles with low sequence diversity, believed to represent non-classical MHC genes. The diversity and divergence of the godwits MHC-I genes to a large extent fell between the previous estimates within Charadriiformes. However, the MHC genes of the migratory godwits had few sites subject to positive selection, and one possible explanation could be a low exposure to pathogens.
  •  
38.
  • Poorafshar, M, et al. (författare)
  • Identification and structural analysis of four serine proteases in a monotreme, the platypus, Ornithorhynchus anatinus
  • 2000
  • Ingår i: Immunogenetics. - : SPRINGER-VERLAG. - 0093-7711 .- 1432-1211. ; 52:1-2, s. 19-28
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the emergence of the major subfamilies of serine proteases during vertebrate evolution, we present here the primary structure of four serine proteases expressed in the spleen of a monotreme, the platypus, Ornithorhynchus anatinus. Partial cDNA clones for four serine proteases were isolated by a PCR-based strategy. This strategy is based on the high level of sequence identity between various members of the large gene family of trypsin-related serine proteases, over two highly conserved regions, those of the histidine and the serine of the catalytic triad. The partial cDNA clones were used to isolate full-length or almost full-length cDNA clones for three of these proteases from a platypus spleen cDNA library. By phylogenetic analysis, these three clones were identified as being the platypus homologues of human coagulation factor X, neutrophil elastase, and a protease distantly related to the T-cell granzymes. The remaining partial clone was found to represent a close homologue of human complement factor D (adipsin). The isolation of these four clones shows that several of the major subfamilies of serine proteases had evolved as separate subfamilies long before the radiation of the major mammalian lineages of today, the monotremes, the marsupials, and the placental mammals. Upon comparison of the corresponding proteases of monotremes and eutherian mammals, the coagulation and complement proteases were shown to display a higher degree of conservation compared to the hematopoietic proteases N-elastase and the T-cell granzymes. This latter finding indicates a higher evolutionary pressure to maintain specific functions in the complement and coagulation enzymes compared to many of the hematopoietic serine proteases.
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39.
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40.
  • Rabbani, H, et al. (författare)
  • Polymorphism of the IGHG3 gene in cattle
  • 1997
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 46:4, s. 326-331
  • Tidskriftsartikel (refereegranskat)
  •  
41.
  • Reimer, Jenny, et al. (författare)
  • High degree of conservation of the multigene tryptase locus over the past 150-200 million years of mammalian evolution
  • 2010
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 62:6, s. 369-382
  • Tidskriftsartikel (refereegranskat)abstract
    • Activated mast cells release a number of potent inflammatory mediators including histamine, proteoglycans, cytokines, and serine proteases. The proteases constitute the majority of the mast cell granule proteins, and they belong to either the chymase or the tryptase family. In mammals, these enzymes are encoded by two different loci, the mast cell chymase and the multigene tryptase loci. In mice and humans, a relatively large number of tryptic enzymes are encoded from the latter locus. These enzymes can be grouped into two subfamilies, the group 1 tryptases, with primarily membrane-anchored enzymes, and the group 2 tryptases, consisting of the soluble mast cell tryptases. In order to study the appearance of these enzymes during vertebrate evolution, we have analyzed the dog, cattle, opossum, and platypus genomes and sought orthologues in the genomes of several bird, frog, and fish species as well. Our results show that the overall structure and the number of genes within this locus have been well conserved from marsupial to placental mammals. In addition, two relatively distantly related group 2 tryptase genes and several direct homologues of some of the group 1 genes are present in the genome of the platypus, a monotreme. However, no direct homologues of the individual genes of either group 1 or 2 enzymes were identified in bird, amphibian, or fish genomes. Our results indicate that the individual genes within the multigene tryptase locus, in their present form, are essentially mammal-specific.
  •  
42.
  • Ruby, T, et al. (författare)
  • Characterisation of a cluster of TRIM-B30.2 genes in the chicken MHC B locus
  • 2005
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 57:1-2, s. 116-128
  • Tidskriftsartikel (refereegranskat)abstract
    • We have identified and characterised a cluster of six TRIM-B30.2 genes flanking the chicken BF/ BL region of the B complex. The TRIM-B30.2 proteins are a subgroup of the TRIM protein family containing the tripartite motif ( TRIM), consisting of a RING domain, a B-box and a coiled coil region, and a B30.2-like domain. In humans, a cluster of seven TRIM- B30.2 genes has been characterised within the MHC on Chromosome 6p21.33. Among the six chicken TRIM- B30.2 genes two are orthologous to those of the human MHC, and two (TRIM41 and TRIM7) are orthologous to human genes located on Chromosome 5. In humans, these last two genes are adjacent to GNB2L1, a guanine nucleotide-binding protein gene, the ortholog of the chicken c12.3 gene situated in the vicinity of the TRIM-B30.2 genes. This suggests that breakpoints specific to mammals have occurred and led to the remodelling of their MHC structure. In terms of structure, like their mammalian counterparts, each chicken gene consists of five coding exons; exon 1 encodes the RING domain and the B-box, exons 2, 3 and 4 form the coiled- coil region, and the last exon represents the B30.2- like domain. Phylogenetic analysis led us to assume that this extended BF/ BL region may be similar to the human extended class I region, because it contains cluster of BG genes sharing an Ig-V like domain with the BTN genes ( Henry et al. 1997a) and six TRIM-B30.2 genes containing the B30.2-like domain, shared with the TRIM-B30.2 members and the BTN genes.
  •  
43.
  • Schut, Elske, et al. (författare)
  • Characterization of MHC-I in the blue tit (Cyanistes caeruleus) reveals low levels of genetic diversity and trans-population evolution across European populations
  • 2011
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 63:8, s. 531-542
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histcompatibility complex (MHC) is a vital component of the adaptive immune system in all vertebrates. This study is the first to characterize MHC class I (MHC-I) in blue tits (Cyanistes caeruleus), and we use MHC-I exon 3 sequence data from individuals originating from three locations across Europe: Spain, the Netherlands to Sweden. Our phylogeny of the 17 blue tit MHC-I alleles contains one allele cluster with low nucleotide diversity compared to the remaining more diverse alleles. We found a significant evidence for balancing selection in the peptide-binding region in the diverse allele group only. No separation according to geographic location was found in the phylogeny of alleles. Although the number of MHC-I loci of the blue tit is comparable to that of other passerine species, the nucleotide diversity of MHC-I appears to be much lower than that of other passerine species, including the closely related great tit (Parus major) and the severely inbred Seychelles warbler (Acrocephalus sechellensis). We believe that this initial MHC-I characterization in blue tits provides an important step towards understanding the mechanisms shaping MHC-I diversity in natural populations.
  •  
44.
  • Strand, Tanja, et al. (författare)
  • The MHC class II of the Black grouse (Tetrao tetrix) consists of low numbers of B and Y genes with variable diversity and expression
  • 2007
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 59:9, s. 725-734
  • Tidskriftsartikel (refereegranskat)abstract
    • We found that the Black grouse (Tetrao tetrix) possess low numbers of Mhc class II B (BLB) and Y (YLB) genes with variable diversity and expression. We have therefore shown, for the first time, that another bird species (in this case, a wild lek-breeding galliform) shares several features of the simple Mhc of the domestic chicken (Gallus gallus). The Black grouse BLB genes showed the same level of polymorphism that has been reported in chicken, and we also found indications of balancing selection in the peptide-binding regions. The YLB genes were less variable than the BLB genes, also in accordance with earlier studies in chicken, although their functional significance still remains obscure. We hypothesize that the YLB genes could have been under purifying selection, just as the mammal Mhc-E gene cluster.
  •  
45.
  • Strandh, Maria, et al. (författare)
  • Characterization of MHC class I and II genes in a subantarctic seabird, the blue petrel, Halobaena caerulea (Procellariiformes)
  • 2011
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 1432-1211 .- 0093-7711. ; 63:10, s. 653-666
  • Tidskriftsartikel (refereegranskat)abstract
    • The great polymorphism observed in the major histocompatibility complex (MHC) genes is thought to be maintained by pathogen-mediated selection possibly combined with MHC-disassortative mating, guided by MHC-determined olfactory cues. Here, we partly characterize the MHC class I and II B of the blue petrel, Halobaena caerulea (Procellariiformes), a bird with significant olfactory abilities that lives under presumably low pathogen burdens in Subantarctica. Blue petrels are long-lived, monogamous birds which suggest the necessity of an accurate mate choice process. The species is ancestral to songbirds (Passeriformes; many MHC loci), although not to gamefowls (Galliformes; few MHC loci). Considering the phylogenetic relationships and the low subantarctic pathogen burden, we expected few rather than many MHC loci in the blue petrel. However, when we analysed partial MHC class I and class II B cDNA and gDNA sequences we found evidence for as many as at least eight MHC class I loci and at least two class II B loci. These class I and II B sequences showed classical MHC characteristics, e.g. high nucleotide diversity, especially in putative peptide-binding regions where signatures of positive selection was detected. Trans-species polymorphism was found between MHC class II B sequences of the blue petrel and those of thin-billed prion, Pachyptila belcheri, two species that diverged similar to 25 MYA. The observed MHC allele richness in the blue petrel may well serve as a basis for mate choice, especially since olfactory discrimination of MHC types may be possible in this species.
  •  
46.
  •  
47.
  • Tengvall, Katarina, 1980-, et al. (författare)
  • Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin
  • 2020
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 72:5, s. 315-323
  • Tidskriftsartikel (refereegranskat)abstract
    • Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.
  •  
48.
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49.
  • von Salomé, Jenny, et al. (författare)
  • Full-length sequence analysis of the HLA-DRB1 locus suggests a recent origin of alleles
  • 2007
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 59:4, s. 261-271
  • Tidskriftsartikel (refereegranskat)abstract
    • The HLA region harbors some of the most polymorphic loci in the human genome. Among them is the class II locus HLA-DRB1, with more than 400 known alleles. The age of the polymorphism and the rate at which new alleles are generated at HLA loci has caused much controversy over the years. Previous studies have mostly been restricted to the 270 base pairs that constitute the second exon and represent the most variable part of the gene. Here, we investigate the evolutionary history of the HLA-DRB1 locus on the basis of an analysis of 15 genomic full-length alleles (10–15 kb). In addition, the variation in 49 complete coding sequences and 322 exon 2 sequences were analyzed. When excluding exon 2 from the analysis, the diversity at the synonymous sites was found to be similar to the intron diversity. The overall diversity in noncoding region was also similar to the genome average. The DRB1*03 lineage has been found in human, chimpanzee, bonobo, gorilla, and orangutan. An ancestral “proto HLA-DRB1*03 lineage” appeared to have diverged in the last 5 million years into the human-specific lineages *08, *11, *13, and *14. With exception to exon 2, both the coding- and the noncoding diversity suggests a recent origin (<1 million years ago) for most of the alleles at the HLA-DRB1 locus. Sites encoding for amino acids involved in antigen binding [antigen recognizing sites (ARS)] appear to have a more ancient origin. Taken together, the recent origin of most alleles, the high diversity between allelic lineages, and the ancient origin of sequence motifs in exon 2, is consistent with a relatively rapid generation of novel alleles by gene conversion like events.
  •  
50.
  • Vossen, MTM, et al. (författare)
  • Viral immune evasion: a masterpiece of evolution
  • 2002
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 54:8, s. 527-542
  • Tidskriftsartikel (refereegranskat)
  •  
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