Comparative analysis of the bovine MHC class IIb sequence¹ identifies inversion breakpoints and three unexpected genes

Abstract

The bovine major histocompatibility complex (MHC) or BoLA is organized differently from typical mammalian MHCs in that a large portion of the class II region, called class IIb, has been transposed to a position near the centromere on bovine chromosome 23. Gene mapping indicated that the rearrangement resulted from a single inversion, but the boundaries and gene content of the inverted segment have not been fully determined. Here, we report the genomic sequence of BoLA IIb. Comparative sequence analysis with the human MHC revealed that the proximal inversion breakpoint occurred approximately 2.5 kb from the 3' end of the glutamate-cysteine ligase, catalytic subunit (GCLC) locus and that the distal breakpoint occurred about 2 kb from the 5' end from a divergent class IIDRbeta-like sequence designated DSB. Gene content, order and orientation of BoLA IIb are consistent with the single inversion hypothesis when compared with the corresponding region of the human class II MHC (HLA class II). Differences with HLA include the presence of a single histone H2B gene located between the proteasome subunit, beta type, 9 (PSMB9) and DMB loci and a duplicated TAP2 with a variant splice site. BoLA IIb spans approximately 450 kb DNA, with 20 apparently intact genes and no obvious pseudogenes. The region contains 227 simple sequence repeats (SSRs) and approximately 167 kb of retroviral-related repetitive DNA. Nineteen of the 20 genes identified in silico are supported by bovine EST data indicating that the functional gene content of BoLA IIb has not been diminished because it has been transposed from the remainder of BoLA genes.

Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows

“…The DY genes, which are at the start of the class IIb region and were found residing in the QTL detected for the NVL phenotype, are unique to ruminants and may have a specialised role in antigen presentation to ruminant dendritic cells [25]. The other BoLA classes, including class IIa , are separated from class IIb by ~17 Mb of sequence on BTA23 due to an historical inversion event [26]. Although no associations with M. bovis susceptibility were detected for the other BoLA classes in the current or other bTB studies, it is clear that the BoLA class II alleles influence recognition of M. bovis T cell epitopes [16].…”

Isolation of a 97-kb Minimal Essential MHC B Locus from a New Reverse-4D BAC Library of the Golden Pheasant

“…Due to its important role in immunity and its exceptionally high level of genetic variation, the MHC has attracted considerable attention from many different fields of biological researches, especially for mammals [6]. The mammalian MHC region always occupies more than half a million kilobases in length, as revealed in human [7], cow [8], pig [9], dog [10] and giant panda [11], which were determined by constructing BAC genomic library and physical map. The intact avian MHC genomic data were available from chicken [12], quail [13] and turkey [3] and all of them showed that the Galliform possessed a minimal essential MHC genomic structure spanning about one hundred kiolobases, which is so small that one BAC is enough to hold.…”

A physical map of a BAC clone contig covering the entire autosome insertion between ovine MHC Class IIa and IIb

“…To date, the majority of studies on the structure and organization of the ovine MHC have focused on the gene content and polymorphism of the class II region [18-23]. Although most loci in the sheep MHC are found to be homologous to their counterparts in the human MHC [12,21,24,25], there are significant differences. Examples of such differences include the DP loci in human being replaced by DY in sheep [19,21,26,27], and the number of DQA loci varying significantly among sheep breeds [20,22,28].…”