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Class II Genes (class + ii_gene)
Kinds of Class II Genes Selected AbstractsTesticular carcinoma and HLA Class II genesCANCER, Issue 9 2002Dirk J. A. Sonneveld M.D., Ph.D. Abstract BACKGROUND The association with histocompatibility antigens (HLA), in particular Class II genes (DQB1, DRB1), has recently been suggested to be one of the genetic factors involved in testicular germ cell tumor (TGCT) development. The current study, which uses genotyping of microsatellite markers, was designed to replicate previous associations. METHODS In 151 patients, along with controls comprising parents or spouses, the HLA region (particularly Class II) on chromosome 6p21 was genotyped for a set of 15 closely linked microsatellite markers. RESULTS In both patients and controls, strong linkage disequilibrium was observed in the genotyped region, indicating that similar haplotypes are likely to be identical by descent. However, association analysis and the transmission disequilibrium test did not show significant results. Haplotype sharing statistics, a haplotype method that derives extra information from phase and single marker tests, did not show differences in haplotype sharing between patients and controls. CONCLUSION The current genotyping study did not confirm the previously reported association between HLA Class II genes and TGCT. As the HLA alleles for which associations were reported are also prevalent in the Dutch populations, these associations are likely to be nonexistent or much weaker than previously reported. Cancer 2002;95:1857,63. © 2002 American Cancer Society. DOI 10.1002/cncr.10903 [source] A recombined haplotype in the major histocompatibility region contains a cluster of genes conferring high susceptibility to ulcerative colitis in the Spanish populationINFLAMMATORY BOWEL DISEASES, Issue 9 2005Laura Fernández PhD Abstract Background: The most consistently described associations in ulcerative colitis (UC) have been with human leukocyte antigen (HLA) class II alleles. Our aim was to look for associations among distinct genetic polymorphisms in the major histocompatibility complex (MHC) that might play a role in determining the susceptibility to UC and especially to the extensive form of the disease. Methods: A case-control study was performed with a total of 253 patients with UC and 315 healthy controls recruited from a single Spanish center. All the samples and 4 cell lines carrying DRB1*0103 or DRB1*1501 alleles were typed for the HLA-DRB1 class II gene and for a panel of HLA class III markers (D6S273, BAT_2, TNFa, b, c, d, e, IKBL+738, MICA). Results: The frequency of the alleles DRB1*0103, IKBL+738(C) (extending our previous results) and BAT_2-8 (newly typed) was increased in patients compared with controls (P = 0.00001, odds ratio [OR] = 5.90; P = 0.002, OR = 2.42; and P = 0.0001, OR = 3.04, respectively), and these associations were greatest in patients with extensive disease compared with patients with distal disease (P = 0.02, OR = 2.53; P = 0.002, OR = 3.06; and P = 0.03, OR = 2.08, respectively). The allelic combination DRB1*0103/D6S273-5/BAT_2-8/TNFa11b4c1d3e3/IKBL+738(C)/MICA5.1 that includes the telomeric class III markers of the 7.1 ancestral haplotype is highly increased in patients with UC (P = 0.0001, OR = 10.57), especially in those with the extensive form of the disease (P = 0.02, OR = 3.41 extensive versus distal). Conclusions: The above-mentioned pattern, most likely formed by recombination of the telomeric fragment of the MHC 7.1 ancestral haplotype, seems to be the most important genetic determinant of susceptibility to the extensive form of UC in our population. [source] Study on association between polymorphism of HLA-DRB1 alleles and Behçet's diseaseJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 12 2009Y-B Shang Abstract Background, Behçet's disease (BD) is known to be associated with human leucocyte antigen (HLA)-B*51 in many ethnic groups. However, the association of HLA class II gene with BD has been described to be different according to different countries and regions. Objective, This study aims to investigate the association between polymorphism of HLA-DRB1 alleles and BD. Methods, Forty patients with BD and 100 healthy controls were typed for HLA-DRB1 alleles by the LABTypeTM SSO method. Results, The frequency of HLA-DRB1*14 was significantly higher in BD patients than in controls (P < 0.05), while the frequency of HLA-DRB1*15 was markedly lower in BD patients (P < 0.05). Regarding clinical manifestations, the frequency of HLA-DRB1*15 was significantly decreased in BD patients with genital ulcerations compared with controls (P < 0.05); the frequency of HLA-DRB1*14 was significantly increased in BD patients with erythema nodosum,like lesions and in BD patients with folliculitis-like lesions when compared to controls (P < 0.05, respectively). Moreover, the frequency of HLA-DRB1*14 was significantly increased in BD patients under 20 years of age at the onset of disease (P < 0.01), while the frequency of HLA-DRB1*15 was significantly decreased in them (P < 0.05), compared with controls. Conclusion, The results suggested that HLA-DRB1 alleles might play an important role in the onset and clinical manifestations of BD. [source] MHC diversity and the association to nematode parasitism in the yellow-necked mouse (Apodemus flavicollis)MOLECULAR ECOLOGY, Issue 7 2005Y. MEYER-LUCHT Abstract In vertebrates, the genes of the major histocompatibility complex (MHC) are among the most debated candidates accounting for co-evolutionary processes of host,parasite interaction at the molecular level. The exceptionally high allelic polymorphism found in MHC loci is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or rare allele advantage (= frequency dependent selection). While investigations under natural conditions are still very rare, studies on humans or mice under laboratory conditions revealed support for both hypotheses. We investigated nematode burden and allelic diversity of a functional important MHC class II gene (DRB exon2) in free-ranging yellow-necked mice (Apodemus flavicollis). Twenty-seven distinct Apfl -DRB alleles were detected in 146 individuals with high levels of amino acid sequence divergence, especially at the antigen binding sites (ABS), indicating selection processes acting on this locus. Heterozygosity had no influence on the infection status (being infected or not), the number of different nematode infections (NNI) or the intensity of infection, measured as the individual faecal egg count (FEC). However, significant associations of specific Apfl -DRB alleles to both nematode susceptibility and resistance were found, for all nematodes as well as in separate analyses of the two most common nematodes. Apodemus flavicollis individuals carrying the alleles Apfl -DRB*5 or Apfl -DRB*15 revealed significantly higher FEC than individuals with other alleles. In contrast, the allele Apfl -DRB*23 showed a significant association to low FEC of the most common nematode. Thus, our results provide evidence for pathogen-driven selection acting through rare allele advantage under natural conditions. [source] Functional interaction of general transcription initiation factor TFIIE with general chromatin factor SPT16/CDC68GENES TO CELLS, Issue 4 2000Seung-Woo Kang Background Transcriptional initiation of class II genes is one of the major targets for the regulation of gene expression and is carried out by RNA polymerase II and many auxiliary factors, which include general transcription initiation factors (GTFs). TFIIE, one of the GTFs, functions at the later stage of transcription initiation. As recent studies indicated the possibility that TFIIE may have a role in chromatin transcriptional regulation, we isolated TFIIE-interacting factors which have chromatin-related functions. Results Using the yeast two-hybrid screening system, we isolated the C-terminal part of the human homologue of Saccharomyces cerevisiae (y) Spt16p/Cdc68p, a general chromatin factor. The C-terminal part of human SPT16/CDC68 directly interacts with TFIIE, and ySpt16p/Cdc68p also interacts with yTFIIE (Tfa1p/Tfa2p), thus indicating the existence of an evolutionarily conserved interaction between TFIIE and SPT16/CDC68. Functional interaction of yTFIIE and ySpt16p/Cdc68p was examined using a conditional yTFIIE-, mutant strain. Over-expression of ySpt16p/Cdc68p suppressed the phenotype of cold sensitivity of the yTFIIE-,- cs mutant strain, and in vitro binding assays revealed that yTFIIE-,- cs mutant protein showed diminished binding affinity to ySpt16p/Cdc68p. Conclusions These observations indicate that general transcription initiation factor TFIIE functionally interacts with general chromatin factor SPT16/CDC68, a finding which provides new insight into the involvement of TFIIE in chromatin transcription. This may well lead to a breakthrough in relationships between the transcription initiation process and structural changes in chromatin. [source] Analysing the effect of novel therapies on cytokine expression in experimental arthritisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2005Richard O. Williams Summary Type II collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Pro-inflammatory cytokines, such as tumour necrosis factor , and interleukin-1,, are expressed in the arthritic joints in both murine CIA and human rheumatoid arthritis, and blockade of these molecules results in amelioration of disease. Hence, there is a great deal of interest in the development of small-molecular-weight inhibitors of pro-inflammatory cytokines. There is also interest in the development and testing of drugs with the capacity to modulate the immune pathways involved in driving the inflammatory response in arthritis. For these reasons, there is a need to monitor the effect of novel treatments on cytokine expression in vivo. In this review, we outline the various techniques used to detect cytokines in experimental arthritis and describe how these techniques have been used to quantify changes in cytokine expression following therapeutic intervention. [source] Sequence-based characterization of the eight SLA loci in Korean native pigsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4-5 2008Y. J. Lee Summary Eight swine leucocyte antigen (SLA) gene (SLA-1, SLA-2, SLA-3, SLA-6, DRA, DRB1, DQA, DQB1) alleles were identified using sequence-based typing method in three Korean native pigs used for breeding at the National Institute of Animal Science in Korea. Six new alleles in class I genes and three new alleles in class II genes have been identified in this breed and can give valuable information for xenotransplantation and disease resistance. [source] A survey of H2 gene sequences, including new wild-derived genesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2007N. A. Mitchison Summary A comprehensive collection of mouse major histocompatibility complex (MHC) promoter and exon 2 sequences is here presented and analysed. It covers the three best known class II genes and one class I gene, and includes new wild mouse sequences from the ,w' back-cross strains and from the Jackson collection. All sequences are in GenBank, and the new exon sequences largely confirm previous typing by serology and immune function. As in human leucocyte antigen (HLA), the overall nucleotide diversity is higher in the class II genes, in keeping with their more diverse function. Diversity along the promoters is highest in the region of known transcription factor binding, most notably in and around the CRE and rCAAT sequences. This distribution parallels that of maximum single nucleotide polymorphism impact previously obtained with reporter constructs. Taking into account the low nucleotide diversity of the CIITA promoter, we conclude that MHC promoters are likely to have diversified through co-evolution with their exons, while themselves also directly subject to natural selection. The H2Ebp alleles form a distinct group, associated with their lack of the recombination hot spot located between exon 2 and exon 3. The collection is expected to prove useful in guiding functional and evolutionary studies. [source] Polymorphism and signature of selection in the MHC class I genes of the three-spined stickleback Gasterosteus aculeatusJOURNAL OF FISH BIOLOGY, Issue 2006H. Schaschl The role and intensity of positive selection maintaining the polymorphism of major histocompatibility complex (MHC) class I genes in the three-spined stickleback Gasterosteus aculeatus was investigated. The highly polymorphic set of MHC class I genes found was organized in a single linkage group. Between 5 and 14 sequence variants per individual were identified by single-stranded conformation polymorphism (SSCP) analysis. Segregation analysis studied in 10 three-spined stickleback families followed the expected pattern of Mendelian inheritance. The gamete fusion in three-spined stickleback thus seems to be random with respect to the MHC class I genes. The DNA sequence analyses showed that the expressed MHC class I loci are under strong selection pressure, possibly mediated by parasites. Codons that were revealed to be under positive selection are potentially important in antigen binding. MHC class I sequences did not form significant supported clusters within a phylogenetic tree. Analogous to MHC class II genes, it was not possible to assign the class I sequences to a specific locus, suggesting that the class I genes may have been generated by recent gene duplication. [source] Genetic drift outweighs balancing selection in shaping post-bottleneck major histocompatibility complex variation in New Zealand robins (Petroicidae)MOLECULAR ECOLOGY, Issue 12 2004HILARY C. MILLER Abstract The Chatham Island black robin, Petroica traversi, is a highly inbred, endangered passerine with extremely low levels of variation at hypervariable neutral DNA markers. In this study we investigated variation in major histocompatibility complex (MHC) class II genes in both the black robin and its nonendangered relative, the South Island robin Petroica australis australis. Previous studies have shown that Petroica have at least four expressed class II B MHC genes. In this study, the sequences of introns flanking exon 2 of these loci were characterized to design primers for peptide-binding region (PBR) sequence analysis. Intron sequences were comprised of varying numbers of repeated units, with highly conserved regions immediately flanking exon 2. Polymerase chain reaction primers designed to this region amplified three or four sequences per black robin individual, and eight to 14 sequences per South Island robin individual. MHC genes are fitness-related genes thought to be under balancing selection, so they may be more likely to retain variation in bottlenecked populations. To test this, we compared MHC variation in the black robin with artificially bottlenecked populations of South Island robin, and with their respective source populations, using restriction fragment length polymorphism analyses and DNA sequencing of the PBR. Our results indicate that the black robin is monomorphic at class II B MHC loci, while both source and bottlenecked populations of South Island robin have retained moderate levels of variation. Comparison of MHC variation with minisatellite DNA variation indicates that genetic drift outweighs balancing selection in determining MHC diversity in the bottlenecked populations. However, balancing selection appears to influence MHC diversity over evolutionary timescales, and the effects of gene conversion are evident. [source] Mammalian Expression Cloning of Two Human Trophoblast Suppressors of Major Histocompatibility Complex GenesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2001J. A. PEYMAN PROBLEM: Human trophoblasts suppress interferon-, (IFN-,)-simulated expression of major histocompatibility complex (MHC) class II genes and thereby protect the conceptus from maternal immune attack. The mechanism of this suppression is poorly understood. METHOD OF STUDY: IFN-,-responsive HeLa cells were stably transfected with trophoblast cDNA expression libraries and screened by negative immunoselection with an antibody to HLA-DR. RESULTS: Two suppressor cDNAs were isolated. One encoded the untranslated RNA trophoblast STAT utron (TSU), which blocked STAT1 nuclear translocation and can theoretically form triplex RNA,DNA at the class II transactivator gene promoters. The other encoded the N-terminal 28 residues of chorionic somatomammotropin (hCS). TSU-related genes were detected in human and macaque, but not in mouse, genomic DNA. CONCLUSIONS: The genetics of two human trophoblast MHC suppressors suggest that these functions have been gained in human placenta in recent evolutionary history. TSU and hCS play critical roles in suppression of MHC genes, which may lead to silencing by DNA methylation. [source] Molecular characterization of swine leucocyte antigen class II genes in outbred pig populationsANIMAL GENETICS, Issue 4 2010C.-S. Ho Summary The highly polymorphic swine leucocyte antigen (SLA) genes are among the most important determinants of swine immune responses to disease and vaccines. Accurate and effective SLA genotyping methods are required to understand how SLA gene polymorphisms affect immunity, especially in outbred pigs with diverse genetic backgrounds. In this study, we present a simple and rapid molecular-based typing system for characterizing SLA class II alleles of the DRB1, DQB1 and DQA loci. This system utilizes a set of 47 sequence-specific PCR primers developed to differentiate alleles by groups that share similar sequence motifs. We applied this typing method to investigate the SLA class II diversity in four populations of outbred pigs (n = 206) and characterized a total of 19 SLA class II haplotypes, six of which were shared by at least three of the sampled pig populations. We found that Lr-0.1 (DRB1*01XX,DQB1*01XX,DQA*01XX) was the most prevalent haplotype with a combined frequency of 16.0%, followed by Lr-0.2 (DRB1*02XX,DQB1*02XX,DQA*02XX) with 14.6% and Lr-0.15b (DRB1*04XX,DQB1*0202,DQA*02XX) with 14.1%. Over 70% of the pigs (n = 147) had at least one copy of one of these three haplotypes. The PCR-based typing system described in this study demonstrates a reliable and unambiguous detection method for SLA class II alleles. It will be a valuable tool for studying the influence of SLA diversity on various immunological, pathological and physiological traits in outbred pigs. [source] cDNA cloning and genetic polymorphism of the swine major histocompatibility complex (SLA) class II DMA geneANIMAL GENETICS, Issue 2 2001A. Ando cDNA clones corresponding to the swine histocompatibility complex (SLA: swine leucocyte antigen)-DM , chain were isolated using the polymerase chain reaction (PCR) products from the third exon in the human HLA-DMA gene as a probe. Amino acid comparative analysis revealed that these clones were more closely related to the bovine and human DMA genes than to the other swine class II genes , chain genes, DRA, DQA and DOA. These results suggest that the SLA-DMA gene is expressed and may function, like HLA-DM, as an important modulator in class II restricted antigen processing in swine. Furthermore, based on the sequences and PCR,restriction fragment length polymorphism (PCR,RFLP) patterns in the SLA-DMA gene, no allelic variation was recognized in the second exon, but five allelic variations were recognized in the third exon in five different breeds of swine. These DMA alleles were defined by variation at four nucleotide positions. Two of these alleles resulted in an amino acid substitution. These results suggest that SLA-DMA has little polymorphism as observed in HLA-DMA and mouse H2-Ma. [source] Structure, function and disease susceptibility of the bovine major histocompatibility complexANIMAL SCIENCE JOURNAL, Issue 2 2006Shin-Nosuke TAKESHIMA ABSTRACT The major histocompatibility complex (MHC) of cattle is known as the bovine leukocyte antigen (BoLA) and is located on chromosome 23. BoLA has been linked to variation in resistance to disease including bovine leukemia virus-induced lymphoma and mastitis. Moreover, BoLA appears to influence other traits such as milk yield, growth and reproduction, which are not often measured in humans, and variations in individual immune response to antigen. The BoLA appears to be organized in a similar way to the MHC region in humans, but there are notable differences. A major rearrangement within the class II region has led to the division of the BoLA into two distinct subregions of chromosome 23 separated by about a third of the chromosome's length. The class IIa subregion contains functionally expressed DR and DQ genes, while the class IIb subregion contains the genes of undefined status such as DYA, DYB, DMA, DMB, DOB, DOA, TAP1, TAP2, LAP2 and LMP7. In addition, one pair of human class II genes (DP) does not appear to have an equivalent in cattle, and there is one pair of DY genes that seem to be found only cattle, sheep and goats. In humans, three classical, polymorphic class I genes (HLA-A, -B and -C,) are each present on all haplotypes. However, in cattle, none of the four (or more) classical class-I genes identified are consistently expressed, and haplotypes differ from one to another in both the gene number and composition. These variations in both class I and II are likely to play an important role in cattle immune responses. This review summarizes current knowledge of the structural and functional features and disease association of BoLA genes. [source] HLA DPB1*0201 allele is negatively associated with immunoglobulin E responsiveness specific for house dust mite allergens in TaiwanCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2000Background House dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen-specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM. Objective This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus. Methods Two hundred and forty-eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) -specific IgE and Der p 2-specific IgG antibodies were detected by ELISA, while HLA class II -DRB1, -DQA1, -DQB1, -DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen-specific IgE and IgG antibodies were performed. Results There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM-specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5-specific IgE responsiveness. However, we found that HLA-DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA-DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P , 0.0001, P , 0.0007, Pc , 0.010). Conclusion We clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA-DPB1*0201 involvement in protecting subjects from HDM-specific IgE responsiveness awaits further investigation. [source] | |||||||||||||||||||||||||