Typing Information
1996
Workshop Report
BoLA class II genes
Unlike man and mouse, the class II genes of cattle appear to be
divided between two distinct regions. The class IIa region contains
the DR and DQ genes, and is closely linked to the
class I region. RFLP analysis using human class II probes showed
that the class IIa region was separated by a recombination distance
of 17cM from the class IIb region containing DYA and DOB
( Andersson et al. 1988).
It was unclear, however, whether this indicated the presence of
a recombinational hot-spot, or a physical separation. Recent work,
using in situ hybridisation of large fragment clones mapped
a BoLA class I probe to BTA23q22, while a DYA probe hybridised
at BTA23q12-13 ( Skow et al. 1996a).
The physical distance that was detected appears to be sufficient
to account for the high recombination rate between the class IIa
and class IIb regions. Nevertheless, it does not exclude the possibility
of a recombinational hot-spot ( Park
et al. 1995).
Class
IIa region genes
The genes and products of the class IIa region have been extensively
studied because they represent the main class II restriction elements
and show a high degree of polymorphism. The DRA, DRB1, DRB2,
DRB3, DQA and DQB genes are located in the class IIa
region (Table 1; Davies et al.
1994b). Identical DRA sequences have been obtained
from one genomic and two cDNA clones ( van
der Poel et al. 1990; Aida et
al. 1994; Fraser et al. 1994),
but since three RFLP variants have been identified the DRA
gene may have limited polymorphism ( Andersson
et al. 1986b). The DRB1 gene is an unexpressed pseudogene,
and the DRB2 gene is poorly expressed ( Burke
et al. 1991; Russell et al.
1994b), but exhibits some polymorphism ( Muggli-Cockett
& Stone, 1991). DRB3 is expressed, highly polymorphic,
and encodes a functional restriction element ( Burke
et al. 1991; Fraser et al.
1996). One DRA allele, two DRB1 alleles, one
DRB2 allele, and 63 DRB3 alleles have been named
(Table 3).
The existence and polymorphism of the BoLA-DQ genes were
revealed by RFLP studies using human probes ( Andersson
et al. 1986a;
Sigurdardóttir et al. 1988; Teutsch
et al. 1990). In contrast to the DR genes, both DQA
and DQB genes are polymorphic, with 31 DQA and 26
DQB allelic RFLP patterns identified ( Davies
et al. 1994b). Use of exon-specific probes showed that the
DQA and DQB genes are duplicated in many haplotypes
( Andersson & Rask, 1988).
The duplication of DQB genes was confirmed by isolation
of two distinct genomic DQB-like sequences ( Groenen
et al. 1990; Stone & Muggli-Cockett,
1992). The subsequent isolation of cDNA sequences from duplicated
and unduplicated haplotypes showed that in several duplicated
haplotypes both DQB genes appeared to be expressed ( Xu
et al. 1991; 1994; Marello
et al. 1995).
Because the DQA and DQB sequences could not be reliably
assigned to distinct loci, the sequenced DQA and DQB
alleles have been given unique names but have not been assigned
to individual DQA or DQB loci. Locus assignments
will be made when the necessary mapping or full-length sequence
data become available. In this report 39 DQA and 37 DQB
alleles have been named (Table 4).
Class
IIb region genes
The class IIb region was defined on the basis of the large recombination
interval between the class IIa region and the DYA, DYB
and DOB genes (Andersson et al. 1988). The presence of
the class IIb region has been confirmed by further genetic and
physical mapping studies. These studies have shown that the DIB
and LMP2 genes are also located in the class Iib region
( Stone & Muggli-Cockett, 1993;
van Eijk et al. 1995; Shalhevet
et al. 1996; Skow et al. 1996).
Genomic clones representing parts of the DYA and DIB
genes have been cloned and sequenced ( van
der Poel et al. 1990; Stone
& Muggli-Cockett, 1990). Other BoLA genes which may reside
in this area, if synteny with the human and murine MHC regions
is conserved, are DNA, DMA, DMB, TAP and LMP7. There
is no evidence for expression of the DYA, DYB, DNA, DOB
and DIB genes. However, cDNA clones corresponding to the
DMA and DMB genes have been isolated ( Niimi
et al. 1995). One DIB allele, one DMA allele,
one DMB allele, and three DYA alleles have been
named (Table5).
