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MHC Region (mhc + region)
Selected AbstractsMHC and Preferences for Male Odour in the Bank VoleETHOLOGY, Issue 9 2008Jacek Radwan Highly polymorphic major histocompatibility complex (MHC) genes are thought to play a central role in the choice of genetically compatible sexual partners in some vertebrates, although the evidence is variable across species. Here, we investigate the association between similarity in the MHC region and sexual preferences in the bank vole Myodes (=Clethrionomys) glareolus (Arvicollinae) in a laboratory setting. Females in post-partum oestrus were given the choice between the scents of two males in a Y-maze. Both males were unrelated to the female, but differed in their MHC similarity to the female. We found that females spent more time near the scent of MHC dissimilar males than those, with whom they shared MHC alleles. This suggests that bank voles use MHC-related cues to choose compatible mates. [source] Identification of novel single nucleotide polymorphisms within the NOTCH4 gene and determination of association with MHC allelesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2003R. Tazi-Ahnini Summary Mapping of disease susceptibility loci within the MHC has been partly hampered by the high degree of polymorphism of the HLA genes and the high level of linkage disequilibrium (LD) between markers within the MHC region. It is therefore important to identify new markers and determine the level of LD between HLA alleles and non-HLA genes. The NOTCH4 gene lies at the centromeric end of the MHC class III region, approximately 335 kb telomeric of the DRB1 locus. The encoded protein is an oncogene that is important in regulating vascular development and remodelling. A recent report has linked polymorphisms within NOTCH4 with risk of developing schizophrenia. We have investigated if coding polymorphisms exist within this gene and have identified three single nucleotide polymorphisms; a synonomous T to C transition at +1297 (HGBASE accession number SNP000064386), a synonomous A to G transition at +3061 (SNP000064387) and an A to G transition at +3063 which results in a replacement of glycine with aspartic acid at amino acid 279 (SNP000064388). The allele frequencies of +1297T, +3061A and +3063G were 0.65, 0.66 and 0.66, respectively. Linkage disequilibrium was detected both between these markers and with MHC alleles. These findings can be used in the fine mapping of disease susceptibility alleles within the MHC. [source] MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic originJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2009Edward T. Mee Abstract Background, Mauritian cynomolgus macaques have greatly restricted genetic diversity in the MHC region compared to other non-human primates; however, the frequency of common MHC haplotypes among captive-bred populations has not been reported. Methods, Microsatellite PCR was used to determine MHC haplotype frequencies among captive macaques at a UK breeding facility. Allele-specific PCR and reference strand conformational analysis were used to determine the allele expression profile of a subset of animals. Results, Haplotypes H3 (21%) and H1 (19%) were most common in the captive population of Mauritian cynomolgus macaques. Predicted alleles were detected by allele-specific PCR-SSP in 98% of animals. Allele expression profiles were similar in animals with identical haplotypes. Conclusions, Mauritian cynomolgus macaques in the UK breeding facility have restricted MHC diversity comparable to a previously described population. Microsatellite-derived haplotypes are highly predictive of allele expression. A selective breeding program has been established to produce MHC-identical animals for biomedical research. [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] Detection of arthritis-susceptibility loci, including Ncf1, and variable effects of the major histocompatibility complex region depending on genetic background in ratsARTHRITIS & RHEUMATISM, Issue 2 2009Carola Rintisch Objective To characterize the arthritis-modulating effects of 3 non,major histocompatibility complex (MHC) quantitative trait loci (QTLs) in rat experimental arthritis in the disease-resistant E3 strain, and to investigate the disease-modulating effects of the MHC region (RT1) in various genetic backgrounds. Methods A congenic fragment containing Ncf1 along with congenic fragments containing the strongest remaining loci, Pia5/Cia3 and Pia7/Cia13 on chromosome 4, were transferred from the arthritis-susceptible DA strain into the background of the completely resistant E3 strain. The arthritis-regulatory potential of the transferred alleles was evaluated by comparing the susceptibility to experimental arthritis in congenic rats with that in E3 rats. The RT1u haplotype from the E3 strain was transferred into the susceptible DA strain (RT1av1), and various F1 and F2 hybrids were generated to assess the effects of RT1 on arthritis susceptibility. Results The DA allele of Ncf1 did not break the arthritis resistance of the E3 rats, although it led to enhanced autoimmune B cell responses, as indicated by significantly elevated levels of anticollagen antibodies in congenic rats. Introgressing Pia5 and Pia7 loci on chromosome 4 broke the resistance to arthritis, and the MHC locus on chromosome 20 in DA rats enhanced arthritis when RT1 interacted with E3 genes. Conclusion The findings in these congenic lines confirm the existence of 3 major QTLs that regulate the severity of arthritis and are sufficient to induce the transformation of a completely arthritis-resistant rat strain into an arthritis-susceptible strain. This study also reveals a dramatic difference in the arthritis-regulatory potential of the rat MHC depending on genetic background, suggesting that strong epistatic interactions occur between MHC and non-MHC genes. [source] Genetic association of the major histocompatibility complex with rheumatoid arthritis implicates two non-DRB1 lociARTHRITIS & RHEUMATISM, Issue 1 2009Charlotte Vignal Objective The HLA,DRB1 locus within the major histocompatibility complex (MHC) at 6p21.3 has been identified as a susceptibility gene for rheumatoid arthritis (RA); however, there is increasing evidence of additional susceptibility genes in the MHC region. The aim of this study was to estimate their number and location. Methods A case,control study was performed involving 977 control subjects and 855 RA patients. The HLA,DRB1 locus was genotyped together with 2,360 single-nucleotide polymorphisms in the MHC region. Logistic regression was used to detect DRB1-independent effects. Results After adjusting for the effect of HLA,DRB1, 18 markers in 14 genes were strongly associated with RA (P < 10,4). Multivariate logistic regression analysis of these markers and DRB1 led to a model containing DRB1 plus the following 3 markers: rs4678, a nonsynonymous change in the VARS2L locus, ,1.7 Mb telomeric of DRB1; rs2442728, upstream of HLA,B, ,1.2 Mb telomeric of DRB1; and rs17499655, located in the 5,-untranslated region of DQA2, only 0.1 Mb centromeric of DRB1. In-depth investigation of the DQA2 association, however, suggested that it arose through cryptic linkage disequilibrium with an allele of DRB1. Two non,shared epitope alleles were also strongly associated with RA (P < 10,4): *0301 with anti, cyclic citrullinated peptide,negative RA and *0701 independently of autoantibody status. Conclusion These results confirm the polygenic contribution of the MHC to RA and implicate 2 additional non-DRB1 susceptibility loci. The role of the HLA,DQ locus in RA has been a subject of controversy, but in our data, it appears to be spurious. [source] Pinpointing a selective sweep to the chimpanzee MHC class I region by comparative genomicsMOLECULAR ECOLOGY, Issue 8 2008NATASJA G. DE GROOT Abstract Chimpanzees experienced a reduction of the allelic repertoire at the major histocompatibility complex (MHC) class I A and B loci, which may have been caused by a retrovirus belonging to the simian immunodeficiency virus (SIV) family. Extended MHC haplotypes were defined in a pedigreed chimpanzee colony. Comparison of genetic variation at microsatellite markers mapping inside and outside the Mhc region was carried out in humans and chimpanzees to investigate the genomic extent of the repertoire reduction. Multilocus demographic analyses underscored that chimpanzees indeed experienced a selective sweep that mainly targeted the chromosomal segment carrying the Mhc class I region. Probably due to genetic linkage, the sweep also affected other polymorphic loci, mapping in the close vicinity of the Mhc class I region genes. Nevertheless, although the allelic repertoire at particular Mhc class I and II loci appears to be limited, naturally occurring recombination events allowed the establishment of haplotype diversity after the sweep. However, recombination did not have sufficient time to erase the signal of the selective sweep. [source] | |||||||||||||