Genomic location and characterisation of nonclassical MHC class I genes in cattle
Immunology Division, Institute for Animal Health, Compton RG20 7NN, UK. Immunogenetics
(Impact Factor: 2.23).
06/2008; 60(5):267-73. DOI: 10.1007/s00251-008-0294-2
The cattle major histocompatibility complex (MHC) region contains a variable number of classical class I genes encoding polymorphic, ubiquitously expressed molecules with a role in antigen presentation. Class I cDNA sequences have previously been reported that are thought to derive from putative nonclassical class I genes. We have located four nonclassical class I genes within the cattle genome; three are close to the MIC genes, and one is close to the classical class I genes. The genomic position relative to anchor genes is very similar to the arrangement reported in the pig MHC region. We have designed gene-specific oligonucleotide primers with which to investigate the presence of these genes in distinct and well-defined MHC haplotypes and to assess transcription in different cell types. Analysis and comparison of all sequences allows an assessment of allelic variation in each case. Partial characterisation gives an indication of the possible role and likely importance of each of these genes.
Available from: John Schwartz
- "Comparison of previously published cattle genome assemblies (Birch et al. 2008; Ellis and Hammond 2014) with the assembly in this study. Gaps within each assembly are indicated by broken lines. "
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ABSTRACT: In cattle, there are six classical MHC class I genes that are variably present between different haplotypes. Almost all known haplotypes contain between one and three genes, with an allele of Gene 2 present on the vast majority. However, very little is known about the sequence and therefore structure and evolutionary history of this genomic region. To address this, we have refined the MHC class I region in the Hereford cattle genome assembly and sequenced a complete A14 haplotype from a homozygous Holstein. Comparison of the two haplotypes revealed extensive variation within the MHC class Ia region, but not within the flanking regions, with each gene contained within a conserved 63- to 68-kb sequence block. This variable region appears to have undergone block gene duplication and likely deletion at regular breakpoints, suggestive of a site-specific mechanism. Phylogenetic analysis using complete gene sequences provided evidence of allelic diversification via gene conversion, with breakpoints between each of the extracellular domains that were associated with high guanine-cytosine (GC) content. Advancing our knowledge of cattle MHC class I evolution will help inform investigations of cattle genetic diversity and disease resistance.
Available from: Juliana Pinto da Silva Mol
- "NC1 had low levels of transcription both in the placentome and intercotyledonary tissues throughout the gestation, which is similar to a previous report (Shu et al., 2012). Although the function of bovine NC1 is largely unknown, it is thought that NC1, with its large number of splicing variants (Birch et al., 2008b), generates proteins that are anchored in the membrane or soluble, which may modulate immune tolerance in cattle (Davies et al., 2006). "
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ABSTRACT: Transcription of non-classical major histocompatibility complex class I (MHC-I) was assessed in the bovine placenta throughout gestation. Additionally, the effect of Brucella abortus infection on expression of non-classical MHC-I was also evaluated using a chorioallantoic membrane explant model of infection. The non-classical MHC-I genes MICB and NC3 had higher levels of transcription in the intercotyledonary region when compared to the placentome, which had higher levels of transcription at the second trimester of gestation. NC1 and classical MHC-I had very low levels of transcription throughout gestation. Trophoblastic cells of B. abortus-infected chorioallantoic membrane explants had an increase in transcription of non-classical MHC-I at 4h post infection. Therefore, this study provides an analysis of non-classical MHC-I transcription at different stages of gestation and different placental tissues, and during B. abortus infection. These findings provide additional knowledge on immune regulation in placental tissues, a known immune-privileged site.
Copyright © 2015. Published by Elsevier B.V.
Available from: John A Hammond
- "There are two sequences suffixed 'N' for 'null', N*03201N and N*03301N. In addition, there are 17 non-classical (NC) MHC class I sequences already assigned to mapped genes (NC1–NC4, Birch et al. 2008). NC1 currently has eight alleles plus a number of splice variants, NC2 has three alleles, NC3 has a single allele and NC4 has four alleles. "
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ABSTRACT: The cattle major histocompatibility complex (MHC) region contains a variable number of classical class I genes encoding polymorphic molecules involved in antigen presentation. Six classical class I genes have been described, but assigning sequences to these genes has proved problematic. We propose a refinement of the existing nomenclature, which currently names the 97 known classical class I sequences in a single series. Phylogenetic analysis of the 3' portion of the coding region allows segregation of these into six groups; thus, we have prefixed existing names with the appropriate number. Although it is clear that some of these groups correspond to discrete genes, it is currently not possible to state definitively that all do. However, the main groupings are consistent, and in conjunction with other evidence, we feel it is now appropriate to rename the sequences accordingly. Segregation of sequences into groups in this way will facilitate ongoing research and future use of the cattle MHC section of the Immuno Polymorphism Database.
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